Friday, June 20, 2008

Oral Agent Shows Promise Against Multiple Sclerosis





By Charles Bankhead, Staff Writer, MedPage Today
Published: June 19, 2008

MILAN, Italy, June 19 -- A new type of immumodulatory agent for relapsing-remitting multiple sclerosis led to a 40% reduction in lesions, according to results of a multicenter, placebo-controlled phase IIb trial.

Patients treated with laquinimod at a dose of 0.6 mg a day averaged 2.6 gadolinium-enhancing lesions on MRI compared with 4.2 for the placebo group (P=0.0048), Giancarlo Comi, M.D., of the University Vita-Salute here, and colleagues reported in the June 21 issue of The Lancet.

The between-group difference emerged early in the trial, and follow-up beyond the primary study period demonstrated even larger reductions in MRI-detected lesions with laquinimod versus placebo.

Additionally, the number of new lesions was reduced by 50% in the laquinimod group.

"The decrease of MRI activity during the last part of the study was evidence for both [gadolinium-enhancing] and new T2 lesions, indicating that laquinimod reduces not only the extent of blood-brain barrier opening, but also the accrual of fixed lesions," the authors said.

Available therapies for multiple sclerosis all target inflammatory aspects of the disease. In addition, all of the approved therapies require injection, creating a potential advantage for any oral agent.

Laquinimod is structurally related to linomide, a drug that reduced disease activity in MS but had unacceptable toxicity, the authors said. Preclinical and phase I clinical studies suggested laquinimod had greater activity and a more favorable safety profile compared with linomide.

In a previous 24-week, randomized phase II study, laquinimod 0.3 mg/d suppressed formation of new MS lesions and was well tolerated. Those results led to the current evaluation of two different doses of the drug.

The study involved 306 patients relapsing-remitting multiple sclerosis with who had had one or more relapses in the previous year and at least one gadolinium-enhancing lesion on screening MRI. Investigators at 51 centers in nine countries randomized the patients to placebo or to laquinimod 0.3 mg/d or 0.6 mg/d.

The trial lasted 36 weeks, and the primary outcome was the cumulative total of gadolinium-enhancing lesions from the final four MRI scans at weeks 24, 28, 32, and 36.

Compared with placebo, laquinimod 0.6 mg reduced the average number of lesions per scan on the final four MRI scans by 40.4%.

The 0.3 mg dose did not significantly reduce the number of lesions compared with placebo (3.9 versus 2.6).

Comparison of the median cumulative number of lesions from the last four MRI scans resulted in a 55% reduction in the number of lesions with laquinimod 0.6 mg versus placebo (4.0 versus 9.0).

The number of new T2 lesions on the last four scans was 44% lower with laquinimod 0.6 mg (P=0.0013), and the number of new T1-hypointense lesions was 51% lower in the laquinimod 0.6 mg group (P=0.0064).

Examination of MRI scans from weeks 12 through 36 demonstrated a 51% reduction in the mean number of gadolinium-enhancing lesions with laquinimod 0.6 mg (2.7 versus 4.4) and a 60% decrease in the median number of lesions (6.0 versus 15.0).

Patients in the laquinimod 0.6 mg group had an annualized relapse rate of 0.52 compared with 0.77 for those on placebo which was not statistically significant (P=0.0978). Additionally, 70.8% of laquinimod 0.6 mg patients were relapse-free compared with 62.7% of the placebo group.

Both doses of laquinimod were well tolerated, the authors said. The primary treatment-related effect was a transient, dose-related increase in liver enzymes.

In an accompanying commentary, B. Mark Keegan, M.D., and Brian G. Weinshenker, M.D., of the Mayo Clinic in Rochester, Minn., said the results raised several questions:

* Why was the 0.3 dose effective in the earlier phase II study but not in the current study?
* Was the limited duration the reason for the lack of difference in relapse rate?
* How does laquinimod's efficacy compare with that of other immunomodulatory agents?

They also noted that MRI gadolinium-enhanced lesions are not a perfect surrogate outcome: "The correlation between MRI ļ¬ndings and clinical disease course is, however, imperfect. Gadolinium-enhancing lesions are mildly predictive of relapse rate but not of clinical disability."

The Mayo clinicians also remained circumspect about the generally favorable safety profile of laquinimod.

"Continued vigilance is needed because serious adverse effects are commonly not in evidence until phase III studies are started . . . or until after approval," they said.

Teva Pharmaceutical Industries supported the study.

Dr. Comi reported consulting and speaking relationships with Teva, Novartis, sanofi-aventis, Merck-Serono, Biogen-Dompe, and Bayer Schering. Several coauthors also reported relationships with the pharmaceutical industry.

Dr. Weinshenker disclosed that he is a paid member of the data-safety monitoring committee for another oral agent being evaluated for multiple sclerosis.

Dr. Keegan declared that he has no conflicts.

Primary source: The Lancet

Source reference:
Comi G, et al "Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicenter, randomized, double-blind, placebo-controlled phase IIb study" Lancet 2008; 371: 2085-2092.

Additional source: The Lancet
Source reference:
Keegan BM, Weinshenker BG "Laquinimod, a new oral drug for multiple sclerosis" Lancet 2008; 371: 2059-2060.

Thursday, June 19, 2008

Peptimmune Initiates Phase Ib Study of PI-2301 in Multiple Sclerosis Patients and Presentation at BIO 2008

Peptimmune announces first patient dosed in a phase Ib study of PI-2301 in multiple sclerosis patients in one of the most comprehensive studies of the pharmacologic effects of an immunomodulatory compound in autoimmune disease.


CAMBRIDGE, Mass. – June 17, 2008. Peptimmune, Inc. a privately held biotechnology company, announced that physicians have treated the first participant in a clinical trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PI-2301 in subjects with Secondary Progressive Multiple Sclerosis (SP-MS). PI-2301 is a novel peptide copolymer for the treatment of multiple sclerosis and other autoimmune diseases.

The Phase Ib multiple-ascending dose, double-blind, placebo-controlled randomized study will involve up to fifty-three subjects with SP-MS who will receive the drug once weekly in four escalating-dose cohorts. Following establishment of safety at potentially therapeutic doses and proof of pharmacologic mechanism, the Company plans to initiate its Phase II study in multiple sclerosis patients in early 2009. "While the primary goal of this study is to demonstrate safety of PI-2301 in multiple sclerosis patients, we believe that this clinical trial is one of the most comprehensive looks at the pharmacologic effects of any immunomodulator in patients suffering from autoimmune diseases," stated Thomas P. Mathers, President and CEO of Peptimmune. Mr. Mathers will be presenting an overview of the PI-2301 clinical program at the BIO 2008 Business Forum, Wednesday, June 18th, at 9:00 a.m. PST at the San Diego Convention Center, Room 2.

PI-2301 is a second-generation peptide copolymer from a similar compound class as Copaxone® (Teva Pharmaceuticals). PI-2301 works through immune modulation by enhancing the regulatory response of the immune system and thereby controlling the pathogenic autoimmune response observed in some diseases. In a Phase I single ascending dose, double blind placebo controlled randomized study, all doses of PI-2301 were safe and well tolerated, and no serious adverse events were observed. Pharmacodynamic assays demonstrated evidence of immune exposure consistent with the pharmacologic mechanism of action for PI-2301, and dose-dependent pharmacokinetics was observed. PI-2301 has been optimized using Peptimmune’s novel platform peptide chemistry and, in preclinical studies, has shown to be more potent and effective than Copaxone in treating disease models for multiple sclerosis. PI-2301 has also shown efficacy in preclinical models of autoimmune diseases where immune modulation may be effective, such as Crohn’s disease, rheumatoid arthritis, and autoimmune uveitis. Peptimmune has put in place high-quality synthesis and analytical methods that provide a superior level of batch-to-batch reproducibility in the manufacturing of PI-2301.

Over 400,000 Americans have multiple sclerosis (MS), and MS may affect over 2.5 million individuals worldwide. MS is an autoimmune disease in which the individuals’ immune system responds against multiple components of nerve-insulating myelin. The effects of these immune-mediated attacks can range from relatively benign to somewhat disabling to devastating, as communication between the brain and other parts of the body is disrupted.


About Peptimmune

Peptimmune, Inc. is a privately held clinical stage biotechnology company focused on the development of peptide therapies to improve the management of chronic autoimmune and inflammatory disorders. The Company is in clinical development with second-generation therapeutics that are expected to result in safer and more effective products for multiple sclerosis and pemphigus vulgaris. Current investors include New Enterprise Associates, MPM Capital, Hunt Ventures, Boston Medical Investors, Silicon Valley Bank Capital, and Genzyme Corporation. For additional information, please contact us.

Tuesday, June 17, 2008

Accentia Reports on Multiple Sclerosis Study: Revimmune(R) Shows Unprecedented Results in Reducing Disability and Improving Functions




Accentia Biopharmaceuticals, Inc. (NASDAQ:ABPI) announced today that researchers from Johns Hopkins University have published encouraging results from a two-year study evaluating the treatment of aggressive relapsing-remitting multiple sclerosis with Revimmune(TM), Accentia's patent-pending, novel usage of an approved chemotherapeutic drug (cyclophosphamide) in an ultra-high dose, pulsed intravenous administration for four hours daily over four days. Administered in this fashion, cyclophosphamide acts as a unique stem-cell sparing myeloablative which can reboot the immune system in order to delete the autoimmunity. Furthermore, Revimmune is believed to be the first therapy in development for multiple sclerosis that proposes the restoration of neurological function with the potential to eliminate the autoimmunity.

The article titled "Reduction of Disease Activity and Disability with High-Dose Cyclophosphamide in Patients with Aggressive Multiple Sclerosis" was published in the Archives of Neurology. It concludes that Revimmune was safe and well-tolerated in patients, and that the therapy resulted in a pronounced reduction in disease activity and disability after treatment which was sustained during the course of follow-up for approximately two years. In contrast, existing approved therapies for the treatment of multiple sclerosis are only intended to slow progression of the disease, not improve the patient's functional status.

According to one of the study's authors, Dr. Douglas Kerr of Johns Hopkins University, "I believe our preliminary results in treating MS with Revimmune are unprecedented with an average functional score improvement of about 40% in these patients who were tracked for two years after receiving therapy with sustained restoration of their functional improvement. Of those nine patients, eight of them had failed other therapies, and during the course of follow-up, five of them had no signs of disease activity, and the other four showed dramatic improvement over the course of follow-up. We look forward to working closely with Accentia's team to advance Revimmune into a definitive phase 3 clinical trial, initially for refractory MS, but ultimately targeting a host of other autoimmune diseases as well."

A correspondent for the Reuters news organization, Will Dunham, reported on these findings in an article titled "New Approach Promising Against Multiple Sclerosis", which can be accessed at: http://www.reuters.com/article/latestCrisis/idUSN09228052

Revimmune therapy consists of an ultra-high intensity, short-course, intravenous formulation of cyclophosphamide. It is believed that Revimmune "reboots" a patient's immune system, thereby typically eliminating the autoimmunity. The "rebooting" process is achieved because Revimmune eliminates the cells causing the autoimmunity and spares the stem cells in the bone marrow. These surviving stem cells are then able to repopulate a restored, uncompromised immune system.

Accentia has filed a pre-IND submission with the FDA for the commencement of a Phase 3 trial, and the Company is preparing to file an IND later this year. Based on initial discussions with the FDA, the Company anticipates that the primary endpoint for this planned study will be the recovery of lost functions in multiple sclerosis patients.

About Accentia Biopharmaceuticals, Inc.

Accentia Biopharmaceuticals, Inc. (Nasdaq:ABPI) is committed to building significant value for its stockholders through the commercialization of patent-protected disruptive healthcare technologies designed to be positioned as leading products for the treatment of a broad range of chronic, debilitating and life-threatening diseases including respiratory, autoimmune and cancer indications. The Company generated more than $18 million in revenues in fiscal-year 2007, primarily based on sales of its marketed specialty pharmaceutical products and its analytical consulting business serving biopharmaceutical clients.

Accentia is advancing a portfolio of potential blockbuster drug candidates which target multi-billion dollar market opportunities. These late-stage products include: BiovaxID(R), a novel anti-idiotype cancer vaccine for the treatment of B-cell malignancies including indolent follicular non-Hodgkin's lymphoma; Revimmune(TM), a novel ultra-high-dose formulation of a previously approved chemotherapeutic agent expected to show utility in the treatment of up to 80 autoimmune diseases, with an initial focus on multiple sclerosis; and SinuNase(TM), a novel formulation of a previously approved anti-fungal for the topical, intranasal treatment of chronic sinusitis.

Accentia's interest in BiovaxID is based on its majority ownership stake in Biovest International, Inc. (OTCBB:BVTI), and Accentia also maintains a royalty interest in Biovest's biologic products. Accentia is a portfolio company of the Hopkins Capital Group.

For further information, please visit: http://www.Accentia.net

Forward-Looking Statements:

Statements in this release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, statements about Revimmune(TM), SinuNase(TM), BiovaxID(R), AutovaxID(TM), SinuTest(TM), AllerNase(TM) and any other statements relating to products, product candidates, product development programs, the FDA or clinical study process including the commencement, process, or completion of clinical trials or the regulatory process. Such statements may include, without limitation, statements with respect to the Company's plans, objectives, expectations and intentions, and other statements identified by words such as "may," "could," "would," "should," "believes," "expects," "anticipates," "estimates," "intends," "plans," or similar expressions. Such forward-looking statements involve known and unknown risks, uncertainties, and other factors that may cause the actual results of Accentia to be materially different from historical results or from any results expressed or implied by such forward-looking statements. These factors include, but are not limited to, risks and uncertainties related to the progress, timing, cost, and results of clinical trials and product development programs; difficulties or delays in obtaining regulatory approval for product candidates; competition from other pharmaceutical or biotechnology companies; and the additional risks discussed in filings with the Securities and Exchange Commission. All forward-looking statements are qualified in their entirety by this cautionary statement, and Accentia undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. The product names used in this statement are for identification purposes only. All trademarks and registered trademarks are the property of their respective owners.

Saturday, June 14, 2008

Opexa Therapeutics Reports Favorable Two-Year Data in Phase I/II Retreatment Studies of Tovaxin® for Multiple Sclerosis





73% of patients remained relapse-free at two years

THE WOODLANDS, Texas--(BUSINESS WIRE)--Opexa Therapeutics, Inc. (NASDAQ:OPXA), a cell therapy development and commercialization company, today announced favorable safety and efficacy data for Tovaxin®, the Company’s investigational T-cell vaccination therapy for multiple sclerosis (MS), in the second year of open-label clinical retreatment studies in patients with MS.

The “intent to treat” population of 22 patients included 13 with relapsing remitting multiple sclerosis (RRMS) and nine with secondary progressive multiple sclerosis (SPMS). An analysis of disease progression of disability over a two year period, as measured by a 1.0 or greater change in Expanded Disability Scoring Scale (EDSS), showed that 27.3% of patients demonstrated sustained improvement, 59.1% had no disease progression and 13.6% experienced sustained worsening of disability. The improvement in the EDSS scores ranged from 1.0 to 4.5 (average 2.41). During the two-year study period 72.7% of patients remained relapse-free.

Brian Loftus, M.D., of Bellaire Neurology and the principal investigator of the studies, commented, “I’m pleased to see that subjects in the study experienced sustained positive clinical outcomes over the two-year period. It was especially encouraging to see a lack of disease progression in more than 86% of the patients after two years, given the later stage of disease of this subject population.”

The annualized relapse rate analysis of 17 patients (which excludes five patients with no prior relapses in their two-year pre-study baseline) showed Tovaxin therapy achieved an 82% reduction in annualized relapse rate (ARR) in patients over a two-year period (p<0.0001) to 0.21 relapses per year, compared with 1.38 relapses per year in the patients’ prior two-year baseline. For RRMS patients (n=12) the ARR over a two-year period was 0.26 relapses per year, compared with 1.63 relapses per year in the patients’ prior two-year baseline; for SPMS patients (n=5) the ARR over a two-year period was 0.10 relapses per year, compared with 0.80 relapses per year in the patients’ prior two-year baseline.

“Approximately three out of four patients re-treated in the second year exhibited a change in their myelin-reactive T-cell profile, which was the basis for producing their individualized T cell vaccine,” said David McWilliams, president and chief executive officer of Opexa. “We believe this new data supports the continuation of our development strategy of individually monitoring patients with our proprietary epitope analysis assay and re-treating them with a patient-specific therapeutic vaccine that associates with their clinical status.”

The combined analysis included patients participating in second-year extension protocols from the Phase I/II dose-escalation study and the Phase I/II re-treatment study, and 19 of 22 patients were re-treated with Tovaxin during the study period. Patients did not receive any other disease modifying therapies during the two-year study period.

Tovaxin was well-tolerated throughout the two-year study period. The safety profile revealed only mild-to-moderate injection site reactions and no serious adverse reactions related to T-cell vaccination.

About Multiple Sclerosis

In the U.S. approximately 400,000 people suffer from MS, a chronic progressive autoimmune disease of the central nervous system that is caused by myelin autoreactive T-cells progressively eroding the myelin that surrounds and insulates nerve fibers of the brain and spinal cord resulting in varying amounts of disability. Globally, there are approximately 2.5 million MS patients representing a drug therapy market believed to be approximately $5 billion in 2005. The US markets accounted for slightly more than half of global MS sales in 2005.

MS remains a challenging autoimmune disease to treat because the pathophysiologic mechanisms are diverse, and the chronic, unpredictable course of the disease makes it difficult to determine whether the favorable effects of short-term treatment will be sustained. Therapies that are easy to use and can safely prevent or stop the progression of disease represent the greatest unmet need in MS. The most common phase of MS at the time of diagnosis is relapsing-remitting, which affects approximately 70% of MS patients. This group experiences clearly defined flare-ups (relapses), followed by partial or complete remissions between attacks that are free of disease progression. Approximately 50% of the relapsing-remitting patients develop the secondary-progressive form of the disease within 10 years of diagnosis. This phase is characterized by an initial period of relapsing-remitting disease followed by steady worsening with or without flares or minor remissions.

About Tovaxin for Multiple Sclerosis

Tovaxin is an individualized T-cell therapeutic vaccine that consists of attenuated patient-specific myelin-reactive T-cells (MRTCs) against peptides of proteins from Myelin basic protein (MBP), Myelin oligodendrocyte glycoprotein (MOG) and Proteolipid protein (PLP) or combinations thereof. Patient-specific MRTCs are expanded in culture with specific peptides identified by assaying peripheral blood mononuclear cell reactivity against peptides derived from the three myelin proteins. Studies have shown that T-cell vaccination resulted in the in vivo induction of CD8+ cytotoxic T-cells and CD4+CD25+FoxP3 Tregs specific for T-cell vaccine. The induction of anti-idiotypic cytotoxic CD8+ effector T-cells and anti-ergotypic CD4+CD25+FoxP3 positive Tregs is believed to provide a therapeutically effective dual mechanism of protection to patients treated with Tovaxin. The observed regulatory immune responses have been shown to collectively relate with clinical improvement in treated patients. Tovaxin has been previously studied in two Phase I/II open-label trials. A 150-patient Phase IIb one-year double blind placebo controlled study to evaluate the efficacy, safety and tolerability of Tovaxin in subjects with clinically isolated syndrome (CIS) or relapse-remitting multiple sclerosis (RR-MS) is nearing completion.

About Opexa Therapeutics

Opexa Therapeutics develops and commercializes cell therapies to treat autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and diabetes. The Company is focused on autologous cellular therapy applications of its proprietary T-cell and stem cell therapies. The Company's lead product is Tovaxin, a T-cell therapy for multiple sclerosis is in Phase IIb trials. The Company holds the exclusive worldwide license for adult multipotent stem cells derived from mononuclear cells of peripheral blood. The technology allows large quantities of monocyte-derived stem cells to be produced efficiently for use in autologous therapy, thus circumventing the threat of rejection. The Company is in preclinical development for diabetes mellitus. 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," including statements about Opexa Therapeutics' growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. These forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Opexa Therapeutics' ability to obtain additional funding, develop its stem cell technologies, obtain FDA approval for its therapeutic products, achieve its operational objectives, and obtain patent protection for its discoveries, that may cause Opexa Therapeutics' actual results to be materially different from any future results expressed or implied by such forward-looking statements. Opexa Therapeutics undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

High-Dose Cyclophosphamide Reduces Disability in Aggressive Multiple Sclerosis





June 12, 2008 — High-dose cyclophosphamide (HiCy) reduces disease activity and disability in people with severe aggressive multiple sclerosis (MS) who have not undergone bone marrow transplantation.

In a 2-year open-label trial of 9 patients with aggressive relapsing remitting MS (RRMS), investigators at Johns Hopkins University in Baltimore, Maryland, found that administering a 1-time immunoablative regimen of 50 mg per kilogram of intravenous cyclophosphamide over 4 consecutive days resulted in a statistically significant reduction in disability that was durable at an average follow-up of 23 months, with no adjunctive immunomodulatory therapies.

"We did not expect this [reduction in disability]. We found that disability levels at the beginning of the study were much greater than at the end of the study. Patients had a return of function that, for some, translated into significant improvements, such as returning to work, dispensing with walkers or canes, and regaining bladder control," Douglas A. Kerr, MD, PhD, told Medscape Neurology & Neurosurgery.

Furthermore, the treatment appeared safe and well tolerated, with no deaths or unexpected serious adverse events.

The study was published online June 9 in the Archives of Neurology.

Starting From Scratch

Cyclophosphamide, a chemotherapeutic agent, has been used for about half a century, primarily to treat cancer. When it was used to treat MS in the 1980s, its efficacy as a single-pulse therapy was, at best, modest and did not justify its routine use, said Dr. Kerr.

Currently, cyclophosphamide is often used as a component of a chemotherapeutic cocktail given as adjunctive therapy preceding bone marrow transplantation for the treatment of RRMS.

The HiCy 1-time regimen used in the current study has been shown to be safe and effective in other autoimmune diseases, including lupus erythematosus, autoimmune aplastic anemia, and myasthenia gravis.

The regimen, which was developed about 15 years ago by Robert Brodsky, MD, and Richard Jones, MD, hematologists at Johns Hopkins, works by eliminating the "misbehaving" immune system while preserving hematopoietic stem cells, allowing the immune system to "recreate itself from scratch." Based on promising results and these other autoimmune conditions, the investigators decided to test it in MS.

Worst of the Worst

Nine patients — 6 men and 3 women — with RRMS were selected for the study. The mean age of the participants was 29 years. Eight subjects had failed conventional therapy and 1 was treatment naive. All had ongoing active inflammatory disease and a high risk for continued progression and loss of function.

"These patients were the worst of the worst in terms of the severity of their disease," said Dr. Kerr.

The primary end point was safety and tolerability of the treatment. Secondary outcome measures included a change in gadolinium-enhancing lesions on magnetic resonance imaging and a change in disability measures on the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC).

At a mean follow-up of 23 months, investigators found an average reduction of 39.4% in disability and an average improvement in MSFC scores of 87%. In addition, the average number of brain lesions decreased, from 6.5 at study outset to 1.2 at follow-up.

Of the 9 study subjects, 5 had no disease activity at follow-up. The other 4, said Dr. Kerr, "did well, but not perfectly, and had some evidence of disease activity, usually demonstrated by a brain lesion and not a clinical attack. Still, it wasn't perfect."

Nevertheless, he said, overall patients experienced a dramatic improvement with this 1-time high-dose therapy that appears to reverse MS-related disability and is unlike any previous MS treatment.

Currently, he said, MS drugs that are available, or even those that are on the horizon, are designed solely to hold the disease at bay and limit disease progression. However, once patients stop taking the medication, the disease continues to advance.

"This treatment is based on a completely different model — a 1-time therapy with a long-term benefit," said Dr. Kerr.

Less Toxicity, Lower Cost

HiCy also offers several advantages over bone marrow transplantation, which has been associated with a 5% to 7% mortality rate and toxicity to a number of organs, including the brain. To date, he said, there has been no mortality or organ toxicity associated with HiCy therapy in the more than 250 patients who have received the treatment for other types of autoimmune disease.

Furthermore, the cost of bone marrow transplantation runs about $300,000 in the first year alone; HiCy therapy costs approximately $25,000 to $30,000.

Although the mechanism is not entirely clear, Dr. Kerr said it was interesting to note that patients with a return of function tended to have a shorter disease duration (less than 10 years) and more active inflammatory disease.

This finding is important, he said, and suggests that inflammation itself plays a role in MS disability and that "once you get rid of that inflammatory cascade within the nervous system, patients start to improve."

Dr. Kerr said his team is currently working on improving the HiCy regimen, possibly by adding drugs that will help "reeducate" the immune system. In addition, he said, the investigators are also planning a multicenter phase 3 trial that will have broader inclusion criteria, enrolling patients with less severe, less aggressive disease.

The study was supported by General Clinical Research Center of the Johns Hopkins School of Medicine, the National Multiple Sclerosis Society, Mr. Alvin Myerberg, and the Johns Hopkins Project RESTORE.

Arch Neuro. Published online before print June 9, 2008.


Caroline Cassels is a Senior Journalist for Medscape Neurology & Neurosurgery. A medical and health journalist for 20 years, Caroline has written extensively for both physician and consumer audiences. She helped launch and was the editor of Health Digest, an award-winning Canadian consumer health publication. She was also national editor of the Heart & Stroke Foundation of Canada's Web site before joining Medscape Neurology & Neurosurgery in 2005. She is the recipient of the 2008 American Academy of Neurology Journalism Fellowship Award. She can be contacted at CCassels@medscape.net.

Medscape Medical News 2008. © 2008 Medscape


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Monday, June 09, 2008

New Data on Disease-modifying Therapies for Multiple Sclerosis





Mark J. Tullman, MD

Introduction

New data from key clinical trials of disease-modifying therapy were presented at the 60th Annual Meeting of the American Academy of Neurology. The results of some of these studies, along with the potential clinical implications of those results, are presented below.

Efficacy of Interferon Beta-1b and Glatiramer Acetate in Patients With Relapsing-Remitting Multiple Sclerosis: The BEYOND Trial

Results of the Betaferon/Betaseron Efficacy Yielding Outcomes of a New Dose (BEYOND) trial, which was funded by Bayer Healthcare Pharmaceuticals, were presented in a late-breaking session by Paul O'Connor, MD.[1] This trial was designed to compare the efficacy of 250 micrograms (mcg) and 500 mcg of interferon beta-1b given subcutaneously (SC) every other day in patients with relapsing-remitting multiple sclerosis (RRMS). The efficacy of these two doses of beta interferon-1b was also compared with glatiramer acetate (20 mg SC administered daily).

The trial randomized treatment-naive patients with RRMS with Expanded Disability Status Scale (EDSS) scores equal to or less than 5. Patients also had to have at least one relapse in the year prior to entry into the study. A total of 2244 patients were randomized in a 2:2:1 ratio to the 500-mcg dose of beta interferon-1b (n = 899), the 250-mcg dose of interferon beta-1b (n = 899) or to the 20-mg dose of glatiramer acetate (n = 448) for a period of 104 weeks or longer. Patients underwent clinical evaluations every 3 months and brain magnetic resonance imaging (MRI) scans annually.

The trial's primary endpoint was relapse risk. A per-protocol analysis and an intent-to-treat analysis were performed on the data. The clinical efficacy of each of the 3 treatment groups (beta interferon-1b 250 mcg, beta interferon-1b 500 mcg, and glatiramer acetate 20 mg) was similar in each of the analyses.

There were several supportive endpoints, including relapse rate, proportion of relapse-free patients, and time to first relapse. Secondary outcome variables were time to confirmed EDSS progression and T1 black hole development. Other endpoints of interest included the number and volume of T2 lesions. The annualized relapse rate fell by nearly 80% compared with the year prior to enrollment in the study, but there were no significant differences among the treatment groups.

There were some MRI endpoints that showed statistically significant differences between the treatment groups. The cumulative number of T2 lesions up to the last scan was significantly higher in the group receiving glatiramer acetate compared with the groups receiving 250 mcg (P = .17) or 500 mcg (P = .001) beta interferon-1b. Additionally, patients receiving 250 mcg or 500 mcg beta interferon-1b had a significantly lower increase in T2-lesion volume compared with the group receiving glatiramer acetate (P < .001 and P = .001, respectively). The authors note that it is unclear whether there is any long-term clinical significance to these findings.

All 3 treatments were generally well-tolerated. Dropout rates for 250 mcg interferon beta-1b, 500 mcg interferon beta-1b, and glatiramer acetate were 13%, 19%, and 17%, respectively. It is important to note that although this was a double-blind study for the interferon beta-1b groups (ie, they were unaware which dose they were receiving), this was not a double-blind trial for the patients who received glatiramer acetate. This may explain the higher dropout rate in the group receiving glatiramer acetate (17%) compared with the group receiving 250 mcg interferon beta-1b (13%) because the patients receiving interferon beta-1b were aware that there was a 50% chance that they could be receiving the higher, and potentially more effective, dose of interferon beta-1b.

The adverse events observed were similar to the known adverse event profiles of these compounds. Flulike symptoms were more common with interferon beta-1b and injection-site reactions (eg, pain, pruritis) were more common with glatiramer acetate.

The Results of the BEYOND trial[1] are similar to the recently presented results from the REGARD trial[2] that compared interferon beta-1a 44 mcg SC 3 times a week to glatiramer acetate. In these 2 studies, more than 2000 patients were randomized to either high-dose interferon or glatiramer acetate. Patients did very well and there were no major differences in terms of efficacy between the therapies. Unfortunately, the 500-mcg dose of interferon beta-1b was no more effective than the 250-mcg dose. In the absence of clear superior efficacy data between the high-dose interferons and glatiramer acetate, it seems to me that a high-dose interferon and glatiramer acetate are both reasonable initial treatment options for most patients with RRMS. Patients should be well informed and part of the treatment decision process. Some patients may prefer starting with a daily injection with fewer side effects and others would rather take a medication that has fewer injections but the potential to cause more side effects and requires periodic blood work.

Furthermore, for patients on a high dose interferon of glatiramer acetate who experience persistent side effects, switching from one agent to the other might improve tolerability and enhance quality of life without sacrificing efficacy.

Efficacy of Glatiramer Acetate in Delaying Conversion to Clinically Definite Multiple Sclerosis: The PreCISe Trial

Results from the Study to Evaluate the Effect of Early Glatiramer Acetate Treatment in Delaying the Conversion to CDMS of Subjects Presenting With a Clinically Isolated Syndrome (CIS) (PreCISe) trial, were presented in a late-breaking session by Giancarlo Comi.[3] The PreCISe trial was a randomized, double-blind, placebo-controlled, multicenter, 3-year study designed to evaluate the efficacy of early treatment with glatiramer acetate in delaying the progression to clinically definite MS (CDMS) in patients with clinically isolated syndromes (CIS), which are considered to be first events suggestive of MS.

The study randomized 481 patients who had a minimum of 2 T2-weighted brain lesions at least 6 mm in diameter shown on MRI and who had experienced a first clinical event to receive glatiramer acetate 20 mg/day SC (n = 243) or placebo (n = 238). Only patients with a unifocal disease manifestation were included. Key baseline characteristics were: age (31.1 ± 6.9 years), time from first event to randomization (74.0 ± 14.9 days), and corticosteroid use for first attack (64% of patients). There was no difference between the study arms in EDSS (1.0 ± 1.0), number (31.5 ± 30.7) and volume (6.0 ± 6.2ml) of T2 weighted lesions, and number (1.5±2.9) and volume (0.3 ± 0.6ml) of gadolinium enhanced lesions.

The primary endpoint of the study was time to CDMS based on a second clinical attack. The trial was stopped prematurely by the data and safety monitoring committee after a preplanned interim analysis. The group initially receiving placebo was then switched to active treatment on an open-label basis. At this point, about 80% of the planned drug exposure had been given, and CDMS had developed in about 43% of those patients in the placebo group compared with just 25% in the glatiramer acetate group. The odds ratio for progression to CDMS was 0.41 (P < .0001) and the hazard ratio for progression to CDMS was 0.55 (95% CI 0.40-0.77; P = .0005) in the group taking glatiramer acetate compared with the placebo group. This translates in to a 45% risk reduction for progression to CDMS in the group on active treatment compared with the group on placebo. Additionally, the 25th percentile time to CDMS was prolonged from 336 days in the placebo group to 722 days (115% increase in time to CDMS onset) in the group receiving glatiramer acetate.

The results of MRI scans also favored the group receiving glatiramer acetate compared with the group receiving placebo. The mean number of new T2-weighted lesions was reduced by 61% in the patients receiving glatiramer acetate compared with the patients receiving placebo (P < .0001). Similarly, patients receiving glatiramer had a 61% reduction in new T1 gadolinium-enhancing lesions compared with the group receiving placebo (P < .0001).

Glatiramer acetate was well tolerated, and side effects were similar to those previously reported in patients with CDMS, including local injection-site reactions and transient postinjection reactions including chest pain, flushing, dyspnea, palpitations, and anxiety.

The open-label extension phase of the study will continue to a 5-year follow-up to evaluate the potential for glatiramer acetate to prevent or delay clinical progression of the disease. Patients will receive glatiramer acetate and will be followed until the development of CDMS.

The PreCISe study results are really not surprising. However, we now have strong evidence that the interferons and glatiramer acetate are effective when initiated after a first MS attack in patients with at least minimally abnormal brain MRI. The 5-year PreCISe data may provide additional evidence that early treatment with MS immunomodulatory therapy prevents the development of disability.

This activity is supported by an independent educational grant from Teva Neuroscience.

Wednesday, June 04, 2008

Acorda Therapeutics Announces Positive Data from Second Phase 3 Study of Fampridine-SR on Walking Ability in People with Multiple Sclerosis





Company Plans to File New Drug Application (NDA) in First Quarter of 2009

Investor Conference Call and Webcast Today at 8:30 A.M. ET
HAWTHORNE, N.Y.--(BUSINESS WIRE)--June 2, 2008--Acorda Therapeutics, Inc. (NASDAQ: ACOR) today announced positive results from its second Phase 3 clinical trial of Fampridine-SR (MS-F204) on walking ability in people with multiple sclerosis (MS). A significantly greater proportion of people taking Fampridine-SR in the trial had 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). Consistent improvement in walking speed was the primary endpoint of the study as outlined in the Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA).

"With the success of this trial, we have achieved a critical milestone for Fampridine-SR. We have now completed two successful Phase 3 trials demonstrating improved walking ability in people with MS," said Ron Cohen, M.D., President and CEO of Acorda Therapeutics. "We believe that, subject to FDA review, the results of our two Phase 3 trials are adequate to support an NDA. We expect to submit this application in the first quarter of 2009 and plan to request priority review."

The study's only prospectively defined secondary outcome measure, leg strength, showed a statistically significant increase in the Fampridine-SR Timed Walk responders compared to placebo (p = 0.028). There was a small improvement in leg strength for Fampridine-SR Timed Walk non-responders compared to placebo that was not statistically significant.

Additional measures in this study were consistent with the results of the first Phase 3 Fampridine-SR trial. The average increase in walking speed over eight weeks of treatment compared to baseline was 24.7 percent for the Fampridine-SR Timed Walk responders compared to 7.7 percent for the placebo group. The 12-Item Walking Scale (MSWS-12), a self-rated assessment of walking disability, was improved in Timed Walk responders compared to non-responders. Also, an increased response rate on the Timed 25-Foot Walk was seen across all four types of MS. The Company intends to present comprehensive data from this trial at an upcoming medical meeting.

"Difficulties with walking are among the most pervasive and debilitating problems faced by people with MS. Walking disability affects their ability to accomplish daily tasks and limits their independence," said Andrew Goodman, M.D., Director of the Multiple Sclerosis Center at the University of Rochester. "Because there are currently no therapies indicated to improve walking impairment in MS, clinicians are limited in their ability to address this aspect of the disease. The results of this study indicate that Fampridine-SR could represent an important new way to treat people with MS."

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 at a majority of the four on-drug visits than any speed measured during the five off-drug visits. 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 June 2, 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 1,100 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. Approximately 85 percent of people with MS experience some form of walking impairment. 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 is being developed by Acorda Therapeutics and manufactured by Elan Corporation plc.

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.

Conference Call and Audio Webcast

Acorda will hold a conference call and audio webcast today at 8:30 a.m. ET to discuss the top-line results from the trial. To access the call, please dial 866-578-5801(domestic) or 617-213-8058 (international) and provide the access code 57594133. To access the audio webcast, please go to the Investor Relations "Calendar of Events" section of the Acorda website at www.acorda.com, or you may use the link: http://phx.corporate-ir.net/phoenix.zhtml?p=irol-eventDetails&c=194451&eventID=1866966 . (Due to its length, this URL may need to be copied/pasted into your Internet browser's address field. Remove the extra space if one exists.)

A replay of the call will be available from 10:30 a.m. ET on June 2, 2008 until 11:59 p.m. ET on July 2, 2008. To access the replay, please dial 888-286-8010 (domestic) or 617-801-6888 (international), and provide the access code 37448849. An archived version of the webcast will be available for 90 days on the Acorda website in the Investor Relations section.

Patient Information Line

Patients with questions regarding the results of this study or who want to join Acorda's mailing list to be kept informed of future company news may call 877-617-2494, toll-free, weekdays from 10:00 a.m. to 5:00 p.m. ET.

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, has completed two Phase 3 clinical trials to evaluate its safety and efficacy to improve 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 nervous system.

About Elan Drug Technologies

Elan's Drug Technologies group has developed Fampridine-SR tablets using one of its proprietary Oral Controlled Release Technologies, the MXDAS(TM) (MatriX Drug Absorption System) Technology. Elan Drug Technologies (EDT) is an established, profitable and growing specialty pharmaceutical business unit of Elan Corporation plc. For nearly 40 years, EDT has been applying its skills and knowledge to enhance the performance of dozens of drugs that have been marketed worldwide. EDT is focused on using its extensive experience, proprietary drug delivery technologies and licensing capabilities to develop innovative products that deliver clinically meaningful benefits to patients. More information about EDT's broad range of technologies including their Oral Controlled Release and NanoCrystal(R) Technology Platforms, their patent estate and range of services is available at www.elan.com/EDT.

Acorda Therapeutics, Inc. Forward-Looking Statements

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 Zanaflex Capsules(R), 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
Media:
Jeff Macdonald, 914-347-4300 ext. 232
jmacdonald@acorda.com
or
Investor Relations:
Molly Newton, 914-347-4300 ext. 203
mnewton@acorda.com

SOURCE: Acorda Therapeutics, Inc.

BIOMS MEDICAL’S RELAPSING-REMITTING MULTIPLE SCLEROSIS TRIAL RECEIVES POSITIVE REVIEW FROM DATA SAFETY MONITORING BOARD





Edmonton, Alberta, May 27, 2008 – BioMS Medical Corp. (TSX: MS), a leading developer in the treatment of multiple sclerosis (MS), today announced that the independent Data Safety Monitoring Board (DSMB) for the Company's phase II MINDSET-01 trial of MBP8298 (dirucotide) in patients with relapsing-remitting MS has completed a safety analysis and recommended that the trial continue as per the protocol.

This was the fourth of several regularly scheduled reviews by the DSMB that will occur over the duration of the trial. The purpose of the DSMB is to provide objective, independent safety monitoring of the trial.

MINDSET-01 Trial
The MINDSET-01 phase II, double-blind, placebo-controlled trial is designed to evaluate the safety and efficacy of MBP8298 (dirucotide) in patients with relapsing-remitting MS. The fifteen month trial is fully enrolled with 218 patients at 24 sites in 6 countries. The objectives of the study are to demonstrate safety and efficacy of MBP8298 (dirucotide) versus placebo as measured by relapse rate, MRI activity and disease progression.


About BioMS Medical Corp.
BioMS Medical is a biotechnology company engaged in the development and commercialization of novel therapeutic technologies. BioMS Medical’s lead technology, MBP8298 (dirucotide), is for the treatment of multiple sclerosis and is being evaluated in two pivotal phase III clinical trials for secondary progressive MS patients, MAESTRO-01 in Canada and Europe and MAESTRO-03 in the United States. It additionally is being evaluated for relapsing remitting MS patients in a Phase II trial in Europe entitled MINDSET-01. In December 2007, BioMS entered into a licensing and development agreement granting Eli Lilly and Company exclusive worldwide rights to MBP8298 (dirucotide) in exchange for an $87 million upfront payment, milestone payments and escalating royalties on sales. For further information please visit our website at www.biomsmedical.com.



Ryan Giese
VP Corporate Communications
Phone: 780-413-7152
rgiese@biomsmedical.com Tony Hesby

Executive VP Corporate Affairs
Phone: 780-413-7152
tony.hesby@biomsmedical.com

Amanda Stadel
Investor Relations Manager
Phone: 780-413-7152
astadel@biomsmedical.com

Extavia® approved in European Union for treatment of multiple sclerosis, first in planned portfolio of therapies from Novartis





Extavia is Novartis brand for interferon beta-1b - an established therapy with more than 700,000 patient-years' experience to date[1]

Launch of Extavia for early and relapsing forms of multiple sclerosis (MS) planned for US and Europe in first half of 2009
Novartis committed to MS through extensive research and development programs, including novel oral therapy FTY720 currently in Phase III trials

MS, a devastating disease causing progressive disability, affects an estimated 2.5 million people worldwide, including many young adults[2]

Basel, May 26, 2008 - The European Commission has approved Extavia® (interferon beta-1b) for the treatment of early and relapsing forms of multiple sclerosis (MS) - the first in a new portfolio of medicines from Novartis that is planned to include both established treatments and innovative therapies for patients with MS.

Extavia is the Novartis branded version of interferon beta-1b, a first-line disease-modifying therapy injected every other day for the treatment of MS. Interferon beta-1b has been available globally for more than 13 years and is supported by more than 700,000 patient-years of experience[1].

Formerly known as NVF233, Extavia is the same medicine as Betaferon®/Betaseron®, which is marketed by Bayer-Schering and was the first beta interferon treatment for MS. Novartis gained rights to its own branded version of this medicine in agreements with Bayer-Schering related to the acquisition of Chiron.

"Novartis is committed to MS and to providing effective treatments for patients with this disease," said Trevor Mundel, MD, Head of Global Development Functions at Novartis Pharma AG. "The approval of Extavia means we are able to offer the MS community a current standard of care while preparing for the introduction of innovative therapies such as FTY720."

Novartis also recently filed for approval of interferon beta-1b with the US Food and Drug Administration. Launches in the US and EU are planned for the first half of 2009, in line with an agreement with Bayer-Schering that established the opportunity for Novartis to introduce its own branded version of interferon beta-1b.

By the end of 2009, Novartis also plans to file for approval of the innovative oral therapy FTY720 (fingolimod). Results of an ongoing Phase II study extension presented in April show sustained benefits in patients with relapsing MS after three years of treatment with FTY720. Data showed that 68-73% of patients in the study remained free from relapses after three years' continuous treatment[3].

A number of other compounds for treating MS are also in early stage development by Novartis.

Multiple sclerosis is the most common disorder of the central nervous system in young adults2. It is a progressive and debilitating disorder caused by the destruction of myelin, which helps neurons carry electrical signals in the brain. MS causes problems with muscle control and strength, vision, balance, sensation and cognitive function2. MS typically presents in relapsing forms involving acute self-limiting attacks of neurological dysfunction (or "relapses") followed by complete or partial restoration of functions[4].

In the EU, Extavia is approved for patients with relapsing-remitting MS, the most common form of the disease involving relapses followed by complete or partial restoration of function, and for a steadily worsening form of the disease known as secondary progressive MS with relapses.

In addition, Extavia is approved to treat patients with early MS who:

Have experienced a single episode involving loss of myelin (or "demyelinating event")
Have an active inflammatory process that is severe enough to need treatment with intravenous corticosteroids, if alternative diagnoses have been excluded
Are at high risk of developing clinically definite MS.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "plans", "will", "should" or similar expressions, or by express or implied discussions regarding potential new indications, labeling or regulatory filings or approvals for Extavia® or regarding potential future revenues from Extavia®. Such forward-looking statements reflect the current views of the management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Extavia® to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Extavia® will be approved for any additional indications or labeling by the European Commission or that Extavia will be approved for any indications in any additional markets. There can also be no guarantee that Extavia® will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Extavia® could be affected by, among other things, introduction of new MS therapies, unexpected regulatory actions or delays or government regulation generally or involving Extavia®, interferon beta-1b; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Novartis AG provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on growth areas in healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, and consumer health products. Novartis is the only company with leading positions in these areas. In 2007, the Group's continuing operations (excluding divestments in 2007) achieved net sales of USD 38.1 billion and net income of USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 98,000 full-time associates and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.

References
[1] Data on file. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc; 2007.
[2] Multiple Sclerosis International Federation at www.msif.org Accessed 15 May 2008.
[3] Comi G et al. Oral FTY720 (fingolimod) in patients with relapsing multiple sclerosis. 3-year extension shows sustained low relapse rate and MRI activity. Abstract presented at 60th annual meeting of American Academy of Neurology, Chicago, 12-19 April 2008.
[4] National Multiple Sclerosis Society at www.nationalmssociety.org, Accessed 15 May 2008.
# # #

Novartis Media Relations

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