Monday, September 22, 2008

ATL/TV1102 Trial Results Presented at World Congress on Treatment and Research in Multiple Sclerosis




MELBOURNE, Australia and CARLSBAD, Calif., Sept 22, 2008 /PRNewswire-FirstCall via COMTEX News Network/ -- Antisense Therapeutics Ltd. (ASX: ANP) and Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) are pleased to advise that the results from the ATL/TV1102 Phase IIa clinical trial in patients with multiple sclerosis (MS) were presented Saturday at the World Congress on Treatment and Research in Multiple Sclerosis in Montreal, Canada by the Principal Investigator for the trial, Volker Limmroth, M.D., Ph.D., Chairman of the Department of Neurology, Cologne City Hospitals, Germany.

As previously reported, ATL/TV1102 significantly reduced disease activity in patients with Relapsing Remitting Multiple Sclerosis (RRMS) in a randomized, double-blind, placebo-controlled Phase II study designed to obtain evidence of ATL/TV1102's effectiveness in reducing MS-related brain lesions as detected by magnetic resonance images (MRI). The study met its primary endpoint showing a significant reduction by 54.4% (p=0.01) in cumulative number of new active lesions in the ATL/TV1102 treated patients compared to placebo. Further details on the study design and outcomes are provided in the conference abstract which follows this document.

Dr. Limmroth said, "As VLA-4 is a clinically validated target in MS, there is high interest in the potential application of treatment modalities directed against this target. In our study we were able to demonstrate, for the first time, that a second-generation antisense drug designed to specifically inhibit the production of VLA-4 could significantly reduce disease activity in RRMS patients as early as 8 weeks. The level of efficacy achieved by ATL/TV1102 is very promising particularly when considering the short duration of dosing within the trial. As an antisense drug ATL/TV1102 will have a different, potentially preferable, safety profile to other drugs that target VLA-4 and therefore presents an exciting future treatment option for RRMS patients."

Mark Diamond, Chief Executive Officer of Antisense Therapeutics, said, "We are delighted to have our ATL/TV1102 Phase IIa trial results presented at such an important scientific meeting on MS. The development of ATL/TV1102 as an MS treatment continues with our partner Teva Pharmaceutical Industries (Teva) and we look forward to the prospect of Teva reporting on ATL/TV1102's future clinical progress. Importantly, the demonstration of significant disease activity with ATL/TV1102 in MS points to the potential of ATL/TV1102 in other disease settings such as autoimmune, inflammation and cancer. It also provides important validation for the application of second-generation antisense drugs outside of cardiovascular and metabolic diseases such as high cholesterol and diabetes where there has been success to date. We believe our results provide important substantiation for the broader clinical application of the second-generation technology."

"We are very encouraged by the data. Not only do they represent promising results for patients with MS, but they also evidence the significant progress we are making in demonstrating the effectiveness, efficiency and the breadth of opportunity of our antisense platform. It's another disease and another tissue where we have great proof-of-concept for antisense drugs," said Stanley Crooke, M.D., Ph.D., Chairman and Chief Executive Officer of Isis. "ATL/TV1102 and ATL's strategic relationship with Teva to move the drug forward further validates our business strategy. ATL has successfully moved the drug forward and now has established a very experienced partner to complete development and commercialization of the drug. This strategy benefits patients as well as Isis' pipeline, platform and balance sheet."

The presentation has been webcasted and will be available on http://www.msmontreal.org/home/default_e.asp in the coming weeks. The Company will provide login details on its website http://www.antisense.com.au once these are confirmed.

Conference abstract follows:

VLA-4 Antisense - An Oligonucleotide targeting VLA-4 mRNA (ATL1102) significantly reduces new active lesions in patients with RR-MS

Volker Limmroth(1), Frederik Barkhof(2), Nuket Desem(3)

(1) Department of Neurology, Cologne City Hospitals, University of Cologne, Cologne, Germany, (2) Department of Radiology, MS Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands, (3) Antisense Therapeutics Ltd, Melbourne, VIC, Australia.

Background: Antisense oligonucleotides (ASOs) are an innovative new class of drugs that inhibit the expression of proteins by sequence-specific binding to the protein's mRNA. ATL1102 is a 2nd generation antisense inhibitor of CD49d, a subunit of Very Late Antigen 4 (VLA-4) which plays a key role in cell adhesion to vessel walls. VLA-4 blockade, as shown by monoclonal antibodies such as natalizumab, prevents activated lymphocytes from migrating into the CNS and significantly reduces disease activity in MS.

Objective: To evaluate VLA-4 Antisense (ATL1102) in the treatment of RR-MS

Methods: Randomized, double-blind, placebo-controlled multicenter Phase-IIa trial. 77 patients with RR-MS were treated for 8 weeks with either 200mg of ATL1102 or placebo subcutaneously twice weekly and evaluated for 16 weeks. MRI scans were performed at screening, and then monthly over 16 weeks. Primary efficacy variable: cumulative number of new active lesions (CNNAL; new gadolinium-enhancing T1 lesions (T1-Gd), new or enlarging T2 lesions) on MRIs taken at weeks 4, 8 and 12. Secondary efficacy variable: cumulative volume of T1-Gd lesions (CVT1L) on MRIs taken at weeks 4, 8 and 12.

Results: ITT population: 74 patients with a valid baseline MRI and at least one post-baseline MRI scan after first injection of study medication (n=39 placebo, n=35 ATL1102). ATL1102 showed a significant reduction, 54.4%, in CNNAL (6.2 placebo, 3.0 ATL1102; p=0.01). A reduction of 66.7% (p=0.002) was observed in the cumulative number (weeks 4,8,12) of new T1-Gd lesions with ATL1102. A reduction in CVT1L was also observed under ATL1102 but did not reach significance (589.4 mm3 placebo, 358.0 mm3 ATL1102; p=0.1068). Adverse events that were more frequent under ATL1102 included mild to moderate injection site reactions and a tendency for decreased platelet counts which were reversible after treatment interruption.

Conclusions: This proof-of-concept study of a drug designed to inhibit VLA-4 mRNA showed a significant reduction of the cumulative number of new active lesions in RR-MS patients following 8 weeks of treatment. These promising results warrant further investigation.

Background Information

ATL/TV1102 Phase IIa trial is a randomised, double-blind, placebo-controlled clinical trial of ATL/TV1102. Patients received either ATL/TV1102 or placebo injections over 8 weeks, and were monitored with monthly MRI (magnetic resonance imaging) brain scans during treatment, and for the 8 weeks following treatment. 77 patients were enrolled in the trial, which was conducted at multiple trial sites across six European countries.

Multiple sclerosis is a lifelong chronic disease of the central nervous system which is believed to affect as many as 2.5 million people worldwide. Global drug sales for MS are in excess of $US 6 billion and are expected to grow with the introduction of novel treatment options. There remains a high demand for more effective and better tolerated treatments.

About ATL/TV1102 for MS: ATL/TV1102 is an antisense drug discovered by Isis Pharmaceuticals, Inc. and licensed to ANP. Antisense drugs specifically block disease-causing proteins from being produced by interacting with their intended target based on information in the genetic code. ATL/TV1102 is a second-generation antisense inhibitor of CD49d, a subunit of VLA-4 (Very Late Antigen-4). In inflammation, white blood cells (leukocytes) move out of the bloodstream into the inflamed tissue, for example, the CNS in MS, and the lung airways in asthma. The inhibition of VLA-4 may prevent white blood cells from entering sites of inflammation, thereby halting progression of the disease. VLA-4 is a clinically validated target in the treatment of MS. Antisense inhibition of VLA-4 has demonstrated positive effects in a number of animal models of inflammatory disease including MS (Myers et al. J Neuroimmunol 160, p12-24, 2005).

About Antisense Therapeutics Limited: Antisense Therapeutics Limited (ASX: ANP) is an Australian publicly listed biopharmaceutical drug discovery and development company. Its mission is to create, develop and commercialize antisense pharmaceuticals for large unmet markets. ANP has two drugs in development and two drugs in pre-clinical research. ATL/TV1102 (injection) has completed a Phase IIa trial as a potential treatment of multiple sclerosis. ATL1103 is a second-generation antisense drug designed to lower blood IGF-I levels and is entering pre-clinical development as a potential treatment for acromegaly and vision disorders. ATL/TV1102 (inhaled) is at the pre-clinical research stage as a potential treatment for asthma. ATL1101 is a second-generation antisense drug at the pre-clinical research stage being investigated as a potential treatment for prostate cancer. ATL/TV1102 has been licensed to Teva Pharmaceutical Industries Ltd.

About Isis Pharmaceuticals, Inc.

Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The Company has successfully commercialized the world's first antisense drug and has 19 drugs in development. Isis' drug development programs are focused on treating cardiovascular and metabolic diseases. Isis' partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Ibis Biosciences, Inc., Isis' majority-owned subsidiary, is developing and commercializing the Ibis T5000(TM) Biosensor System, a revolutionary system to identify infectious organisms. Isis is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development and commercialization of microRNA therapeutics. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,500 issued patents worldwide. Additional information about Isis is available at http://www.isispharm.com.

Isis Forward-Looking Statement

This press release includes forward-looking statements regarding Isis' business, its drug discovery and development pipeline, and the therapeutic potential of ATL/TV1102 for the treatment of multiple sclerosis. Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement, including those statements that are described as Isis' goals. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such products. Isis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Isis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis' programs are described in additional detail in Isis' annual report on Form 10-K for the year ended December 31, 2007, and its most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from Isis.

Isis Pharmaceuticals is a registered trademark of Isis Pharmaceuticals, Inc. Ibis Biosciences and Ibis T5000 are trademarks of Ibis Biosciences, Inc. Regulus Therapeutics is a trademark of Regulus Therapeutics LLC.

SOURCE Isis Pharmaceuticals, Inc.; Antisense Therapeutics Ltd.

New data presented at WCTRIMS* supports the importance of early and sustained treatment with Betaseron®





Earlier treatment initiation and longer exposure to Betaseron was associated with improved long-term outcomes in multiple sclerosis

MONTREAL, CANADA, September 19, 2008 Data presented at the World Congress on Treatment and Research in Multiple Sclerosis (WCTRIMS) demonstrated that early initiation of Betaseron� (interferon beta-1b) treatment had a greater impact on long-term outcomes, when compared to delayed treatment.

The study, sponsored by Bayer HealthCare Pharmaceuticals, used data from the 16-Year Long-Term Follow-up Study of Betaseron to investigate the relationship between timing of drug initiation and length of exposure to treatment, and long-term outcomes. It demonstrated that initiating Betaseron treatment early in the disease reduced the risk of negative long-term outcomes, including conversion to secondary progressive multiple sclerosis (SPMS), reaching a confirmed EDSS of 6.0 or the use of a wheelchair. The study also found that the longer patients stayed on treatment, the better their long-term outcomes were.1

"The new analysis confirmed that in MS, timing of treatment is important. The findings showed that even if two patients are treated for an equivalent length of time, the one who started therapy earlier in the disease course had a better long-term outcome," said Douglas Goodin, MD, Director of the Multiple Sclerosis Center at UCSF Medical Center. "Patients and physicians should take these results into consideration when making treatment decisions."

A second study, called CogniMS, also presented at WCTRIMS, demonstrated that cognitive deficits can be measured early in the course of MS. The investigators suggested that such cognitive deficits may be clinically important for MS management decisions.

"Studies are now showing that apart from disease progression and relapse rates, cognition is another area that is impacted early in the course of the disease. In fact, there is a correlation between the level of disability at the start of treatment and cognitive function 16 years later. More research is needed to determine how treatment might benefit long-term cognitive outcome," said Dr. Goodin.

"The data presented here underscore the need to help patients start therapy earlier and stay on treatment for the long-term," said, Ludger Heeck, Ph.D. Vice President and General Manager, Specialty Medicine Bayer HealthCare Pharmaceuticals Inc. "Bayer is committed to helping provide both the medication and the support services that people need to help treat their MS. We pioneered the concept of customized MS support services, and our best-in-class BETAPLUSTM program goes far beyond treatment to offer a wide range of beneficial services for people with MS. From having dedicated MS nurses who can provide practical help and advice, to offering product enhancements like our new thinnest needle and optional autoinjector that can help make injection administration more comfortable, we continue to lead the way in helping people with MS start on and stay on treatment."

About the Trials
The 16-Year Long-term Follow-up Study is a multicenter observational study that collected data from patients with relapsing-remitting MS (RRMS) who participated in the pivotal North American trials for Betaseron. Several statistical methods were used to assess patient data and examine the relationship between timing of drug exposure and long-term outcomes. Drug exposure was measured as the medication possession ratio (MPR) defined as the actual time the patient received therapy divided by the total time possible before a negative outcome was reached (or at data censor). A statistical method called recursive partitioning was then used to divide treatment groups into "high" or "low" exposure and to determine the relationship between length of drug exposure and long-term outcomes. The use of MPR reduces the bias introduced in long-term trials by the tendency of patients who are doing well on therapy stay on therapy and for patients who are doing poorly to stop a particular therapy. Other statistical approaches including Propensity Scoring were used to control for other known sources of bias.1

CogniMS is a two-year observational study involving 1509 patients with early MS (diagnosed within two years) who were treated with Betaseron and assessed every six months using tests to measure cognition, fatigue and health-related quality of life. The trial includes patients from 32 countries2 and is currently ongoing.

About Betaseron
Betaseron is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis.

The most commonly reported adverse reactions are lymphopenia, injection-site reaction, asthenia, flu-like symptom complex, headache and pain. Gradual dose titration and use of analgesics during treatment initiation may help reduce flu-like symptoms. Betaseron should be used with caution in patients with depression. Injection-site necrosis has been reported in four percent of patients in controlled trials. Patients should be advised of the importance of rotating injection sites. Female patients should be warned about the potential risk to pregnancy. Cases of anaphylaxis have been reported rarely. See "Warnings," "Precautions," and "Adverse Reactions" sections of full Prescribing Information. More information, including the full Prescribing Information, is available at www.betaseron.com.

About Bayer HealthCare Pharmaceuticals Inc.
Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals business of Bayer HealthCare LLC, a subsidiary of Bayer AG. Bayer HealthCare is one of the world's leading, innovative companies in the healthcare and medical products industry, and combines the activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. Bayer HealthCare Pharmaceuticals comprises the following business units: Women's Healthcare, Diagnostic Imaging, General Medicine, which includes Cardiology and Primary Care and Specialty Medicine, which includes Hematology, Oncology and Multiple Sclerosis. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

Media Contact:
Marcy Funk
Bayer HealthCare Pharmaceuticals
973-305-5385

Forward-Looking Statements
This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our annual and interim reports to the Frankfurt Stock Exchange and in our reports filed with the U.S. Securities and Exchange Commission (including our Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

*WCTRIMS is the first joint meeting of ECTRIMS (the European Committee on Treatment and Research in Multiple Sclerosis) and its counterparts in North and Latin America: ACTRIMS and LACTRIMS

*DS Goodin, G Ebers, AT Reder, et al. Early Treatment with Interferon Beta-1b is Associated with Improved Long-Term Outcome in Multiple Sclerosis. World Congress on Treatment and Research in Multiple Sclerosis 2008.

*S Fredrikson, DW Langdon, K Kim, et al. Cognition, Fatigue, Depression and Health-Related Quality of Life in Early Multiple Sclerosis: Baseline Data from CogniMS, a Multinational Longitudinal Study. World Congress on Treatment and Research in Multiple Sclerosis 2008.

Glatiramer Acetate Decreases Severity of Relapsing-Remitting Multiple Sclerosis: Presented at WCTRMS




By Louise Gagnon

MONTREAL -- September 20, 2008 -- Glatiramer acetate has been shown to be efficacious in several outcomes among patients with relapsing-remitting multiple sclerosis (RRMS) when a scale other than the Expanded Disability Status Scale (EDSS) was used, according to research presented here at the World Congress on Treatment and Research in Multiple Sclerosis (WCTRMS).

A study of 251 patients was presented by investigator Joseph Herbert, MD, New York University, New York, New York, who described the EDSS as not truly reflective of clinical patient outcomes.

In the pivotal study, glatiramer acetate resulted in a 29% decrease in relapse rates compared with placebo. While patients treated glatiramer acetate did show improvement in their EDSS score, Dr. Herbert described the scale as an insufficiently sensitive measure of disease progression.

He presented the study findings in a poster session here on September 19

In this study, Dr. Herbert employed a Multiple Sclerosis Severity Score (MSSS) algorithm that relates MS disability as measured by EDSS to disease duration from the time of first symptom.

"This measure is a more useful outcome measure, because it corrects for certain flaws in the EDSS," said Dr. Herbert in an interview. "It accounts for duration of disease. The EDSS needs to be considered in the context of duration of disease."

This study enrolled patients who had EDSS scores of between 0 and 5. The researchers randomised 125 patients to subcutaneous injections of glatiramer acetate at 20 mg/day and 126 to placebo. Patients were followed for approximately 35 months.

Subjects in this study were divided into 6 groups according to their disease severity, explained Dr. Herbert. At study entry, the median MSSS scores for patients treated with glatiramer acetate and those treated with placebo were similar (4.59 vs 4.29; P = .1). At the end of the study, the median MSSS change from study entry was significantly greater in patients treated with glatiramer acetate compared with those treated with placebo (-0.73 vs -0.19; P = .0019).

With the revised grading of patients according to the MSSS, fewer patients who received glatiramer acetate were categorised as having severe disease. Specifically, more patients treated with glatiramer acetate were reclassified as having less severe illness (49% vs 31%) and fewer patients were reclassified as having more severe illness (16% vs 26%; P < .0014).

"There was a significant drop in severity for the treated patients," said Dr. Herbert. "There was a reassignment toward the higher grades with placebo patients."

The data support the use of the MSSS scale to measure changes in disability in patients with RRMS.

"We are suggesting that, since EDSS and duration of disease must be collected to begin with, that [MSSS] should be used as an outcome measure," said Dr. Herbert. "There is a true change in the intrinsic severity of the disease over 3 years, which is quite dramatic."

Funding for this study was provided by Teva Pharmaceutical Industries Ltd.

[Presentation title: Glatiramer Acetate Reduces Multiple Sclerosis Severity: Analysis of Patients From the US Pivotal Study Using the Multiple Sclerosis Severity Score. Abstract P454]

Vitamin D Levels Might Predict Risk for MS





FRIDAY, Sept. 19 (HealthDay News) -- Children with lower levels of vitamin D seem to be at a higher risk of being diagnosed with multiple sclerosis.

So say researchers who were expected to present the findings Friday at the World Congress on Treatment and Research in Multiple Sclerosis, in Montreal.

The idea fits nicely with previous research indicating that multiple sclerosis is more common the farther away you get from the equator, in other words, in areas where there is less sunlight.

Vitamin D synthesis is triggered when ultraviolet rays from the sun hit the skin. In addition, studies have also linked vitamin D with immune system function.

"In MS, the immune system is misregulated, and we do know that there's a susceptibility in the genes we inherit from our parents. We know that something triggers the disease," explained Patricia O'Looney, vice president of biomedical research at the National Multiple Sclerosis Society. "We know from epidemiological studies that there's a higher prevalence of MS the farther away you live from the equator and, more recently, we've learned that vitamin D does regulate the immune system."

"This is an interesting study of how environmental triggers and the immune system can be involved with MS, provided that one has these susceptibility genes," she added.

"Many studies have given us a good link between vitamin D status and immune function in MS," added study author Heather E. Hanwell, a doctoral candidate in nutritional sciences at the University of Toronto. "We wanted to see whether vitamin D status was lower in children who had their first demyelinating event and were subsequently diagnosed with MS."

A first demyelinating event is essentially an attack of symptoms that could indicate trouble with the central nervous system. One quarter of children who have such an attack go on to be diagnosed with MS.

The researchers measured levels of a vitamin D biomarker in children who had had a first event.

"The biomarker of vitamin D status was significantly lower in children diagnosed with MS to date," Hanwell said. "Children diagnosed with MS had lower vitamin D levels than those not diagnosed. Another way of looking at it, as vitamin D status increased, children had a lower risk of being diagnosed."

At this point, however, Hanwell believes the findings have more research than clinical implications.

"This type of work provides impetus for further research in this area, although, for a doctor, it would be important to look at vitamin D status in patients, particularly because 75 percent of our overall study group had vitamin D levels below what we considered to be optimal."

A second study also being presented at the World Congress found that the incidence of first demyelinating events increased by 9.2 percent for each higher degree of latitude up the eastern coast of Australia. The study was partially funded by the National Multiple Sclerosis Society, in the United States.

"There is growing evidence linking vitamin D and risk of MS," O'Looney said. "Further studies are certainly needed to see if vitamin supplementation could reduce the risk of MS. There is insufficient evidence that vitamin supplementation can influence the course of MS once it's begun."

More information

Visit the National Multiple Sclerosis Society for more on MS.

SOURCES: Patricia O'Looney, Ph.D., vice president, Biomedical Research, National Multiple Sclerosis Society, New York City; Heather E. Hanwell, doctoral candidate, department of nutritional sciences, University of Toronto

Tysabri PML patient deteriorates - researcher





By Reuters
September 19, 2008

BOSTON—One of two European patients, who developed a potentially deadly brain infection after taking the multiple sclerosis drug Tysabri, is deteriorating and likely to suffer brain damage, according to a researcher involved in their care.

The other patient diagnosed with the infection in July is recovering, the researcher said Friday.

The drug, made by Biogen Idec Inc and Elan Corp , was temporarily withdrawn from the market in 2005 after being linked with three cases of an often lethal infection known as progressive multifocal leukoencephalopathy, or PML.

Due to its advantages over older MS treatments and patient willingness to take on the risks, Tysabri was reintroduced with stricter warnings in 2006. No new cases were reported until the end of July, when Biogen announced that two patients had developed the infection.

Biogen said on Friday that no further new PML cases have been confirmed and its shares closed up 6 percent. Elan shares closed up more than 1 percent.

Dr. Ralf Gold of Ruhr University Bochum, Germany, said in an interview that a German patient, hospitalized near the town of Freiburg, is close to a coma and being fed through tubes, though he is breathing on his own.

The other patient, a 37-year-old Swede, is in a rehabilitation center near Stockholm and suffering only from mild weakness on one side of his body.

Gold said the 52-year-old German patient was not diagnosed until at least three months after developing the disease, whereas the Swedish patient's condition was identified in less than a month. As a result, the German patient had a higher level of the virus in his brain.

The two were treated through plasmapheresis, a procedure in which a patient's blood is removed, cleared of the drug, and replaced.

Gold presented an update on the two cases at the World Congress on Treatment and Research in Multiple Sclerosis in Montreal.

Investors have been watching the patients' progress to see whether PML can be reversed. They are also watching to see how many cases of the infection develop among patients taking the drug, which is considered a critically important growth driver for both companies.

Tysabri had second-quarter sales of $200 million, but its fortunes have been inextricably linked to PML concerns.

"The drug's strong efficacy profile should keep it as a preferred agent, in our opinion," Leerink Swann analyst William Tanner wrote in a research note.

In a report ahead of Gold's update, Geoff Porges, an analyst at Sanford Bernstein, said that if the disease becomes manageable through plasmapheresis then the impact of these cases will be blunted.

He said experts interviewed at the meeting have confirmed that in Europe and North America there are a number of patients with suspected PML whose physicians discontinued Tysabri use.

"We believe it is incumbent on Biogen to disclose this information to physicians in order for them to fully evaluate and disclose the risks associated with the product," he said.

Biogen spokeswoman Naomi Aoki said, "We have disclosed the only two cases of diagnosed PML that we have seen so far."

Gold added that while certain databases pick up cases in which a doctor suspects PML and discontinues Tysabri, the cases have not been confirmed either through an MRI or any other scientific measures.

Gold said the virus appears to be leaving the German patient's brain, but he is suffering from brain damage brought about by a condition known as immune reconstitution inflammatory syndrome, or IRIS. This occurs when the immune system, in eliminating an infection, produces an excessive inflammatory response that can worsen symptoms.

It is most likely the patient will be permanently brain damaged, Gold said. The only question is by how much.

The patient was started on a course of corticosteroids on Friday, the standard treatment for IRIS.

It typically becomes clear within a few days whether such a treatment is likely to work, Gold said. In the meantime, the patient is in a critical condition but not in intensive care.

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Laquinimod Demonstrated Significant and Sustained Impact on Multiple Sclerosis Disease Activity




New Crossover Data Presented at the World Congress on Treatment and Research in Multiple Sclerosis Shows Significant Reduction of Gadolinium-Enhancing Lesions

Jerusalem, Israel and Lund, Sweden, September 18, 2008 - New data from the extension phase of oral laquinimod in relapsing-remitting multiple sclerosis (RRMS) demonstrated a significant reduction in the mean number of gadolinium-enhancing (GdE) lesions in both patients who switched from placebo to laquinimod and patients who continued with their initial laquinimod dose.

In RRMS patients who switched from placebo to laquinimod, 52 percent reduction in the mean number of GdE lesions was observed (p<0.0007). The reduction was significant for both patients switching to high-dose (p<0.009) and low-dose laquinimod (p<0.03). In addition, the proportion of patients who switched to active treatment from placebo, and remained enhancing lesion-free, increased from 31 percent to 47 percent (p<0.012), further reinforcing the efficacy of laquinimod on magnetic resonance imaging (MRI) measured disease activity.

Patients initially treated with 0.6mg/day and 0.3mg/day during the double-blind trial remained on the same dose during the 36-week extension phase. An additional significant reduction in the mean number of GdE lesions was also observed in these patients (n=94, p=0.0062 and n=80, p=0.0013, respectively), a high proportion of which remained completely free of GdE lesions, demonstrating the sustained effect of laquinimod on MRI disease activity.

"These latest data show the rapid onset and sustainability of laquinimod efficacy in MS patients," said Giancarlo Comi, M.D., University Vita-Salute San Raffaele, Scientific Institute San Raffaele, Milan, Italy, principal investigator of the study. "Just as exciting is the fact that, with increased number of patients exposed to laquinimod, we found no new risks or safety issues. This reinforces earlier results demonstrating the laquinimod safety profile. The MS community looks forward to future data as we continue enrolling patients in the laquinimod Phase III clinical program."

These new data from the extension study build upon the initial 36-week, Phase IIb study results published in The Lancet*, which demonstrated that once-daily, oral 0.6mg laquinimod significantly reduced MRI disease activity by a median of 60 percent, compared to placebo, and was well tolerated.

Teva is currently enrolling patients for Allegro and Bravo, two pivotal Phase III clinical trials of laquinimod. For more information please visit www.TevaClinicalTrials.com.

*Lancet 2008; 371:2085-92

About the Study
In the study, "Oral laquinimod in patients with relapsing�remitting multiple sclerosis: 36 weeks double-blind active extension of the multi-center, randomized, double-blind, parallel-group placebo-controlled study," subjects originally assigned to placebo were equally randomized to receive either 0.3 or 0.6mg/day laquinimod, while others continued their original treatment for a 36-week, double-blind extension. Magnetic resonance imaging (MRI) was performed at the beginning and at the end of the active extension phase. The mean number of GdE lesions in patients who switched from placebo to laquinimod was reduced by 52 percent (from 4.46�6.55 to 2.12�3.73; p<0.0007) from the time patients began receiving active treatment.

Two hundred and fifty seven patients (91 percent) entered the extension phase to receive laquinimod 0.3mg/day or 0.6mg/day. Neither new safety signals nor an increase in the incidence rate of adverse events and laboratory abnormalities have emerged following new or prolonged exposure to laquinimod.

Patients on continuous 18 month laquinimod 0.6mg treatment continued to show low MRI disease activity, with a high proportion remaining free of GdE-lesions. A good tolerability profile was also observed. Treatment effects on MRI activity witnessed during the placebo-controlled phase were reproduced when placebo patients switched to laquinimod.

About Multiple Sclerosis
Multiple Sclerosis (MS) is the leading cause of neurological disability in young adults. It is estimated that more than 400,000 people in the United States are affected by the disease and that two million people may be affected worldwide. MS is a progressive, demyelinating disease of the central nervous system affecting the brain, spinal cord and optic nerves. Demyelination is the destructive breakdown of the fatty tissue that protects nerve endings.

About Laquinimod
Laquinimod is a novel once-daily, orally administered immunomodulatory compound that is being developed as a disease-modifying treatment for RRMS. Active Biotech developed laquinimod and licensed it to Teva Pharmaceutical Industries, Ltd. in June 2004. A Phase IIb study in 306 patients was recently published in The Lancet and demonstrated that an oral 0.6 mg dose of laquinimod, administered daily, significantly reduced MRI disease activity by a median of 60 percent versus placebo in RRMS patients. In addition, the study showed a favorable trend toward reducing annual relapse rates and the number of relapse-free patients compared with placebo. Treatment was well tolerated, with only some transient and dose-dependent increases in liver enzymes reported. Over 480 MS patients have received laquinimod in various clinical trials.

In addition to the efficacy that laquinimod has shown in Phase II RRMS clinical trials, laquinimod has demonstrated potent therapeutic efficacy in preclinical models of other autoimmune diseases such as rheumatoid arthritis, insulin-dependent diabetes mellitus, Guillain Barr� Syndrome, lupus and Inflammatory Bowel Disease. The broad profile of efficacy in animal models of inflammatory diseases suggests that laquinimod affects a pivotal pathway of inflammation and autoimmunity. Teva expects to initiate the clinical development of laquinimod for Crohn's disease and Lupus Nephritis in the near future.

About the Phase III Program
Allegro (assessment of oral laquinimod in preventing progression of MS) is a pivotal, global, 24/30-month, double-blind, Phase III study designed to evaluate the efficacy, safety and tolerability of laquinimod versus placebo in the treatment of RRMS. The enrollment goal is approximately 1,000 patients with RRMS.

Bravo (benefit-risk assessment of Avonex® and laquinimod) is a pivotal, multinational, multi-center, randomized, double-blind, parallel-group, placebo-controlled study designed to compare the safety and efficacy of laquinimod with placebo and to provide risk-benefit data for laquinimod versus a currently available injectable treatment. The enrollment goal is approximately 1,200 patients with RRMS.

The globally conducted clinical program will include centers throughout the United States as well as centers Canada, Europe, and Israel. To learn more about the research please visit www.TevaClinicalTrials.com or call 1-866-550-0614 (Allegro) or 1-800-840-5601 (Bravo).

About Active Biotech
Active Biotech AB (OMX NORDIC: ACTI), headquartered in Sweden, is a biotechnology company with R&D focus on autoimmune/inflammatory diseases and cancer. Projects in pivotal phase are laquinimod, an orally administered small molecule with unique immunomodulatory properties for the treatment of multiple sclerosis, as well as ANYARA for use in cancer targeted therapy, primarily renal cancer. Further key projects in clinical development comprise the three orally administered compounds TASQ for prostate cancer, 57-57 for SLE and RhuDex® for RA. Please visit www.activebiotech.com for more information.

About Teva
Teva Pharmaceutical Industries Ltd., headquartered in Israel, is among the top 20 pharmaceutical companies in the world and is the world's leading generic pharmaceutical company. The Company develops, manufactures and markets generic and innovative human pharmaceuticals and active pharmaceutical ingredients, as well as animal health pharmaceutical products. Over 80 percent of Teva's sales are in North America and Europe.

Teva's Safe Harbor Statement under the U. S. Private Securities Litigation Reform Act of 1995:
This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements are based on management's current beliefs and expectations and involve a number of known and unknown risks and uncertainties that could cause our future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to: our ability to successfully develop and commercialize additional pharmaceutical products, the introduction of competing generic equivalents, the extent to which we may obtain U.S. market exclusivity for certain of our new generic products and regulatory changes that may prevent us from utilizing exclusivity periods, competition from brand-name companies that are under increased pressure to counter generic products, or competitors that seek to delay the introduction of generic products, the impact of consolidation of our distributors and customers, potential liability for sales of generic products prior to a final resolution of outstanding patent litigation, including that relating to the generic versions of Allegra®, Neurontin®, Lotrel® and Protonix®, the effects of competition on our innovative products, especially Copaxone® sales, the impact of pharmaceutical industry regulation and pending legislation that could affect the pharmaceutical industry, the difficulty of predicting U.S. Food and Drug Administration, European Medicines Agency and other regulatory authority approvals, the regulatory environment and changes in the health policies and structures of various countries, our ability to achieve expected results though our innovative R&D efforts, our ability to successfully identify, consummate and integrate acquisitions, including the pending acquisition of Barr Pharmaceuticals Inc., potential exposure to product liability claims to the extent not covered by insurance, dependence on the effectiveness of our patents and other protections for innovative products, significant operations worldwide that may be adversely affected by terrorism, political or economical instability or major hostilities, supply interruptions or delays that could result from the complex manufacturing of our products and our global supply chain, environmental risks, fluctuations in currency, exchange and interest rates, and other factors that are discussed in this report and in our other filings with the U.S. Securities and Exchange Commission ("SEC").



Company Contacts:
Elana Holzman
Kevin Mannix

Teva Pharmaceutical Industries Ltd.
Teva North America

972 (3) 926-7554
(215) 591-8912

Copaxone® Demonstrated Protective Effect in Patients with Clinically Isolated Syndrome Suggestive of Multiple Sclerosis




PreCISe Data Presented at World Congress on Treatment and Research in Multiple Sclerosis

Jerusalem, Israel, September 19, 2008 - New data from PreCISe, in clinically isolated syndrome patients, have demonstrated that COPAXONE® (glatiramer acetate injection) significantly improved neuro-axonal integrity in patients presenting with a first clinical event suggestive of multiple sclerosis (MS) versus patients who received placebo (p=0.03), as measured by proton magnetic resonance spectroscopy (MRS). This effect was maintained over two years of treatment.

The data represent the first evidence of neuro-axonal protection by a disease modifying therapy in patients presenting with a first clinical event suggestive of MS.

Data were derived from an ancillary study from the Phase III, randomized, placebo-controlled PreCISe trial, which demonstrated that patients treated with COPAXONE® (n=243) had a 45 percent reduction in the risk of developing clinically definite multiple sclerosis (CDMS) compared to those on the placebo (n=238).

"These newly announced data, so far shown in RRMS patients treated with COPAXONE®, provide more evidence that treatment may control the neuronal damage associated with MS disease pathology," said Douglas Arnold, M.D., Professor of Neurology, McGill University and the primary investigator of this ancillary study. "The PreCISe trial demonstrated a significant benefit of COPAXONE® on both clinical and MRI disease activity, along with further reinforcing the excellent safety profile."

The data were presented along with two other presentations from the PreCISe study at the World Congress on Treatment and Research in Multiple Sclerosis, in Montreal, Canada. Additional data derived from the PreCISe study demonstrated that COPAXONE® significantly delayed time to conversion to CDMS and reduced magnetic resonance imaging (MRI) disease activity. The effect was robust among the PreCISe study population (n=481), as a whole and also in subgroups of patients (segmented by gender, age, type of unifocal manifestation as well as steroid treatment for the initial attack, and MRI findings at study baseline). Based on these data, applications for marketing authorization for the extension of its indication to include the treatment of patients with a first clinical event suggestive of MS were submitted in Europe and in the U.S. and are currently under review.

About the PreCISe Data
The study, "Treatment with glatiramer acetate protects axons in patients with clinically isolated syndromes: evidence from the PreCISe trial," determined that patients with clinically isolated syndrome (CIS) who received COPAXONE® showed improvement in their cerebral neuro-axonal integrity relative to patients treated with placebo.

Proton MRS was performed in a subgroup of patients in the PreCISe trial (n=34) to measure the concentration of N-acetulaspartate (NAA) levels. NAA/CR measurements were acquired each year from each patient enrolled at 10 clinical sites in seven countries. Patients terminated at the time of relapse.

Patients who received COPAXONE® showed significant improvement in their cerebral neuro-axonal integrity compared to patients treated with placebo, who showed the decline expected from natural history studies. Paired changes in NAA/CR ratio differed significantly between both patients treated with COPAXONE® (+0.14, n=11) compared to those treated with placebo (-0.33, n=9, p=0.03) at one year, and the change maintained at two years (COPAXONE® n=6, +0.17; placebo n=3, -0.23, p=0.15).

Previously announced PreCISe studies included:

"Treatment with glatiramer acetate reduces MRI-detectable disease activity in patients at presentation with CIS suggestive of MS"

* Demonstrated that early treatment with COPAXONE® is effective in both delaying time to conversion to CDMS and reducing MRI activity in patients presenting with CIS


"Treatment with glatiramer acetate delays conversion to CDMS in patients with CIS: subgroup analyses"

* Demonstrated that COPAXONE® treatment effect was robust among the PreCISe study population (n=481) as a whole ,as well as in subgroups of patients (broken down by gender, age and type of unifocal manifestation and steroid treatment for the initial attack, and MRI findings at study baseline)



About COPAXONE®
COPAXONE® is indicated for the reduction of the frequency of relapses in RRMS. The most common side effects of COPAXONE® are redness, pain, swelling, itching, a lump or an indentation at the site of injection, weakness, infection, pain, nausea, joint pain, anxiety, and muscle stiffness.

COPAXONE® is now approved in 51 countries worldwide, including the United States, Canada, Mexico, Australia, Israel, and all European countries. In North America, COPAXONE® is marketed by Teva Neuroscience, Inc., which is a subsidiary of Teva Pharmaceutical Industries Ltd. (NASDAQ:TEVA). In Europe, COPAXONE® is marketed by Teva Pharmaceutical Industries Ltd. and sanofi-aventis. COPAXONE® is a registered trademark of Teva Pharmaceutical Industries Ltd.

See additional important information at http://www.copaxone.com/pi/index.html or call 1-800-887-8100 for electronic releases. For hardcopy releases, please see enclosed full prescribing information.

About Teva
Teva Pharmaceutical Industries Ltd., headquartered in Israel, is among the top 20 pharmaceutical companies in the world and is the world's leading generic pharmaceutical company. The Company develops, manufactures and markets generic and innovative human pharmaceuticals and active pharmaceutical ingredients, as well as animal health pharmaceutical products. Over 80 percent of Teva's sales are in North America and Europe.

Teva's Safe Harbor Statement under the U. S. Private Securities Litigation Reform Act of 1995:

This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements are based on management's current beliefs and expectations and involve a number of known and unknown risks and uncertainties that could cause our future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to: our ability to successfully develop and commercialize additional pharmaceutical products, the introduction of competing generic equivalents, the extent to which we may obtain U.S. market exclusivity for certain of our new generic products and regulatory changes that may prevent us from utilizing exclusivity periods, competition from brand-name companies that are under increased pressure to counter generic products, or competitors that seek to delay the introduction of generic products, the impact of consolidation of our distributors and customers, potential liability for sales of generic products prior to a final resolution of outstanding patent litigation, including that relating to the generic versions of Allegra® , Neurontin®, Lotrel® and Protonix®, the effects of competition on our innovative products, especially Copaxone® sales, the impact of pharmaceutical industry regulation and pending legislation that could affect the pharmaceutical industry, the difficulty of predicting U.S. Food and Drug Administration, European Medicines Agency and other regulatory authority approvals, the regulatory environment and changes in the health policies and structures of various countries, our ability to achieve expected results though our innovative R&D efforts, our ability to successfully identify, consummate and integrate acquisitions, including the pending acquisition of Barr Pharmaceuticals Inc., potential exposure to product liability claims to the extent not covered by insurance, dependence on the effectiveness of our patents and other protections for innovative products, significant operations worldwide that may be adversely affected by terrorism, political or economical instability or major hostilities, supply interruptions or delays that could result from the complex manufacturing of our products and our global supply chain, environmental risks, fluctuations in currency, exchange and interest rates, and other factors that are discussed in this report and in our other filings with the U.S. Securities and Exchange Commission ("SEC").



Company Contacts:
Company Contacts:
Elana Holzman
Kevin Mannix

Teva Pharmaceutical Industries Ltd.
Teva North America

972 (3) 926-7554
(215) 591-8912

Biogen Idec MS pill found to slow damage




Bloomberg News / September 19, 2008


NEW YORK - Biogen Idec Inc.'s experimental pill to treat multiple sclerosis prevented brain lesions associated with the disease from getting worse, a study found.

The pill, called BG-12, reduced the conversion of new spots of inflammation into permanent damage in a trial of 56 patients, Biogen said yesterday at the World Congress on Treatment and Research in Multiple Sclerosis in Montreal.

In MS, neurons are stripped of an insulating coating known as myelin by the immune system, causing the cells to malfunction. That leads to MS symptoms such as muscle weakness and loss of coordination, according to the Mayo Clinic. Biogen has received approval from US regulators to speed the review process for its pill, the company said yesterday. If cleared for sale in the United States, BG-12 could be the first oral medication for MS patients to reach the market.

"There are two elements: You want to keep the lesions from forming in the first place and then, even if a lesion developed, you want to know the damage is reduced, and that's what you're seeing," said Mike Panzara, the chief medical officer for Cambridge, Mass.-based Biogen in a telephone interview yesterday. "Even if a lesion does develop on BG-12, injury is less because it's less often the lesions become permanent."

About 29 percent of the lesions in the brains of patients on BG-12 turned into signs of permanent damage, compared with 44 percent of those in the placebo group, the study showed.

The company began final-stage testing on BG-12 in January. The trials, on more than 2,000 patients with a recurring form of the disease, will last two years. The drug is being compared with a placebo and with Teva Pharmaceutical Industries' Copaxone, an approved treatment for the disease.

Biogen Idec sells the MS drugs Avonex, which is given as a once-a-week injection, and Tysabri, an infusion given once a month in a doctor's office or hospital clinic. About 1 million people worldwide suffer from MS.

© Copyright 2008 Globe Newspaper Company.

Merck Serono Announces Initiation of the ORACLE MS Trial to Evaluate Cladribine Tablets in Patients at Risk of Developing Multiple Sclerosis




• ORACLE MS Phase III trial will assess effectiveness of cladribine tablets in preventing conversion to definite multiple sclerosis in addition to the fully enrolled Phase III pivotal trial – the CLARITY study – for treatment of relapsing forms of multiple sclerosis

Geneva, Switzerland, September 18, 2008 – Merck Serono, a division of Merck KGaA, Darmstadt, Germany, announced today the initiation of a Phase III trial to evaluate the therapeutic effects of its proprietary oral formulation of cladribine (cladribine tablets) in patients at risk of developing multiple sclerosis (MS).

The trial, called ORACLE MS (ORAl CLadribine in Early MS) will evaluate the safety and efficacy of two dosage regimens of cladribine tablets versus placebo in the treatment of patients who have experienced a first clinical event suggestive of MS. Cladribine tablets are currently also being evaluated in a fully enrolled Phase III pivotal trial – the CLARITY1 study – for treatment of relapsing forms of MS. As announced in January 2007, CLARITY was the first pivotal trial among all Phase III oral compounds in development for MS to complete enrollment. Cladribine tablets have been granted a fast track designation by the US Food and Drug Administration.

“There is increasing evidence supporting the initiation of treatment with a disease-modifying drug in patients who have experienced a first clinical event suggestive of multiple sclerosis, an initial stage of the disease when clinical manifestations are not necessarily pronounced but where the potential exists for irreversible neurological damage to take place,” said Dr. Thomas Leist, Associate Professor of Neurology and Director of the Comprehensive MS Center at Thomas Jefferson University, Philadelphia, PA, and an investigator in the ORACLE MS study. “The ORACLE MS study will evaluate the effectiveness and safety of cladribine tablets in preventing conversion to definite multiple sclerosis.”

“As a leader in multiple sclerosis treatments, we are committed to providing new options that can further improve the course of the disease and the quality of life for people living with this disease,” said Dr. Richard Douge, Executive Vice President, Global Marketing, Merck Serono. “The initiation of the ORACLE MS study further demonstrates our commitment to continue to build a solid portfolio of products for use in a broad multiple sclerosis patient population. We believe that our proprietary oral formulation of cladribine has the potential to address an important unmet medical need at a critical time of disease development.”

The ORACLE MS study is a randomized, double-blind, placebo-controlled, international trial. It will involve more than 600 patients considered at risk of developing MS due to a recently experienced isolated demyelinating event (e.g. optic neuritis, myelopathy or brainstem syndrome) and having MRI brain scans consistent with early signs of MS. Study participants will be randomized in one of the three arms of the study to receive one of two different dosage regimens of cladribine tablets or matching placebo tablets (1:1:1 ratio).

Patients will be treated for a period of two years (96 weeks), or up to the time when they experience a second attack leading to a diagnosis of clinically definite MS, in which case they would be offered open-label treatment with Rebif® 44 mcg three times a week for a 96-week maintenance treatment period. Patients who do not convert to clinically definite MS within the initial 96-week period of the study will be eligible to enroll in a 96-week long-term follow-up treatment period. These maintenance and long-term follow-up periods of the study are intended to assess the effect of early treatment with cladribine tablets on relapses and subsequent treatment response to disease-modifying therapy for relapsing-remitting MS and to evaluate the sustained effect of cladribine tablets in delaying the development of definite MS.

In the study, cladribine tablets are given in two or four treatment cycles in the first year, with each cycle consisting of once daily administration for four to five consecutive days, which means study patients take cladribine tablets for only 8 to 20 days during that year. In the second year, two treatment cycles are administered to all patient groups.

The primary endpoint of the ORACLE MS trial is time to conversion to MS, according to the McDonald criteria. Other endpoints include time to conversion to clinically definite MS according to the Poser criteria (the main secondary endpoint), assessments of MRI brain scans, and disability progression.

Approximately 200 medical centers globally are expected to participate in this trial.
1 CLARITY: CLAdRIbine Tablets Treating MS OrallY

About cladribine tablets

Merck Serono’s proprietary oral formulation of cladribine is currently being evaluated in Phase III as a treatment for patients with relapsing forms of multiple sclerosis (MS). Cladribine is a small molecule that may interfere with the behavior and the proliferation of certain white blood cells, particularly lymphocytes, which are thought to be involved in the pathological process of MS.

About Rebif®

Rebif® (interferon beta-1a) is a disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS) and is similar to the interferon beta protein produced by the human body. The efficacy of Rebif® in chronic progressive MS has not been established. Interferons are thought to help modulate the body’s immune system and reduce inflammation. The exact mechanism is unknown.

Rebif®, which was approved in Europe in 1998 and in the US in 2002, is registered in more than 80 countries worldwide. Rebif® has been proven to delay the progression of disability, reduce the frequency of relapses and reduce MRI lesion activity and area*. Rebif® is available in a 22 microgram and 44 microgram ready-to-use pre-filled syringe and a titration pack (8.8 micrograms).

Rebif® should be used with caution in patients with a history of depression, liver disease and seizures. Most commonly reported side effects are flu-like symptoms, injection site disorders, elevation of liver enzymes and blood cell abnormalities. Patients, especially those with depression, seizure disorders, or liver problems, should discuss treatment with Rebif® with their doctors. For more information about Rebif®, please visit www.mslifelines.com for prescribing information.

* The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.

About Merck Serono and multiple sclerosis

Merck Serono is a leader in multiple sclerosis (MS) with Rebif® (interferon beta-1a), a disease-modifying drug used to treat relapsing forms of MS, which is registered in more than 80 countries worldwide. Full prescribing information for this product can be obtained by contacting the Company or visiting its website. Additional therapeutic options are currently under development at Merck Serono, including cladribine tablets, currently in Phase III and potentially the first oral therapy for MS, as well as several products in early stage development. Merck Serono also is taking a leading role in developing an understanding of the role of genetics in MS.
About multiple sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory condition of the nervous system and is the most common, non-traumatic, disabling neurological disease in young adults. The World Health Organization estimates that up to 2.5 million people suffer from MS worldwide. While symptoms can vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs and problems with strength and coordination. The relapsing forms of MS are the most common.

About Merck Serono

Merck Serono is the division for innovative prescription pharmaceuticals of Merck, a global pharmaceutical and chemical group. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. Its North American business operates in the United States and Canada as EMD Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux®), multiple sclerosis (Rebif®), infertility (Gonal-f®), endocrine and cardiometabolic disorders (Glucophage®, Concor®, Euthyrox®, Saizen®, Serostim®), as well as psoriasis (Raptiva®).
With an annual R&D expenditure of around € 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in autoimmune and inflammatory diseases.

About Merck

Merck is a global pharmaceutical and chemical company with total revenues of € 7.1 billion in 2007, a history that began in 1668, and a future shaped by 31,946 employees in 60 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

For more information, please visit www.merckserono.net or www.merck.de

Avigen Completes Multi-Center AV650 Phase 2b Spasticity Trial in Patients With Multiple Sclerosis




Top Line Data Expected in Q4 2008

ALAMEDA, Calif., Sep 18, 2008 (GlobeNewswire via COMTEX News Network) -- Avigen, Inc. (Nasdaq:AVGN), a biopharmaceutical company innovating therapeutics for neurological care, today announced the completion of the double-blind portion of its Phase 2b trial for AV650 (tolperisone HCl) in the treatment of spasticity associated with multiple sclerosis (MS). This Phase 2b spasticity trial is evaluating the safety, tolerability and efficacy of AV650 in MS patients at doses up to 900mg/day for one month followed by an open-label safety extension. The trial is being conducted in top MS centers in Germany and several other European countries.

"The completion of this trial in less than a year marks a significant milestone for the AV650 program and Avigen," said Kenneth Chahine, Ph.D., J.D., Avigen's President and Chief Executive Officer. "The rapid enrollment further supports the need for new and non-sedating agents to treat spasticity, and we have confidence that our planned Phase 3 trials can be completed in a similar timeframe. While the blinded portion of the trial is complete and will report before the end of 2008, more than 90% of the patients have elected to participate in the on-going open-label extension and will continue to receive AV650 for up to an additional twelve months."

Avigen is developing AV650 for commercialization in the North American market for the treatment of disabling neuromuscular spasticity and spasm under a license and supply agreement with Sanochemia Pharmazeutika AG, Vienna, Austria. AV650 is considered a New Chemical Entity (NCE) in the United States.

Tolperisone is an orally administered, centrally acting small molecule marketed for the treatment of neuromuscular spasticity and spasm in Europe and Asia. Avigen's U.S. development program is designed to build on the extensive ex-U.S. safety and efficacy experience with this compound. Versions of tolperisone have been approved for marketing in Germany for over 10 years. Sanochemia and its European marketing partner, Orion Pharma, currently market a proprietary 150mg tablet formulation of tolperisone in Germany under the brand name Viveo(r).

Spasticity is considered one of the main symptoms of the more than 2.5 million people with MS worldwide, affecting up to 60% of this population. Randall Schapiro, M.D, Director of The Schapiro Center for Multiple Sclerosis at the Minneapolis Clinic of Neurology and Clinical Professor of Neurology at the University of Minnesota, commented, "MS patients must cope with significant side effects from currently available treatments for spasticity, including drowsiness, fatigue and cognitive impairment. These side effects do affect their quality of life. We recognize the need for better-tolerated, non-sedating therapies in the United States, and we are encouraged by the European experience of tolperisone."

About the Trial

This double-blind, randomized clinical trial is being conducted in 27 MS centers in Germany and other European countries. It will evaluate safety, tolerability, pharmacokinetics and efficacy in up to 150 MS patients suffering from spasticity. This trial is being conducted to Good Clinical Practice standards by a leading international contract research organization. Following a four-week double blind assessment, patients are offered the opportunity to continue for up to twelve months in an open-label safety phase. The primary efficacy endpoint is the Ashworth scale, a standard tool used in the clinic to measure increased movement. Secondary endpoints include Brief Pain Index (BPI), painful spasm diaries, and clinical impression of change.

About Neuromuscular Spasm and Spasticity

Chronic or recurrent muscle spasm is a sudden, violent, painful contraction of muscles typically associated with serious neurological disorders such as Lou Gehrig's disease (ALS), multiple sclerosis, stroke, spinal cord injury, and cerebral palsy. These painful muscle spasms are often, but not always, associated with spasticity, an abnormality in muscle "tone." Spastic limbs become stiff and rigid because the muscles fail to relax, lacking normal regulation by the damaged nervous system. Both spasticity and sudden, painful muscle spasms can occur as complications of the neurological disorders mentioned above. Spasticity is a common symptom in multiple sclerosis, which affects 2.5 million worldwide.

About Avigen

Avigen is a biopharmaceutical company focused on developing and commercializing small molecule therapeutics to treat serious neurological disorders, including neuropathic pain and neuromuscular spasm and spasticity. Avigen's strategy is to complete the requirements of clinical development for each of the candidates in its product pipeline, and continue to look for opportunities to expand its pipeline through a combination of internal research, acquisitions, and in-licensing, with the goal of becoming a fully integrated commercial biopharmaceutical company that remains committed to its neurology products. Avigen is currently developing AV650 for spasticity and neuromuscular spasm and AV411 for neuropathic pain, as well as opioid withdrawal and addiction in collaboration with the National Institute of Drug Abuse. Additionally, the company is advancing AV513, a novel therapy for the treatment of multiple bleeding disorders, including hemophilia A and B, toward clinical trials. For more information about Avigen, consult the company's website at www.avigen.com.
Statement under the Private Securities Litigation Reform Act

The statements in this press release relating to Avigen's expectations regarding the timely and reliable completion of its clinical trials, its expectations regarding reporting AV650 Phase 2 top-line data in the fourth quarter of 2008, its expectations regarding initiating and completing planned Phase 3 clinical trials in a similar timeframe to the Phase 2b spasticity trial in patients with MS, and its goal of becoming a fully integrated commercial biopharmaceutical company remaining committed to its neurology products are forward-looking statements. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others, the fact that development of small molecule therapeutics and other therapeutic discovery and development is a time- and resource-intensive process, which may result in the expenditure of a significant amount of time and resources with no progress towards clinical trials or marketable product resulting from the effort; the risk that Avigen will not be able to obtain regulatory approvals for its drug products, which is required prior to marketing drug products; and the risk that early positive preclinical and clinical results will not guarantee that the potential products will ultimately be effective in treating the indications for which they are developed, or exhibit the unique properties they appear to possess. In addition, there are many other risks and uncertainties inherent in the development of drug products. Other risks and uncertainties relating to Avigen are detailed in reports filed by Avigen with the Securities and Exchange Commission, including Avigen's Quarterly Report on Form 10-Q for the period ended June 30, 2008, under the caption "Risks Related to Our Business" in Item 2 of Part I of that report, which was filed with the SEC on August 11, 2008.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Avigen, Inc.

Avigen, Inc.
Michael Coffee, Chief Business Officer
510-748-7372
Fax: 510-748-7155
1301 Harbor Bay Parkway
Alameda, CA 94502

MS rates higher farther from equator, atlas shows




Multiple sclerosis is more common among people living in northern latitudes, but they aren't the only ones affected, according to a new report.

The World Health Organization and the London-based Multiple Sclerosis International Federation published the MS Atlas on Wednesday. It summarizes information on the disease in 112 countries, none of which were free of the disease.

MS is a neurodegenerative disease that attacks the brain and spinal cord, and can lead to paralysis and sometimes blindness.

Some people with MS experience little disability during their lifetime. But up to 60 per cent are no longer fully able to walk 20 years after onset, which has major implications for their quality of life and costs to society, the report said. Symptoms appear around 30 years of age on average.

“The Atlas of MS reveals how these implications impact women more than men, by at least two to one, at an age when they are starting a family and developing a career,” said Dr. Benedetto Saraceno, director of the WHO's department of mental health and substance dependence.

The study confirms that MS is a global disease, not solely of the more developed “northern” and “western” countries, the report said.

In Canada alone, the economic impact totals more than $1 billion annually, according to the Multiple Sclerosis Society of Canada.

Countries reporting the highest estimated prevalence, or total number of cases of MS at a particular point in time, were:

* Hungary at 176 per 100,000
* Slovenia 150 per 100,000.
* Germany 149 per 100,000.
* United States 135 per 100,000.
* Canada 132.5 per 100,000.
* Czech Republic 130 per 100,000.
* Norway 125 per 100,000.
* Denmark 122 per 100,000.
* Poland 120 per 100,000.
* Cyprus 110 per 100,000.

Countries reporting the highest estimated incidence or estimated number of new cases of MS were:

* Croatia 29 per 100,000.
* Iceland 10 per 100,000.
* Hungary 9.8 per 100,000.
* Slovakia 7.5 per 100,000.
* Costa Rica 7.5 per 100,000.
* United Kingdom 6.0 per 100,000.
* Lithuania 6.0 per 100,000.
* Denmark 5.9 per 100,000.
* Norway 5.5 per 100,000.
* Switzerland 5.0 per 100,000.

"Typically, our results confirmed the well established suggestion that there are strong geographical patterns to the disease and that the frequency of MS varies by geographical region throughout the world, increasing with distance from the equator in both hemispheres," the report said.

Low- and middle-income countries showed a lack of services and resources to care for people with MS. Poorer countries also had fewer diagnostic tools such as MS scanners, which means the disease is likely underrecorded in developing countries.

The atlas also compares how North and South America, Europe, Asia, Eastern Mediterranean and African countries offer resources to diagnose, treat, rehabilitate and support people with the MS.

NEW LONG-TERM DATA SHOW THAT PATIENTS TAKING AVONEX® FOR UP TO 15 YEARS EXPERIENCE REDUCED DISABILITY PROGRESSION AND IMPROVED QUALITY OF LIFE


NEW LONG-TERM DATA SHOW THAT PATIENTS TAKING AVONEX® FOR UP TO 15 YEARS EXPERIENCE REDUCED DISABILITY PROGRESSION AND IMPROVED QUALITY OF LIFE

MONTREAL, CANADA - September 18, 2008 - Biogen Idec (NASDAQ: BIIB) today announced that data was presented from the ASSURANCE (ASSessment of Drug Utilization, EaRly TreAtmeNt, and Clinical OutcomEs) study, showing the long-term benefits of AVONEX® (interferon beta-1a IM) therapy in patients with relapsing multiple sclerosis (MS) for up to 15 years. The ASSURANCE study represents the long-term follow-up of patients who participated in the Multiple Sclerosis Collaborative Research Group (MSCRG), the original Phase III pivotal trial from which AVONEX was approved. Data from this study were presented today as a poster presentation at the World Congress on Treatment and Research in Multiple Sclerosis in Montreal, Canada. This is the first joint meeting of the Americas Committee on Treatment and Research in Multiple Sclerosis (ACTRIMS) and its counterparts in Europe and Latin America: ECTRIMS and LACTRIMS.


MONTREAL, CANADA - September 18, 2008 - Biogen Idec (NASDAQ: BIIB) today announced that data was presented from the ASSURANCE (ASSessment of Drug Utilization, EaRly TreAtmeNt, and Clinical OutcomEs) study, showing the long-term benefits of AVONEX® (interferon beta-1a IM) therapy in patients with relapsing multiple sclerosis (MS) for up to 15 years. The ASSURANCE study represents the long-term follow-up of patients who participated in the Multiple Sclerosis Collaborative Research Group (MSCRG), the original Phase III pivotal trial from which AVONEX was approved. Data from this study were presented today as a poster presentation at the World Congress on Treatment and Research in Multiple Sclerosis in Montreal, Canada. This is the first joint meeting of the Americas Committee on Treatment and Research in Multiple Sclerosis (ACTRIMS) and its counterparts in Europe and Latin America: ECTRIMS and LACTRIMS.

"As a physician, my goal in treating my MS patients is to delay disability progression and help them maintain their normal lifestyle for as long as possible," said Robert Bermel, MD, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic. "This follow-up study identifies a group of patients who achieved benefits from long-term treatment, and underscores the importance of starting on and continuing an effective therapy for MS."

The data from the study show that patients currently taking AVONEX for up to 15 years (range of 3 - 15 years) versus those not on AVONEX therapy reported:

* Significantly lower disability progression as measured by a mean change in Expanded Disability Scale Scores (EDSS) of 2.3 vs. 3.3 (p=0.011) from MSCRG baseline;
* Lower disability progression to EDSS milestones four (64% vs. 83%, p=0.06), six (32% vs. 62%, p=0.008) and seven (9% vs. 33%, p=0.008);
* Greater quality of life as measured by the physical component score of the SF-36 (p<0.0001);
* Significantly greater sense of independence in self care (p=0.0019); and
* Significantly more independent living (p=0.031).

ASSURANCE was an open-label, retrospective, patient-reported, multicenter, 15-year follow-up study that included patients with relapsing MS who received ≤ 2 years of treatment in the pivotal Phase III trial (n=172). One hundred thirty-six of a possible 172 patients enrolled in the study. Patients were categorized as current AVONEX users and non-AVONEX users. Forty-six percent of those patients were currently taking AVONEX, with median treatment duration of 13.3 years. Patients not currently on AVONEX were treated with a number of other disease-modifying therapies, with 24 percent of patients undergoing treatment with TYSABRI® (natalizumab).

"This level of impact on disability and quality of life over the course of 15 years reinforces the real-life benefits and proven clinical effectiveness of AVONEX," said Thorsten Eickenhorst, MD, Vice President of Global Medical Affairs, Biogen Idec. "We pride ourselves on providing a treatment that is not only efficacious now but will continue to offer patients the support they need for as long as possible."
About AVONEX

AVONEX is the most prescribed treatment for relapsing forms of MS worldwide, with more than 130,000 patients on therapy. It was launched in the U.S. in 1996 and in Europe in 1997 for the treatment of relapsing forms of MS to slow the progression of disability and reduce relapses. AVONEX has been proven effective in clinical trials for up to three years. AVONEX is marketed internationally in more than 90 countries. AVONEX was the first treatment approved for patients who have their first clinical MS attack and have a brain MRI scan consistent with MS; this use was approved in Europe in 2002 and in the U.S. in 2003.

The most common side effects associated with AVONEX multiple sclerosis treatment are flu-like symptoms, including myalgia, fever, fatigue, headache, chills, nausea, vomiting, pain, and asthenia.

AVONEX should be used with caution in patients with depression or other mood disorders and in patients with seizure disorders. AVONEX should not be used by pregnant women. Patients with cardiac disease should be closely monitored. Patients should also be monitored for signs of hepatic injury. Routine periodic blood chemistry and hematology tests are recommended during treatment with AVONEX. Rare cases of anaphylaxis have been reported. For more information, visit www.AVONEX.com
About Biogen Idec

Biogen Idec creates new standards of care in therapeutic areas with high unmet medical needs. Founded in 1978, Biogen Idec is a global leader in the discovery, development, manufacturing, and commercialization of innovative therapies. Patients in more than 90 countries benefit from Biogen Idec's significant products that address diseases such as lymphoma, multiple sclerosis, and rheumatoid arthritis. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com.

For more information contact:

Media Contacts:

Shannon Altimari
617-914-6524

Investor Contacts:

Eric Hoffman
617-679-2812

Acorda Therapeutics Presents Additional Data from Second Positive Phase 3 Study of Fampridine-SR at World Congress on Treatment and Research in Multip





- Similar Response Rates Seen Across Different MS Subtypes and Background Therapies -

HAWTHORNE, N.Y.--(BUSINESS WIRE)--Sept. 20, 2008--Acorda Therapeutics, Inc. (NASDAQ: ACOR) today announced additional data from its second Phase 3 clinical trial of Fampridine-SR (MS-F204) on walking ability in people with multiple sclerosis (MS) at the late breaking news session of the World Congress on Treatment and Research in Multiple Sclerosis, being held in Montreal, Canada. Previously, the Company announced the trial met its primary endpoint with a significantly greater proportion of people taking Fampridine-SR having a consistent improvement in walking speed compared to people taking placebo (42.9% vs. 9.3%), as measured by the Timed 25-Foot Walk (p less than 0.001). The study also met its secondary outcome measure, leg strength, showing a statistically significant increase in the Fampridine-SR Timed Walk responders compared to placebo (p = 0.028).

New findings and information presented at the meeting from the study included:

-- The response rate for Fampridine-SR treated patients was
higher than placebo across all MS subtypes. Response rates for
the four major MS subtypes in the study were:
relapsing-remitting: 37.2%; secondary-progressive: 45.9%;
primary-progressive: 50.0%; and progressive-remitting: 40.0%.

-- Response rates were similar between study participants who
were being treated with immunomodulators and those who were
not.

-- The Fampridine-SR treated group showed improvement in the
Ashworth Score (a physician-reported measure of spasticity),
which was significant in an unplanned analysis.

-- Baseline demographic and disease characteristics of study
participants were also presented, including the percentage of
Fampridine-SR treated patients with each subtype of MS
(relapsing-remitting: 35.8%; primary-progressive: 8.3%;
secondary-progressive: 51.7%; and progressive-relapsing: 4.2%)
and the mean duration of disease in Fampridine-SR treatment
patients (14.43 years).

"People with MS often cite walking disability as one of the most challenging aspects of their disease, and there are no therapies currently indicated for improving walking in MS," said Andrew Goodman, M.D., Director of the Multiple Sclerosis Center at the University of Rochester, who presented the data. "The results of this study, which were consistent with the first Phase 3 Fampridine-SR trial, show that Fampridine-SR may provide benefit to people with walking difficulties."

Study Design

The double-blind, placebo-controlled trial was designed to evaluate the safety and efficacy of Fampridine-SR in improving walking ability in people with MS. The primary endpoint of the study was response on the Timed 25-Foot Walk. A Fampridine-SR Timed Walk responder was defined as a study participant whose walking speed was faster during at least three of the four on-drug visits than any speed measured during the five off-drug visits. This Timed Walk Response was validated for clinical meaningfulness in previous trials by showing that the response was associated with significant improvements in day-to-day disability, as measured by the 12-item MS Walking Scale (MSWS-12), and was also associated with significant improvements in both Subject and Clinician Global Impression scores. The trial, which enrolled 240 individuals at 39 MS centers in the United States and Canada, recruited patients between 18 and 70 years old with a definite diagnosis of MS and some degree of walking disability. Subjects were randomized to treatment with Fampridine-SR (n=120), at a dose of 10mg twice a day, or placebo (n=119), and the study was open to people with all four major types of MS: primary-progressive, secondary-progressive, relapsing-remitting and progressive-relapsing. Participants were permitted to remain on a stable regimen of their current medications, including immunomodulators.

Safety Statement

In this study, adverse events were generally mild to moderate and largely consistent with the safety profile observed in previous studies of Fampridine-SR in people with MS. The most common adverse events reported in the Fampridine-SR treatment group compared to the placebo group included: urinary tract infection (17.5% vs. 8.4%), falls (11.7% vs. 16.8%), insomnia (10.0% vs. 1.7%), headache (9.2% vs. 0.8%), asthenia (8.3% vs. 4.2%), dizziness (8.3% vs. 0.8%), nausea (8.3% vs. 0.8%), back pain (5.8% vs. 2.5%), balance disorder (5.8% vs. 1.7%), upper respiratory tract infection (5.8% vs. 6.7%), arthralgia (5.0% vs. 4.2%), nasopharyngitis (5.0% vs. 4.2%) and paraesthesia (5.0% vs. 1.7%).

There were three serious adverse events (SAEs) that led to discontinuation: two in the placebo group and one in the Fampridine-SR group. In the placebo group, one participant experienced a possible complex partial seizure and another experienced a combination of chest tightness and gastric reflux. Both of these events were judged by investigators, who were blinded at the time, to be possibly related to treatment. In the Fampridine-SR group, one participant had a patellar fracture, which was judged not to be treatment related. In addition, one participant treated with Fampridine-SR experienced an episode of syncope (fainting) one day after completing the treatment phase of the study. This was judged to be possibly related to treatment, but the participant was not discontinued from the trial. Follow-up assessment by the clinical investigators determined that these SAEs resolved completely with no residual effects. No deaths occurred during the study.

As of August 5, 2008, the total exposure in our MS studies to Fampridine-SR at 10mg twice a day, including both double-blind and open-label studies, is approximately 1,200 patient years. The incidence of seizures in these studies at the 10mg dose has been within the rates reported for placebo-treated groups in long-term controlled studies of immunomodulator drugs in MS patients. These rates have ranged up to two percent of patients in a two-year study, or one seizure per 100 patient years. The overall incidence of seizure appears to be dose-related.

About MS

Multiple sclerosis is a chronic, usually progressive disease in which the immune system attacks and degrades the function of nerve fibers in the brain and spinal cord. Over 400,000 Americans have MS, and someone is newly diagnosed with MS every hour in the United States. Most are between the ages of 20 and 50, and women are affected two to three times as much as men. Worldwide, MS may affect 2.5 million individuals.

According to the National Multiple Sclerosis Society (NMSS), the direct costs of medical care for MS patients in the United States exceed $6 billion annually. Additionally, a NMSS analysis estimated the total cost of MS, including medical and non-medical care, production losses, and informal care, at more than $47,000 per U.S. patient per year. Complications from MS may make it harder for people to work and may interfere with their ability to perform common daily activities.

For most people with MS, the disease slowly progresses with a series of unpredictable flare-ups, also called relapses. But for some, the progression of the disease is rapid. Each relapse tends to lead to increasing disabilities such as walking impairment, muscle weakness or speech or vision impairments. Research indicates 64% -85% of people with MS have difficulty walking, and 70% of people with MS who have difficulty walking report it to be the most challenging aspect of their MS. Within 15 years of an MS diagnosis, 50 percent of patients often require assistance walking and, in later stages, up to a third of patients are unable to walk.

About Fampridine-SR

Fampridine-SR is a sustained-release tablet formulation of the investigational drug fampridine (4-aminopyridine or 4-AP). In laboratory studies, fampridine has been found to improve impulse conduction in nerve fibers in which the insulating layer, called myelin, has been damaged. Fampridine-SR completed a second Phase 3 clinical trial to evaluate its safety and efficacy in improving walking ability in people with MS in June 2008.

Fampridine-SR and MS

A nerve cell has one extension, called an axon, which it uses to communicate via electrical signals to other nerve cells. All but the smallest axons have a special covering of a fatty substance called myelin that acts as insulation to preserve and speed these nerve signals, much like the insulating cover of an electrical cord helps preserve the transmission of electricity.

In MS, the myelin becomes damaged and the axon cannot effectively transmit electrical impulses. Specifically, the damaged myelin exposes channels in the membrane of the axon, which allow potassium ions to leak from the axon, dissipating the electrical current. In published studies, fampridine has been shown to block these exposed channels and help the electrical signals to pass through areas of damage.

About Acorda Therapeutics

Acorda Therapeutics is a biotechnology company developing therapies for spinal cord injury, multiple sclerosis and related nervous system disorders. The Company's marketed products include Zanaflex Capsules(R) (tizanidine hydrochloride), a short-acting drug for the management of spasticity. Acorda's lead clinical product, Fampridine-SR, recently completed a second Phase 3 clinical trial to evaluate its safety and efficacy in improving walking ability in people with MS. The Company's pipeline includes a number of products in development for the treatment, regeneration and repair of the spinal cord and brain.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, regarding management's expectations, beliefs, goals, plans or prospects should be considered forward-looking. These statements are subject to risks and uncertainties that could cause actual results to differ materially, including delays in obtaining or failure to obtain FDA approval of Fampridine-SR, the risk of unfavorable results from future studies of Fampridine-SR, Acorda Therapeutics' ability to successfully market and sell Fampridine-SR, if approved, and Zanaflex Capsules, competition, failure to protect its intellectual property or to defend against the intellectual property claims of others, the ability to obtain additional financing to support Acorda Therapeutics' operations, and unfavorable results from its preclinical programs. These and other risks are described in greater detail in Acorda Therapeutics' filings with the Securities and Exchange Commission. Acorda Therapeutics may not actually achieve the goals or plans described in its forward-looking statements, and investors should not place undue reliance on these statements. Acorda Therapeutics disclaims any intent or obligation to update any forward-looking statements as a result of developments occurring after the date of this press release.

CONTACT: Acorda Therapeutics
Jeff Macdonald, 914-347-4300 ext. 232
Cell: 917-371-0940
jmacdonald@acorda.com
or
Tierney Saccavino, 914-347-4300 ext. 104
Cell: 917-783-0251
tsaccavino@acorda.com

SOURCE: Acorda Therapeutics, Inc.

Opexa Announces Top-Line Results from Phase IIb Clinical Trial of Tovaxin® for the Treatment of Multiple Sclerosis




September 19, 2008 02:55 PM Eastern Daylight Time

Tovaxin Shows Favorable Annualized Relapse Rate and Excellent Safety Profile

MONTREAL--(BUSINESS WIRE)--Opexa Therapeutics, Inc. (NASDAQ:OPXA), a company dedicated to the development of patient-specific cellular therapies for the treatment of autoimmune diseases such as multiple sclerosis (MS) and diabetes, today announced top-line data from the company’s Phase IIb TERMS (Tovaxin® for Early Relapsing Multiple Sclerosis) study. Top-line results from the study demonstrated a positive trend in the reduction in annualized relapse rate (ARR) for patients treated with Tovaxin as compared to placebo. However, this finding did not achieve statistical significance. In addition, the study did not achieve statistical significance with its primary endpoint, the cumulative number of gadolinium-enhanced brain lesions.

Top-line results from the study showed that Tovaxin-treated patients experienced an ARR of 0.214 as compared to 0.339 for placebo-treated patients. Despite the low relapse rate in the placebo arm, this still represented a 37 percent decrease in ARR for Tovaxin as compared to placebo in the general population. Additionally, in the group of patients who had an ARR > 1 at study entry, Tovaxin demonstrated a 55 percent reduction in ARR as compared to placebo.

The study also demonstrated that Tovaxin was safe and well tolerated with no serious adverse events related to treatment. The most common adverse event related to Tovaxin was mild injection site reaction. Opexa believes that this favorable safety profile may be an important advantage as patient compliance represents a significant challenge due to serious side effects associated with many currently available MS treatments.

It is important to note that initial review of data revealed that patients in the study’s Tovaxin arm, on average had a substantially greater number of MRI brain lesions and corresponding lesion volumes at baseline compared to the average number of MRI brain lesions and lesion volumes per patient in the placebo group. The company believes that this unexpected imbalance may have contributed to the study not achieving its primary and secondary endpoints as patients in the Tovaxin arm began the study with greater disease burden and increased severity of disease.

“The annualized relapse rate of 0.214 seen in the Tovaxin treatment arm is on par with the lowest relapse rates observed with currently available MS treatments which range from 0.2 to 0.9. This rate is also consistent with ARRs that we have seen in the Tovaxin treatment arms in each of the three previously conducted Tovaxin clinical studies,” stated Neil K. Warma, president and chief executive officer of Opexa. “Findings further showed Tovaxin to possess an impressive safety profile with no serious adverse events related to treatment. This level of safety and tolerability addresses a critical unmet need for MS patients. We believe that these positive ARR results combined with an excellent safety profile and convenient dosing place Tovaxin in a very favorable position for continued development as an innovative MS therapy.”

Top-line data from the TERMS study were presented today by Edward J. Fox, M.D., Ph.D., director of the Multiple Sclerosis Clinic of Central Texas and the study’s principal investigator, at the World Congress on Treatment and Research in Multiple Sclerosis in Montreal, Canada.

“Multiple sclerosis is a disease that affects individual patients in distinctly different ways, highlighting the desire for a safe, effective and patient-specific therapy such as Tovaxin. With this in mind, we are pleased with the positive efficacy trend and excellent safety results witnessed in the TERMS study,” stated Dr. Fox. “The Tovaxin-induced reduction in ARR is particularly exciting as it suggests a reduction of clinical activity associated with MS. These study results are encouraging and supportive of further analysis of Tovaxin.”

About the TERMS Study

The TERMS study was a Phase IIb multi-center, randomized, double blind, placebo-controlled trial in 150 patients with Relapsing-Remitting Multiple Sclerosis or high risk Clinically Isolated Syndrome (CIS). The study involved 2:1 randomization with 100 patients receiving Tovaxin and 50 receiving placebo. According to the study protocol, patients received a total of five subcutaneous injections at weeks 0, 4, 8, 12 and 24. The primary efficacy endpoint of the TERMS trial was the cumulative number of gadolinium-enhanced brain lesions (CELs) using MRI scans summed over weeks 28, 36, 44 and 52. The trial’s secondary efficacy endpoints included annualized relapse rate (ARR), new CELs at weeks 28 through 52 and T2-weighted lesion volume compared to baseline.

Top-line data from the TERMS trial is as follows:

* ARR for Tovaxin-treated patients was 0.214 as compared to 0.339 for placebo-treated patients. Consistent with ARRs seen in previously conducted clinical trials for Tovaxin, this result is at the lower end of the spectrum of documented relapse rates demonstrated in controlled two-year clinical studies of currently marketed products (range from 0.2 to 0.9).

* For patients who had an ARR > 1 in the year prior to the study, Tovaxin demonstrated a 55 percent reduction in ARR as compared to placebo.

* Tovaxin was safe and well tolerated with no serious adverse events related to Tovaxin treatment. The most common adverse event was injection site irritation.

* Only 18 patients (12 percent) withdrew from the study prior to completion. The dropout percentage was identical for the Tovaxin and placebo arms of the study, providing further evidence of Tovaxin’s excellent safety and tolerability.

“We are especially pleased with the TERMS study’s ARR results, as this represents the most common efficacy endpoint evaluated by the FDA when approving MS therapeutics. Opexa expects that ARR will serve as the primary endpoint in any pivotal Phase III Tovaxin study,” commented Mr. Warma.

Opexa intends to complete a comprehensive analysis of all data from the TERMS study over the next several months. Based on the TERMS study results, Opexa expects to conduct a Phase II close-out meeting with the United States Food and Drug Administration during the first half of 2009. This meeting, along with the comprehensive results of the TERMS study, will provide important guidance as Opexa plans to advance Tovaxin into Phase III development.

Additionally, Opexa is conducting a one-year, open-label extension trial of the TERMS study called OLETERMS. Approximately 90 percent of patients in the TERMS study have elected to enroll in the OLETERMS trial.

Investigator Q&A Session

Opexa will host an investigator Q&A session following the conclusion of today’s programs at the World Congress on Treatment and Research in Multiple Sclerosis. A live webcast of the Q&A session will be available on Opexa’s web site at www.opexatherapeutics.com beginning at 6:00pm Eastern. The webcast will be archived until October 19, 2008.

Conference Call and Webcast

Opexa will host a conference call and webcast with company management to discuss the Phase IIb TERMS data and provide a corporate update on Monday, September 22, 2008, at 8:30 a.m. Eastern. The conference call can be accessed by dialing 800-230-1074 from the U.S. and 612-332-0228 internationally. Additionally a live webcast of the call will be available on Opexa’s web site at www.opexatherapeutics.com. The webcast will be archived until October 22, 2008.

A replay of the call can be accessed until September 29, 2008 at 11:59 p.m., by dialing 800-475-6701 from the U.S. and 320-365-3844 internationally, and entering the following access code: 960761.

About Tovaxin

Tovaxin is developed using Opexa’s proprietary method for the production of patient-specific T-cell vaccines. To produce the Tovaxin vaccine, Opexa isolates disease-causing T-cells from blood taken from an MS patient and expands them in the laboratory to create an appropriate therapeutic dose. The attenuated T-cells, which comprise the Tovaxin vaccine, are reintroduced into the patient via subcutaneous injection to trigger a therapeutic immune system response. Tovaxin is manufactured in Opexa’s in-house cGMP facility.

Opexa believes that Tovaxin may possess the following competitive advantages:

* Efficacy – Clinical trials conducted to date demonstrate that Tovaxin may result in a reduction in ARR (a key measure of MS treatment effectiveness) for patients with Clinically Isolated Syndrome (CIS), Relapsing-Remitting MS (RRMS) and Secondary-Progressive MS (SPMS) patients comparable to currently available MS therapeutics.
* Safety and Tolerability – Tovaxin treatment selectively targets and depletes the pathogenic T-cell population. It is not a general immune suppressant and accordingly, is not associated with the serious side effects seen with those MS treatments that function by systemically suppressing the immune system. In clinical trials conducted to date, including the 150-patient Phase IIb study, there have been no serious adverse events associated with Tovaxin treatment.

* Improved Compliance – In clinical trials, Tovaxin is administered only five times per year. This patient-friendly treatment regimen may provide significant compliance benefits compared to currently available MS treatments (at least once per month and, in some cases, as frequently as every day.

* Customized Therapy – Using the company’s proprietary Epitope Analysis Assay (EAA) to profile an individual’s disease profile, Opexa can continually customize treatments to specifically target an individual’s disease progression and/or modification.

About Opexa Therapeutics

Opexa Therapeutics is a biotechnology company dedicated to the development of patient-specific cellular therapies for the treatment of autoimmune diseases. The company’s leading therapies currently in development have the potential to address significant unmet medical needs in several large patient populations including multiple sclerosis (MS) and diabetes. The company's lead product is Tovaxin, a T-cell therapy for MS which recently completed a Phase IIb trial. The company also holds an exclusive worldwide license for adult multi-potent stem cells derived from mononuclear cells of peripheral blood. The technology provides means to differentiate these stem cells into other tissue types such as pancreatic islets. By using an individual’s own cells, this approach may minimize threat of treatment rejection. This technology serves as the basis for Opexa’s preclinical diabetes program, which is focused on the generation of insulin-secreting pancreatic-like cells. For more information visit the Opexa Therapeutics website at www.opexatherapeutics.com.

Cautionary Statement Relating to Forward - Looking Information for the Purpose of "Safe Harbor" Provisions of the Private Securities Litigation Reform Act of 1995

This press release contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements in this release do not constitute guarantees of future performance. Investors are cautioned that statements in this press release which are not strictly historical statements, including, without limitation, statements regarding current or future financial performance and position, management's strategy, plans and objectives for future operations, plans and objectives for product development, plans and objectives for present and future clinical trials and results of such trials, plans and objectives for regulatory approval, litigation, intellectual property, product development, manufacturing plans and performance, constitute forward-looking statements. Such forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those anticipated, including, without limitation, risks associated with: the success of collaborative relationships, our ability to compete with larger, better financed pharmaceutical and biotechnology companies, new approaches to the treatment of our targeted diseases, our expectation of incurring continued losses, our uncertainty of developing a marketable product, our ability to raise additional capital to continue our treatment development programs, the success of our clinical trials, our ability to develop and commercialize products, our ability to obtain required regulatory approvals, our compliance with all Food and Drug Administration regulations, our ability to obtain, maintain and protect intellectual property rights for our products, the risk of litigation regarding our intellectual property rights, our limited manufacturing capabilities, our dependence on third-party manufacturers and value added resellers, our ability to hire and retain skilled personnel, our volatile stock price, and other risks detailed in our filings with the Securities and Exchange Commission. We assume no obligation to update any forward-looking information contained in this press release or with respect to the announcements described herein.
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