COPAXONE® Significantly Decreases Disease Activity in Patients Who Switched from Interferon Beta (INFb) Due to Development of Neutralizing Antibodies

Relapsing-remitting multiple sclerosis Patients Experience Significantly Extended Time to First Relapse Compared to NAbs-Positive IFNb Patients

JERUSALEM--(BUSINESS WIRE)--Patients treated with interferon beta (IFNb) who have experienced loss of efficacy due to the development of neutralizing antibodies, had a significant delay in time to first relapse (p=0.0389) following switch to COPAXONE®. In addition, patients who were switched to COPAXONE® experienced reduction in mean annual relapse rate compared to pre-IFNb treatment. Results from this retrospective comparative study were presented at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Prague.

“The development of NAbs occurs in up to 30 percent of RRMS patients treated with IFNb therapy and has been shown to impair the therapeutic effectiveness of IFNb therapies,” said Dr. Antonio Bertolotto, Centro Riferimento Regionale Sclerosi Multipla (CReSM) and Laboratorio di Neurobiologia Clinica, Ospedale Universitario San Luigi, Orbassano, Italy. “In our MS Center patients with NAbs persistently positive and without IFNb biological activity measured by MxA (Myxovirus A) mRNA (Messenger Ribonucleic Acid) and with a Relapse Rate/year of 1 or less where switched to COPAXONE®. These data suggest that physicians should discontinue IFNb treatment in patients who test positive for NAbs and that they should strongly consider switching patients to COPAXONE®, as it improves clinical measures of disease activity”.

About the Study

The retrospective comparative analysis evaluated changes in relapse rate, proportion of relapse-free patients and time to first relapse between IFNb and COPAXONE® in NAbs-positive patients who were switched to COPAXONE®. Patients evaluated in the analysis (n=19) were identified as having persistent NAbs positivity (at least 2 months consecutive 3 months apart sera), abolished bioactivity of IFNb therapy, as measured by MxA mRNA, low disease activity during IFNb treatment (one or fewer relapse in the last year of IFNb treatment) and at least 12 months of follow up after COPAXONE® introduction.

The mean annualized relapse rate in pre-IFNb, IFNb NAbs-negative, IFNb NAbs-positive and COPAXONE® (glatiramer acetate injection) treatment periods were respectively 0.98, 0.1, 0.32, 0.21 (p<0.001 for pre-IFNb treatment period versus each other treatment period; p=NS for other group analyses). The time to first relapse was significantly different among the IFNb NAbs-negative, IFNb NAbs-positive and COPAXONE® treatment periods, with a significant difference between the IFNb NAbs-positive and COPAXONE® treatment periods (50th percentile: 17.8 versus 37.9 months; 75th percentile: 6.9 versus 12.9 months; p=0.0389).

For additional details on the study design and results, please refer to the poster “Glatiramer acetate reduces disease activity in NAbs to IFNb-positive patients,” by M. Capobianco, A. Sala, S. Malucchi, M. Caldano, A. Di Sapio, F. Sperli, A. Oggero, F. Marnetto, P. Valentino, L. Granieri, F. Gilli, A. Bertolotto.

About MS

Multiple Sclerosis (MS) is the leading cause of neurological disability in young adults. It is estimated that 400,000 people in the United States are affected by this disease, and that over one million people are affected worldwide. MS is a progressive, demyelinating disease of the central nervous system affecting the brain, spinal cord and optic nerves.

Patients with MS may experience physical symptoms and/or cognitive impairments, including weakness, fatigue, ataxia, physical dysfunction, bladder and bowel problems, sensory effects, and visual impairment. MS also has a significant impact on the sufferers' social functioning and overall quality of life.

About COPAXONE®

Current data suggest COPAXONE® (glatiramer acetate injection) is a selective MHC (Major Histocompatability Complex) class II modulator. 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, or 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 47 countries worldwide, including the United States, Canada, Mexico, Australia, Israel, and all European countries. In Europe, COPAXONE® is marketed by Teva Pharmaceutical Industries Ltd. and sanofi-aventis. In North America, COPAXONE® is marketed by Teva Neuroscience, Inc.

Teva Pharmaceutical Industries Ltd., headquartered in Israel, is among the top 20 pharmaceutical companies in the world and is the 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.

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. (NASDAQ: TEVA), headquartered in Israel, is among the top 20 pharmaceutical companies in the world and is the 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 75 percent of Teva's sales are in North America and Europe.

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 Teva’s 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: Teva`s ability to successfully develop and commercialize additional pharmaceutical products, the introduction of competing generic equivalents, the extent to which Teva may obtain U.S. market exclusivity for certain of its new generic products and regulatory changes that may prevent Teva 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 Famvir®, 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, Teva’s ability to successfully identify, consummate and integrate acquisitions, 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 Teva’s Annual Report on Form 20-F and its other filings with the U.S. Securities and Exchange Commission. Forward-looking statements speak only as of the date on which they are made and the Company undertakes no obligation to update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

Contacts
Teva Pharmaceutical Industries Ltd.
Dan Suesskind, 972-2-941-1717
Chief Financial Officer
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Teva Pharmaceutical Industries Ltd.
Teva North America
George Barrett, 215-591-3030
Corp. Exec. V.P. - Global Pharmaceutical Markets
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Treosulfan Effective and Safe for Active Secondary Progressive Multiple Sclerosis: Presented at ECTRIMS

By Chris Berrie

PRAGUE, CZECH REPUBLIC -- October 18, 2007 -- Treosulfan appears to be safe and well tolerated, and shows both clinical and radiological efficacy in patients with secondary progressive multiple sclerosis (SPMS), according to a two-center, nonrandomized, noncontrolled, open-label study.

These findings were presented here on October 13 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Treosulfan, a cytostatic bifunctional alkylating agent, has been available for the treatment of ovarian cancer for several years, and more recently it has been shown to reduce the severity of autoimmune encephalomyelitis in an animal model. At the same time, it is known to reduce proliferative capacity and increase apoptosis in human peripheral blood mononuclear cells, and to inhibit migration of immune cells.

Heinz Wiendl, MD, Coordinating Investigator and Head, Clinical Research Group, Department of Neurology, University of Wuerzburg, Wuerzburg, Germany, and colleagues evaluated the safety and efficacy of treosulfan in patients with SPMS who have failed or do not qualify for treatment with conventional immunomodulatory agents.

After patient screening, the study design provided an initial induction phase of 3 months with monthly pulses of treosulfan starting at 7 g/m2, with dose escalation to 8 g/m2. This was accompanied by clinical evaluations every 4 weeks, with magnetic resonance imaging (MRI) at baseline and at the end of this induction phase.

This phase was followed by a maintenance phase for 1 year, with 3-monthly pulses of treosulfan, and accompanied by 3-monthly clinical and MRI analyses. In both induction and maintenance, the clinical assessments included expanded disability status scale (EDSS) and MS Functional Composite (MSFC), along with blood and urine analyses.

A total of 21 patients with confirmed SPMS participated in the study, divided according to the safety (n = 11) and efficacy (n = 20) sets. These patients were in a phase of secondary progression of the disease, as seen from the mean duration of SPMS of 4.3 and 4.6 years, respectively. Their mean MS durations since the first manifestation were 16.6 and 17.2 years, respectively, and they were still under active disease according to the number of attacks they had in the previous year (means, 1.4, 1.4). Their mean EDSS scores were 4.95 and 5.05, respectively.

"All of the patients either stabilized or even improved over the observation period of 1 year," Dr Wiendl indicated. The annual relapse rate of 1.5 prior to study entry decreased significantly to 0 by the end of the study year (P <.016).

Within the MRI analyses, there was a trend for a reduction in Gd-enhancing lesions, although, as Dr. Wiendl said, "What we saw by the end of this study was that some of these patients seemed to be having recurring activity, which could be an indication that the 3-monthly maintenance pulses are not sufficient to be anti-inflammatory."

Therefore, the researchers concluded that not only was treosulfan safe and well tolerated, but nine of the 11 patients remained on treosulfan for the complete study period, during which they showed clinical stabilization or improvements, as judged by their EDSS and MSFC scores. Furthermore, no clinical relapses were seen during the treatment period, and the mean numbers and volumes of their T2 and T1 lesions did not change during the year of treatment.

These results have thus moved things forward with the establishing of a randomised phase 2 study, which is currently in recruitment, Dr. Wiendl said.

Funding for this study was provided by Medac GmbH.


[Presentation title: Treatment of Active Secondary Progressive Multiple Sclerosis With Treosulfan. Abstract 75A]

Mitoxantrone as Induction Followed by Interferon Beta-1b Versus Interferon Beta-1b: Presented at ECTRIMS

By Chris Berrie

PRAGUE, CZECH REPUBLIC -- October 18, 2007 -- Mitoxantrone induction in combination with methylprednisone prior to interferon beta (IFNbeta) treatment in patients with aggressive relapsing-remitting multiple sclerosis (RRMS) reduces the risk of developing fixed disability and increases relapse-free periods when compared with IFNbeta prior to methylprednisone.

These findings are from a multicentre, randomised, prospective, controlled, study presented here on October 13 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

The study's principal investigator, Gilles Edan, MD, and Professor of Neurology, Istitut des Neurosciences Cliniques de Rennes, Rennes, France, presented the findings on behalf of the French-Italian Mitoxantrone-Interferon-beta-1b Study Group.

Although IFNbeta-1b can reduce relapse frequencies and new lesions on magnetic resonance imaging (MRI), the magnitude of these effects remains small, providing around 30% benefit. Furthermore, in the longer term of 3 to5 years, these beneficial effects can be lost, particularly for the 35% of patients with RRMS who develop neutralizing antibodies while under IFNbeta treatment.

"Mitoxantrone has a strong, rapid and sustained impact on the inflammatory processes, but its potential toxicity limits the duration of its prescription," Dr. Edan said. Therefore, Dr. Edan and colleagues conducted a study to determine whether the use of mitoxantrone induction prior to IFNbeta-1b therapy can provide further clinical benefits.

The main inclusion criteria were age 18 to 45 years, confirmed diagnosis of MS using Poser criteria and as defined by MRI. For disease status of aggressive RRMS, there was the requirement for two or more relapses in the preceding 12 months, at least one Gd+ lesion on MRI, and an expanded disability status scale (EDSS) score of 2.5 to 5.5 (significant disability).

Exclusion criteria were pregnancy and breast feeding, nonuse of efficient contraception, previous global immunosuppression, use of other specific agents, and associated disease.

The primary endpoint was time to 1 or greater-point increase on the EDSS during the 3 years of the study. There were also secondary endpoints of relapse frequency, relapse-free patients, time to first relapse after inclusion, and safety.

Of 123 patients randomized in the study, 109 were treated and analyzed, constituting the intention-to-treat population. The study design provided randomization to one of two treatment arms after 12 months of followup.

The 55 patients in the first arm started at baseline with mitoxantrone 20 mg/month plus methylprednisone 1 g/month for the first 6 months of treatment. They then had a 3-month break from treatment (months 7-9), followed by interferon 250 mcg SC every other day from months 10 to 36.

The 54 patients in the second arm started at month 0 with methylprednisone 1 g/month in combination with IFNbeta-1b. As with group 1, methylprednisone was stopped after 6 months, while IFNbeta-1b continued for the full 36 months of the study.

Patients in the two groups had similar mean ages (33.2 vs 32.2 years, respectively) and gender distribution (male 34.6% vs 33.3%, respectively).

At baseline, the disease characteristics across treatment groups 1 and 2, respectively, were not significantly different, including duration of MS (6.6 vs 5.1 years), time from last relapse to M0 (3 vs 3 months), annual relapse rate (2.65 vs 2.83) and EDSS score (4.1 vs 3.8).

The primary endpoint was time for a 1-point increase in EDSS (acquisition of fixed disability) within the 36 months of the trial. "This time was clearly longer in the group of patients using mitoxantrone and interferon beta," Dr. Edan said, and thus, there was mitoxantrone group obtained significant benefit compared with group 2 (P =.008). As only five of the total 19 patients who acquired this fixed disability by month 36 were in group 1, this represented a significant 65% reduction in clinical worsening in the mitoxantrone-pretreated patients (P <.024).

When variations in EDSS score were analyzed from baseline to the last recorded scores during the treatment period, the mitoxantrone group saw a small but significant decrease in mean EDSS score from 4.1 to 3.6 (P <.006), whereas in the absence of mitoxantrone there was no significant change (from 3.8 to 3.7).

For the annual relapse rate under study treatment, there was again a large, 61.5%, significant benefit with the use of mitoxantrone (annual relapse rate: group 1, 0.44; group 2, 1.14; P <.003). When further analyzed as annual relapse rate during the IFNbeta-1b alone treatment, benefits for mitoxantrone were again seen compared with treatment without mitoxantrone (group 1, 0.50; group 2, 1.14; P <.007).

Patients in the mitoxantrone group also had significantly improved time to first relapse from baseline (P <.002). Similarly, there was a significant increase in the percentage of relapse-free patients in group 1 over group 2 (53% vs 26%; P =.01).

Finally, the researchers also tested mitoxantrone benefits at the patient disability levels. Although not a pre-planned analysis, this was achieved in a subgroup analysis of EDSS at baseline, divided according to an EDSS of 4.0, and demonstrated a significant benefit for both the use of mitoxantrone and an EDSS score less than 4 at baseline (P <.02).

The safety analysis showed significantly more adverse events in the mitoxantrone group compared with the group not treated with mitoxantrone. These comprised upper respiratory tract infection (45.4% vs 24.1%, respectively; P <.02), leucopenia (36.4% vs 16.7%, respectively; P <.02) and nausea (21.8% vs 7.4%, respectively; P <.02).

"However, these [adverse effects] are exactly what you might expect from adding mitoxantrone to this treatment, and there was no serious adverse effect in this study," added Dr. Edan.

Thus, he concluded, this induction treatment of mitoxantrone combined with methylprednisone provides clinical benefits for patients with aggressive RRMS that include decreases in both acquisition of fixed disability and relapse rates.


[Presentation title: Comparison of Two Therapeutic Strategies in Aggressive Relapsing-Remitting MS: Mitoxantrone as Induction for 6 Months Followed by Interferon Beta-1b Versus Interferon Beta-1b. A 3-Year Randomised Trial. Abstract 74]

Rituximab in Adults With Relapsing-Remitting Multiple Sclerosis: Presented at ECTRIMS

By Chris Berrie

PRAGUE, CZECH REPUBLIC -- October 17, 2007 -- A single course of rituximab is safe and well tolerated, and compared with placebo, significantly reduces magnetic resonance imaging (MRI) and clinical evidence of inflammatory activity in patients with relapsing-remitting multiple sclerosis (RRMS), according to a multicenter, randomized, placebo-controlled, phase 2 trial.

The findings were presented here on October 13 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

"For a decade or more, people have mostly looked at treatment that affects T cells in MS, although within the past 10 years there has actually been increased interest in B cells and their products," said principal investigator Emmanuelle Waubant, MD, PhD, Associate Professor of Neurology, Department of Neurology, University of California at San Francisco, San Francisco, California.

Past research has shown that the action of the genetically-engineered chimeric monoclonal anti-CD20 antibody rituximab, in its depletion of pre-B and B cells via binding to their CD20 antigen, could provide an alternative approach in the modulation of MS pathophysiology.

"So this is a proof-of-concept study, to determine whether, in human MS, targeting B cells has an impact on the course of the disease," Dr. Waubant said. The design aim was to evaluate the safety and efficacy of a single treatment cycle of rituximab over 48 weeks in patients with RRMS.

Study subjects were 18 to 55 years old and had a confirmed diagnosis of MS, at least one relapse in the previous year, and an expanded disability status scale (EDSS) score of 0 to 5. They were excluded if they had secondary progressive, primary progressive, or progressive-relapsing MS, and patients who had received various previous treatments were also excluded.

The 104 patients with RRMS enrolled were randomized to placebo (n = 35; mean age, 41.5 years; male, 17.1%) or rituximab 1,000 mg IV infusion on days 1 and 15 (n = 69; mean age, 39.6 years; male, 24.6%).

The primary endpoint was the total number of Gd-enhancing T1 brain lesions on serial MRI scans at weeks 12, 16, 20, and 24. A series of exploratory efficacy outcome measures were used as secondary endpoints: proportion of patients relapsing; annualized relapse rate; total number of new Gd-enhancing T1 lesions; and annualized relapse rate and T2 lesion volume change.

Baseline clinical characteristics between placebo and rituximab treatment groups were essentially the same with respect to number of relapses in the previous year (about 75% of patients had one relapse), mean EDSS score (2.7 vs 2.8, respectively), MS therapy in the previous 2 years (generally glatiramer acetate, interferon beta-1a, and methylprednisone), and lesion counts and volumes.

When compared with the placebo group, rituximab treatment satisfied the primary endpoint, with a significant 91% reduction in mean total Gd-enhancing lesion counts at weeks 12, 16, 20, and 24 (5.5 vs 0.5, respectively; P <.001). Significance was reached at week 12 (P =.003) and continued through the full 48 weeks of monitoring (P <.0001).

For the secondary endpoints, rituximab significantly reduced the number of new Gd-enhancing lesions at weeks 12, 16, 20, and 24, as compared with placebo (P <.001). From week 12, rituximab significantly reduced the number of new Gd-enhancing lesions at each assessment (P =.002 to P <.001).

Rituximab treatment also showed a trend in these patients towards lower annualized relapse rates that reached significance compared with placebo by week 24 (0.84 vs 0.37, respectively; P =.04), although this significance did not carry through to week 48.

For the safety assessments, while all other safety aspects examined were the same across the treatment groups, after the first infusion there were significantly greater infusion-associated adverse events with rituximab than placebo (78.3% vs 40.0%, respectively). However, this effect was reversed after the second infusion (40.0% vs. 20.9%, respectively).

Overall, rituximab was safe, well tolerated, and efficacious through the full 48 weeks of follow-up.

"We demonstrate a very rapid effect of depletion of B cells on the course of MS, measured by MRI, and clinical course, which suggests that it is probably not an effect that is promoted by interfering with the antibodies or immunoglobulin in MS, but it's more likely to be through B cells and their direct cellular effects on T cells and cytokines," Dr. Waubant indicated.

Funding for this study was provided by Genentech Inc.


[Presentation title: Safety and Efficacy of Rituximab in Adults With Relapsing-Remitting Multiple Sclerosis: Results of a Phase 2, Placebo-Controlled, Multicentre Trial Through 48 Weeks. Abstract P554]

Scientists Show Monoclonal Antibody Leads to Repair of Myelin Sheath in Laboratory Study of Multiple Sclerosis

HAWTHORNE, N.Y.--(BUSINESS WIRE)--Oct. 16, 2007--Researchers at Mayo Clinic have presented details from a preclinical study showing that a recombinant human monoclonal antibody, administered in a single low dose in a laboratory mouse model of multiple sclerosis, can repair myelin, the insulating covering over nerve fibers in the central nervous system.

The study was presented on October 9, 2007 at the American Neurological Association meeting in Washington, D.C.

"We are excited to be collaborating with Mayo on the development of this therapy," noted Andrew R. Blight, Ph.D., Chief Scientific Officer at Acorda. "The options for treatment of MS are still quite limited, and a new approach that could repair damage to the central nervous system would represent an important advance for the individuals who live with this disease."

In multiple sclerosis and some other disorders of the central nervous system, the immune system attacks and destroys the myelin sheath, causing the nerve to lose its ability to conduct electrical impulses from the brain to the body, resulting in the disabilities associated with those conditions.

The antibody, which was genetically engineered for large-scale production, binds to myelin and the surface of cells in the brain and spinal cord, triggering the cells to begin the repair process called remyelination. The study was conducted using a laboratory mouse model of chronic progressive multiple sclerosis in humans. The antibody was delivered alone and in combination with the steroid methylprednisolone; remyelination was detected in both instances.

The antibody is being developed by Mayo Clinic and Acorda Therapeutics. Under a license agreement between Acorda and Mayo Clinic, Acorda holds exclusive worldwide rights to certain patents and other intellectual property for this antibody related to use and treatment of central nervous system disorders, including multiple sclerosis. Both Acorda and Mayo will be working on the steps leading to a future Investigational New Drug Application (IND) and a Phase 1 clinical trial.

About Multiple Sclerosis

Multiple sclerosis is a chronic, usually progressive disease of the central nervous system in which the immune system attacks and destroys the structure, and therefore degrades the function, of nerve cells. According to the National Multiple Sclerosis Society, approximately 400,000 Americans have MS, and every week about 200 people are newly diagnosed. 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.

The NMSS estimates the direct costs of medical care for MS patients in the United States to exceed $6 billion annually. Additionally, a recent 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 or exacerbations. 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.

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(TM) (tizanidine hydrochloride), a short-acting drug for the management of spasticity. Acorda's lead clinical product, Fampridine-SR, is in a 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 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 Acorda Therapeutics' ability to successfully market and sell Zanaflex Capsules, the risk of unfavorable results from future studies of Fampridine-SR, delays in obtaining or failure to obtain FDA approval of Fampridine-SR, 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:
Erica Wishner, 914-347-4300 ext. 162
ewishner@acorda.com
or
Investor:
Tierney Saccavino, 914-347-4300 ext. 104
tsaccavino@acorda.com

SOURCE: Acorda Therapeutics

Fluoxetine Shows Promise in Multiple Sclerosis

News Author: Thomas S. May
CME Author: Laurie Barclay, MD

October 16, 2007 (Prague, Czech Republic) — Fluoxetine (Prozac) may help reduce the number of new brain lesions in patients with multiple sclerosis (MS), according to a study presented here at the ECTRIMS 2007: 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis.

The study, which was conducted by Jop P. Mostert, MD, and colleagues at the University of Groningen, the Netherlands, shows a trend toward a reduction in new enhancing lesions with fluoxetine treatment in patients with relapsing-remitting or relapsing secondary progressive MS.

Why Fluoxetine?

Fluoxetine, a selective serotonin reuptake inhibitor, was approved by the US Food and Drug Administration in 1987 and is frequently prescribed for the treatment of various psychiatric disorders, including major depression. However, fluoxetine also has a number of immunomodulatory effects, and previous studies have indicated that it might be beneficial for patients with MS, Dr. Mostert said in his presentation.

One of these earlier studies, which was first presented at the 1997 Annual Meeting of the American Association of Neurology, showed that fluoxetine reduced disease activity in experimental autoimmune encephalomyelitis, the animal model of MS, Dr. Mostert noted. "Furthermore, psychiatrists already reported in 1991 reduced MS in patients using fluoxetine," he added.

Previous research has also found that astrocytes in patients with MS lack beta-2 adrenergic receptors, and this leads to decreased cyclic adenosine monophosphate (cAMP) production, which in turn contributes to the initiation of the inflammatory cascade that eventually results in demyelination, Dr. Mostert explained. Because fluoxetine is able to increase the amount of cAMP in the astrocyte, the researchers hypothesized that the drug could help compensate for the loss of beta-2 adrenergic receptors and thus, reduce the amount of inflammation in MS.

Fewer New Lesions

To test their hypothesis, Dr. Mostert's team enrolled 40 patients (age 18 - 65 years) with relapsing-remitting or relapsing secondary progressive MS in a randomized, double-blind, placebo-controlled trial, with a duration of 24 weeks. Half of the patients were given fluoxetine (20 mg/day), whereas the remaining subjects received placebo.

The primary end point was the cumulative number of new gadolinium-enhancing lesions on T1-weighted magnetic resonance imaging (MRI) of the brain performed at weeks 4, 8, 16, and 24. Secondary outcome measures included changes in the Expanded Disability Status Scale (EDSS) and in the Multiple Sclerosis Self-Efficacy Scale (MSSE) from baseline to week 24.

The investigators found that the study drug was generally well tolerated, with only 1 patient dropping out because of adverse effects (nausea) in the treatment group. One patient also dropped out from the placebo group, leaving 19 completers in each group.

Regarding the primary end point, the results show that there was a trend toward a reduction in the number of new enhancing lesions in patients treated with fluoxetine. The mean (SD) cumulative number of new enhancing lesions during the 24 weeks of treatment was 1.84 (2.9) in the fluoxetine-treated patients and 5.16 (8.6) in the control subjects (P = .15).

At week 4, the cumulative number of new enhancing lesions was "quite comparable" in the two 2 groups, pointed out Dr. Mostert. He emphasized, however, that in the latter part of the trial, there was a steady increase in new lesions in the placebo group, while the number of lesions in the fluoxetine-treated patients remained relatively stable. Restricting the analysis to the last 16 weeks showed a "nearly significant" reduction in the cumulative number of new enhancing lesions and a higher number of patients without new enhancing lesions (63% vs 26%; P = .02).

Commenting on the study, session cochair Roland Liblau, MD, PhD, from Toulouse University Hospital in France, noted that the researchers used "a very interesting approach," because fluoxetine has a very good safety profile.

"It has been used in hundreds of thousands of patients, so we know it's safe," he told Medscape Neurology and Neurosurgery. "The possibility that it has even a slight effect in multiple sclerosis would be very interesting," he added. "The data showed a trend toward efficacy in MS, and I would strongly encourage further trials involving more patients."

This study was an investigator-initiated trial, with no pharmaceutical industry funding.

Medscape Medical News 2007. ©2007 Medscape


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Interferon Beta-1a and Glatiramer Acetate in Relapsing-Remitting Multiple Sclerosis: Presented at ECTRIMS

By Chris Berrie

PRAGUE, CZECH REPUBLIC -- October 16, 2007 -- Interferon beta-1a (IFNbeta-1a) has no significant efficacy benefits or safety issues over the polypeptide glatiramer acetate for patients with relapsing-remitting multiple sclerosis (RRMS), according to results from a multicentre, randomised, comparative, assessor-blinded, open-label trial.

Principal investigator Dan D. Mikol, MD, PhD, Associate Professor of Neurology, Department of Neurology, University of Michigan, Michigan, United States, presented the findings here on October 14 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

This was the first head-to-head study of IFNbeta-1a and glatiramer acetate.

"The planned sample size was 736 patients, and included in the expectations was that there would be an 80% power to detect a 30% difference between these two agents in the primary outcome, which was time to first relapse."

Dr. Mikol and colleagues enrolled 764 patients aged 18 to 60 years and diagnosed with relapsing-remitting MS by McDonald criteria, had experienced one or more attacks within the prior 12 months, and were clinically stable or had improving neurological state in the prior 4 weeks. They also had magnetic resonance imaging (MRI) evidence of brain lesions and an expanded disability status scale (EDSS) of 0 to 5.5.

Following prestudy evaluation, 386 patients were randomised to 44 mcg of subcutaneous IFNbeta-1a three times weekly and 378 patients to 20 mg of subcutaneous glatiramer acetate once daily, both for 96 weeks.

Key baseline clinical characteristics in the two treatment groups were similar for time since first relapse (5.93 years, 6.55 years, respectively), number of T1 Gd-enhancing lesions (1.47, 1.65), T1 Gd-enhanced lesion volume (254.81, 241.99 mm3), and T2 lesion volume (7915.61, 7560.38 mm3).

However, 60% of patients in the interferon arm had more than one relapse in the previous 24 months compared with 71% in the glatiramer acetate arm, Dr. Mikol noted.

The primary endpoint was time to first relapse; the predefined secondary endpoints were mean number of T2 active (new or enlarging) lesions per patient per scan, and mean number of T1 Gd-enhancing lesions per patient per scan.

Tertiary endpoints were: mean number of combined unique active (CUA) lesions per patient per scan, and proportion of scans per patient with CUA lesions; clinical assessment of relapse rate, and proportion of patients free of relapses.

For the primary, secondary and some of the tertiary analyses, results were also stratified by prespecified subgroups.

At 96 weeks, the researchers found no significant differences between the IFNbeta-1a and glatiramer acetate treatment arms in terms of the primary outcome (hazard ratio [HR], 0.943; 95% confidence interval [CI], 0.74-1.21; P =.643). Dr. Mikol noted that these two patient groups experienced 45% fewer relapses than expected.

Due to this slow relapse rate, the researchers included a series of prespecified subgroup analyses relating to baseline T1 Gd-enhancing lesions (0 vs >=1), relapses 2 years prior to baseline (1 vs >=2), geographic region (non-Russia vs Russia), EDSS at baseline (<=median 2.0 vs >median 2.0), baseline T2 lesion volume (<=median 3707.5 vs >median 3707.5 mm3), and MS therapy in the prior 6 months (e.g. steroids; no vs yes).

The only subgroup where the researchers found a significant difference at the 96-week evaluation was EDSS at baseline in favor of IFNbeta-1a (n = 207) over glatiramer acetate (n = 211) in the group with EDSS scores below the median (HR, 0.648; 95% CI, 0.45-0.94; P =.022)

Although the researchers observed no significant difference between IFNbeta-1a and glatiramer in the number of T2 active lesions per patient per scan (0.7 vs 0.8; P =.178), within the prespecified subgroup analyses, they found significantly fewer T2 active lesions in patients treated with IFNbeta-1a both in the subgroup of patients with EDSS scores lower than the median (P =.035) and in non-Russian patients versus Russian patients (P =.043).

Significant benefit in favor of IFNbeta-1a versus glatiramer was seen for the secondary endpoint of T1 Gd-enhancing lesions (0.2 vs 0.4; P <.001) and for mean CUA lesions per patient per scan (0.9 vs 1.2; P =.010). Within the subgroups, IFNbeta-1a was better than glatiramer in patients who were non-Russian (P <.001), had baseline scores that were lower than the median on the EDSS (P <.001), with baseline lesion volume greater than the median (P <.001) and had prior MS therapy (P <.001).

For the tertiary endpoints of mean number of CUA lesions/patient/scan, and proportion of scans/patient with CUA lesions, these both indicated significant benefit for IFNbeta-1a, with mean treatment differences of -0.31 (P =.010) and -5.9 (P =.009), respectively.

Finally, for the annualized relapse rates for IFNbeta-1a and glatiramer acetate, there were no significant differences between these two treatment groups (0.30 vs 0.29; P =.828). "What is intriguing and certainly stands out in this trial is the fact that the relapse rate on-study was so low, 0.3, which is certainly much lower than was anticipated and is different to what has been seen in previous clinical trials," added Dr. Mikol.

Thus Dr. Mikol summarized, "There were no significant difference in primary endpoint of time to first relapse; the safety outcomes were consistent with the known profiles of both treatments; and there was significant difference in favor of IFNbeta-1a for T1 Gd-enhancing lesions and for some of the additional pre-specified subgroup analyses.

Funding for this study was provided by Merck Serono International S.A. and Pfizer Inc.


[Presentation title: The REGARD Trial: A Randomised Assessor-Blinded Trial Comparing Interferon Beta-1a and Glatiramer Acetate in Relapsing-Remitting Multiple Sclerosis. Abstract 119]

Simvastatin Does Not Antagonize Interferon-Beta, Interim Analysis Suggests CME

News Author: Thomas S. May
CME Author: Laurie Barclay, MD


October 15, 2007 (Prague, Czech Republic) — An interim analysis of the Simvastatin as an Add-on Treatment to Interferon-Beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis (SIMCOMBIN) trial has found that simvastatin does not block the anti-inflammatory effect of interferon-beta (IFN-beta) when both of these drugs are taken together by patients with multiple sclerosis (MS).

Results of the interim analysis were presented here by lead investigator Per Soelberg Sørensen, MD, from Copenhagen University Hospital, Righospitalet, Denmark at the 23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis (ECTRIMS).

Rationale for the Study

SIMCOMBIN is an ongoing double-blind, placebo-controlled, randomized, parallel-group, phase 4 study designed to determine if there is any benefit to adding simvastatin to IFN-beta-1a (Avonex, Biogen Idec) in patients with MS. This large, multicenter trial began in February 2006 and is planned to be complete in November 2009.

"Why combine interferon-beta with statins?" Dr. Sorensen asked rhetorically, as he began his presentation. The reason for this, he said, is that statins are potent immunomodulators and have been found to be beneficial in several studies involving animal models of MS. One small, open-label study using human subjects with relapsing-remitting MS reported a more than 40% reduction in both the number and volume of gadolinium-enhancing lesions, after they were treated with simvastatin 60 mg daily for 6 months, he noted.

The main reason for conducting the interim analysis was because of a presentation of a double-blind, placebo-controlled study of atorvastatin in combination with IFN-beta-1a, presented by Gary Birnbaum, MD, from the University of Minnesota, during this year's annual meeting of the American Academy of Neurology (AAN), Dr. Sorenson said. That study reported an increase in the combined composite endpoint of new and enhancing magnetic resonance imaging (MRI) lesions and/or relapses in patients receiving IFN-beta plus atorvastatin vs those receiving IFN-beta plus placebo.

The authors of that study hypothesized that these results might be because statins block the anti-inflammatory effect of IFN-beta. "So this urged us to do this safety analysis," Dr. Sorensen explained.

Safety Analysis

Among 61 patients that had been randomized in the SIMCOMBIN study by April 2007, the authors performed an interim safety study in 47 patients who had been treated for at least 3 months with either simvastatin 80 mg daily or placebo as add-on therapy to INF-beta-1a given intramuscularly at a dose of 30 µg weekly.

A subgroup of 27 patients underwent a safety MRI during May 2007 and an analysis of in vivo IFN-beta bioactivity. The primary outcome measure was IFN-beta bioactivity, as assessed by mRNA expression of the IFN-beta biomarkers MxA and TRAIL. Secondary outcome measures included the annualized relapse rate, time to first relapse, and gadolinium-enhancing lesion and new or enlarged lesions on T2-weighted MRI.

An analysis of the results showed that all 27 patients had a full in vivo response to IFN-beta in MxA and TRAIL mRNA expression studies. The mean observation time on therapy was 6.9 months. The annualized relapse rate in all patients was 0.36, which is comparable to relapse rates found previously in other patient populations treated with IFN-beta. Additionally, there was no statistically significant difference in the time to first relapse between the 2 treatment groups.

"These results led our data safety monitoring board to conclude that there are no safety concerns regarding the continuation of the trial as defined by the protocol, and we encouraged the steering committee to carry on the study as planned," Dr. Sorensen told the audience. "This recommendation was based on our own interpretation of the relapse and MRI data," he added.

Remove the Concern

This interim analysis "successfully removed a concern" regarding any potential antagonistic effects of simvastatin vs. IFN-beta, according to Roland Liblau, MD, PhD, from Toulouse University Hospital, France, who cochaired the session. "I think they did the job properly, and I think they removed the concern that statins might antagonize interferon beta and vice versa," Dr. Liblau told Medscape Neurology and Neurosurgery.

He cautioned, however, that the study is still ongoing, and no conclusions should be drawn on the efficacy of this approach.

"The interim analysis didn't show any significant difference between the 2 groups, but you don't expect at this stage to find differences," he said. "So, in terms of efficacy, we cannot conclude anything. This study was done to remove doubt, and I think the doubt has been removed properly."

Funding for this study was provided by Biogen Idec, maker of Avonex (INF-beta-1a).

23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis: Parallel Session 7 (85). Presented October 13, 2007.

Interferon Beta-1b in Combination With Azathioprine for Secondary Progressive Multiple Sclerosis: Presented at ECTRIMS

By Chris Berrie

PRAGUE, CZECH REPUBLIC -- October 15, 2007 -- The addition of azathioprine to standard treatment with interferon beta-1b (IFNbeta-1b) can be maintained over 2 years with only a mild increase in adverse effects in patients with secondary progressive multiple sclerosis (MS), according to results of a multicentre, randomised, comparative, double-blind study.

Principal investigator Enrico Montanari, MD, Professor in Medicinal Psychology, Department of Internal Medicine, MS Centre, Fidenza, Italy, presented the study findings here on October 12 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Secondary progressive MS is characterised by continuous worsening disability and can be accompanied by relapses after varying periods of relapsing-remitting disease. "With secondary progressive multiple sclerosis there remains no therapy, so from the background of other studies, we decided to investigate this combination therapy," Dr. Montanari said.

The aim of the study was thus to assess the efficacy, safety and tolerability of azathioprine when added to IFNbeta-1b in patients with secondary progressive MS who had an incomplete response to IFNbeta-1b.

The study provides an overall evaluation of illness stabilisation, with the primary endpoint being the variation in MS functional composite (MSFC) over the 2-year treatment period. Secondary endpoints were Expanded Disability Status Scale (EDSS) variability, quality of life (QOL) effects according to the MSQOL-54 Instrument, cytokine and neutralising antibodies levels, and safety.

In the study, there was no significant difference between the two treatment groups in median scores on the EDSS in the previous 2 years. This evaluation considered the two treatment groups combined.

The collective baseline characteristics of the 85 patients who entered the randomisation stage demonstrated a mean age of 46.2 years, and a male/female distribution of 36/64; the EDSS profile range was: 4.0, 30.7%; 4.5, 16.0%; 5.0, 18.7%; 5.5, 5.3%; 6.0, 18.7%; 6.5, 10.7%.

There were no changes from baseline in the 6-month combined mean EDSS score variations over 2 years. Although there was an initial indication of a slight worsening in the MSFC score at 3 months (-0.10), the successive mean variations in the 6-month assessments showed maintenance of stable disease to 2 years (6, 12, 18, 24 months versus baseline): +0.02, +0.08, +0.10, +0.03, respectively.

"With the MSFC that we are using, we also see that with the ambulation index and the arms and connection functions, the results are very interesting because there is a stabilisation of these [measures]," Dr. Montanari noted.

Similarly, MSQoL-54 scores over 2 years of combined treatment show maintenance of a slight decrease from baseline scores at 6, 12, 18, and 24 months, in the composite scores of both physical health (-0.8, -1.0, -1.3, -0.8, respectively) and mental health (-2.0, -2.2, -2.1, -2.9, respectively).

The researchers observed a mild increase in adverse events with azathioprine plus IFNbeta-1b compared with IFNbeta-1b alone that involved gastrointestinal problems, an increase in liver laboratory tests and leucopoenia.

However, with a 63% rate of patient retention at the end of 2 years despite 82.4% of patients experiencing one or more adverse event, the results show good tolerability for the combination and are in line with data from other studies in patients with secondary progressive MS, the researchers noted.

Therefore, although there is a mild increase in adverse effects in the azathioprine group, this combination of IFNbeta-1b and azathioprine demonstrates good stabilisation of clinical evolution in patients with secondary progressive MS, the researchers concluded.


[Presentation title: ASPIRE: Interferon Beta-1b in Combination With Azathioprine for Secondary Progressive Multiple Sclerosis: A 2-Year, Double-Blind, Randomised, Multicentre, Pilot Study. Safety and Drop-Outs Data at 21 Months of Enrolment. Abstract P188]

Retinal Thickness May Augur Brain Atrophy in MS

By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
October 15, 2007

BALTIMORE, Oct. 15 -- A noninvasive scan of the retinal nerve fiber layer may offer clues to the progression of multiple sclerosis, investigators here reported.

In 40 patients with MS and 15 healthy controls, there was a strong, albeit imperfect correlation between minimum retinal nerve fiber layer thickness and the degree of whole brain atrophy as seen on MRI, according to Peter A. Calabresi, M.D., of Johns Hopkins, and colleagues.

When they looked at a subset of patients with relapsing-remitting MS, the researchers found that the correlation between the optical coherence tomography (OCT) retinal scans and brain parenchymal fraction on MRI was even stronger, the authors reported in the Oct. 16 issue of Neurology.



40 y/oF RRMS
BPF 0.7908
Photo Credit: John Hopkins

"This is an encouraging result," said Dr. Calabresi. "MRI is an imperfect tool that measures the result of many types of tissue loss rather than specifically nerve damage itself. With OCT we can see exactly how healthy these nerves are, potentially in advance of other symptoms."

Similar in concept to holography, OCT uses interference patterns of light across a broad spectrum to measure noninvasively the thickness of the retinal nerve fiber layer. Thinning of the retinal nerve fiber layer occurs with various ocular disorders, including macular degeneration, glaucoma, and retinitis pigmentosa.



32 y/oF RRMS
BPF 0.7610
Photo Credit: John Hopkins

In addition to its potential as a disease monitoring tool, optical coherence tomography may also provide valuable insights into MS pathogenesis, suggested Stephen G. Waxman, M.D., Ph.D., and Joel A. Black, Ph.D., from Yale University School of Medicine in New Haven, Conn., in an accompanying editorial.

"Serial evaluations of the retinal nerve fiber layer, using OCT, may prove to be useful for clinical studies on the natural history of MS and also on the response to putative treatments," they wrote. "In addition, however, OCT may permit us to capitalize upon the unique structure of retinal ganglion neurons and their axons so that we can learn more about fundamental mechanisms of neuronal injury in MS."

Dr. Calabresi and colleagues enrolled 40 patients with MS and 15 controls into their study. All patients and controls underwent OCT and cranial MRI scans. The authors estimated brain parenchymal fraction, a measure of whole brain atrophy and partial brain volumes. They created multiple linear regression models to examine the association between OCT and MRI measures of atrophy.

The investigators found that a combination of minimum retinal nerve fiber layer thickness and age of the study participant predicted 21% of the variance in brain parenchymal fraction among all MS patients (P=0.005), but not among controls.

In addition, when they looked at the 20 MS patients who had relapsing-remitting disease, they found that retinal nerve fiber layer and age predicted 43% of the variance in brain parenchymal fraction (P=0.003).



50 y/oM SPMS
BPF 0.7399
Photo Credit: John Hopkins

Among all patients, the partial correlation coefficient for brain parenchymal fraction and retinal nerve fiber layer thickness controlled for age was 0.46 (P=0.003).

For the patients with relapsing-remitting disease, the age-corrected correlation coefficient was 0.69 (P=0.001).

However, there was no association between OCT and MRI findings for the 15 patients with secondary-progressive MS; the remaining five patients had primary progressive MS, but this sample size was too small to detect associations, the authors noted.

"These associations are driven by cerebrospinal fluid volume but not by gray or white matter volume. There is no significant association of these variables among controls," the authors wrote.

They concluded that using OCT to quantify axonal thickness in the retinal nerve fiber layer can provide concurrent information about brain abnormalities as seen on MRI, and called for longitudinal studies to see whether the OCT/MRI correlation could be used to monitor outcomes in clinical trials of neuroprotective agents.

In their editorial, Dr. Waxman and Dr. Black noted that "OCT may contribute to a 'mapping' of pathologic events along the various domains of retinal ganglion neurons. To the degree that these cells are a good model, they may help us to understand neurons as disease targets in MS."

The authors acknowledged that the lack of association in the control group may be a function of the small sample size and relative youth of the controls, especially given that retinal nerve fiber layer thinning and brain volume loss can occur in healthy people later in life and may be associated with one another. They suggested longitudinal studies to further explore that issue.

The study was supported by The Nancy Davis Center and National Multiple Sclerosis Society. Neither the authors nor the editorialists had any conflicts of interest to declare.
Additional Multiple Sclerosis Coverage

Primary source: Neurology
Source reference:
Gordon-Lipkin E et al. "Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis." Neurology 2007; 69: 1603-1609

Drug body's advice against provinces paying for MS drugs seen as unfair

TORONTO - An expert panel's advice that provinces and territories not cover the cost of two Multiple Sclerosis drugs creates a system of two-tiered care, MS advocates say.

They view the recommendation as leaving people with the disease, who don't have private drug insurance, unable to afford medication that could slow progression of the condition and ease the pain they suffer.

Late last month, the Common Drug Review advised that governments not put the MS pain medication Sativex on the list of medicines that provincial and territorial drug plans cover for eligible people. That follows a "do not list" recommendation issued in the spring for Tysabri, a drug that slows progression of the disease.

Those decisions put these drugs out of reach for many people with MS, an expert and a spokesperson for the MS Society argue.

"It's frustrating, because as an MS doctor, I would like my patients that are on public assistance to have the same access to MS treatments as patients with private drug plans," says Dr. Paul O'Connor, head of the MS clinic at Toronto's St. Michael's Hospital.

"And they most certainly do not."

Private insurance programs, which are generally provided as an employment benefit, may cover the costs of the medications for people with MS who have drug coverage. But the reality of MS is that the progressive and debilitating nature of the disease robs many people with it of the ability to hold down a job.

"We're talking about a population that has challenges staying in the workplace, has challenges in terms of maintaining their status on private insurance," says Jon Temme, vice-president of research for the Multiple Sclerosis Society of Canada.

"Because the nature of the disease is such that over time and with the disease progressing a significant number of people - we estimate up to 80 per cent - are unable to work full time."

"Anything that keeps (medication) options away from them is of concern to us."

The MS Society estimates that between 55,000 and 75,000 Canadians have MS.

The Common Drug Review is a body set up by the federal, provincial and territorial governments to assess the efficacy and cost-effectiveness of new medications.

It convenes an expert panel comprised of people with backgrounds in medicine, epidemiology, clinical reviews and statistics to comb through the evidence - published and unpublished - on how well a drug works, how well it works compared to other available medications and how cost-effective it is.

"None of the decisions are taken lightly," says Sandy Pagotto, director of the Common Drug Review.

"Definitely the committee considers the evidence very seriously during their deliberations. It's a very strong process."

The body only has the power to recommend. It is up to individual provinces and territories to decide whether to heed or ignore the advice. But Temme said in the MS Society's experience, provinces may ignore advice to cover the cost of a drug, but rarely disagree when the Common Drug Review advises against paying for a medication.

"In our office we sometimes say that in the Common Drug Review, 'Yes' means 'Maybe' and 'No' means 'No,"' he says.

In the cases of Sativex (a cannabinoid-based product administered in an oral spray) and Tysabri (a once-a-month intravenous infusion) the body urged provinces not to list the high-cost medications, saying there were other, more cost-effective options.

O'Connor says that while some patients experience better pain relief with Sativex than with other available pain control drugs, the real loss is Tysabri.

The drug, which costs in the range of $40,000 a year, was approved for use in patients who have not responded to other available treatments aimed at slowing the progression of the disease. Temme says for some MS patients, Tysabri represents "the last option in terms of their ability to treat their MS."

And for others, including Ronalee Newham, the drug is superior to the alternatives. Newham, 29, is from Portage La Prairie, Man. She is the mother of two young children and she has been battling MS for the past 6½ years.

Newham was enrolled in a clinical trial for Tysabri, and took the drug for two years while in the trial. The symptoms of her disease virtually melted away while she was getting the drug, including the fatigue that at times can force her to sleep up to 18 hours a day.

A former competitive swimmer, Newham was able to return to the pool while on the drug, swimming 80 laps a day. But when the trial ended, so did her access to the drug. The drug plan she receives through her job - she works as support staff in a school - hasn't yet covered Tysabri, so she's on what she calls the "second best" treatment.

"I would have to say that on a really, really good day, I could probably go swim 20 laps as opposed to the 80 I would do on Tysabri," she says wistfully.

Newham wonders whether those studying the cost-effectiveness of the drug have factored in the savings accrued when people with MS spend less time in hospital, less time on disability and more time in the workforce, paying taxes.

"It doesn't make sense to me," she says.

"It's frustrating, that's for sure, to know where I could be and to know where I'm at. And that the only thing that's stopping me from being as good as I can be is money. It's very frustrating."

Daclizumab Reduces Brain Lesions in Patients With Active, Relapsing Multiple Sclerosis on Interferon-Beta Therapy: Presented at ECTRIMS

By Chris Berrie PRAGUE, CZECH REPUBLIC -- October 13, 2007 -- The addition of the humanized antihuman interleukin-2 (IL-2) alpha receptor chain (CD25) antibody daclizumab to interferon beta (IFNbeta) therapy is safe and well tolerated by patients with multiple sclerosis (MS), and is associated with a significant reduction in new or enlarged Gd+ lesions. Coinvestigator Xavier Montalban, MD, Head, Neuroimmunology Clinic, Vall d'Hebron University Hospital, Barcelona, Spain, presented the results of the multicenter, randomized, double-blind, placebo-controlled, phase 2 CHOICE study here at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Daclizumab blocks interleukin 2 (IL-2)alpha receptor-mediated T- and B-cell activation, Dr. Montalban said in his presentation on October 12. Open-label studies of patients with relapsing multiple sclerosis who were refractory to IFNbeta therapies indicated that daclizumab reduced the number of new brain lesions. For the CHOICE study, Dr. Montalban and colleagues enrolled a total of 230 patients (aged 18-55 years) with an MS diagnosis confirmed using McDonald criteria, on at least 6 months of stable IFNbeta treatment, who satisfied the following criteria: expanded disability status scale (EDSS) of 5 or greater at screening; and one or more relapses or qualifying magnetic resonance imaging (MRI) scans within 12 months of screening. Patients were randomized to three treatment combinations with background IFNbeta: 77 received placebo, 78 received daclizumab 1 mg/kg SC every 4 weeks (low-dose); 75 received daclizumab 2 mg/kg every 2 weeks (high-dose). They were all treated for 24 weeks and were followed for 48 weeks. "Ninety percent completed the treatment period, which means that the drop-out was very low," Dr. Montalban noted. Baseline disease characteristics across the three treatment groups were similar for mean time since first MS symptoms, mean Expanded Disability Status Scale (EDSS), gadolinium contrast enhancing (Gd+) lesions, and mean number of relapses in the previous 2 years. The great majority in each group (>90%) were diagnosed as relapsing-remitting MS (RRMS). Dr. Montalban noted that the low-dose daclizumab group had a higher mean number of Gd+ lesions at baseline (1.1 vs 2.7 vs 0.8). The primary efficacy endpoint was total number of new or enlarged Gd+ lesions on monthly brain MRIs collected from weeks 8 to 24. The secondary efficacy endpoints were relapse rate from week 8 to week 24, and safety. For the intention-to-treat (ITT) population, the primary efficacy analysis shows a significant 72% reduction in mean number of new or enlarged Gd+ lesions in the high-dose daclizumab group ([P =.004). Low-dose daclizumab showed a 25% reduction, although this was not a significant difference (P =.501). "These positive effects were already evident, very early after just 4 weeks after the initiation of the trial," Dr. Montalban stressed.

Both the low- and high-dose daclizumab groups also achieved reductions in annualized relapse rates compared with placebo, although, these did not reach statistical significance (35%, P =.266; 33%, P =.317).

Safety analysis shows a similar incidence of overall infection rates across treatment groups (52% vs 51% vs 47%), although there was higher incidence of cutaneous adverse effects in the daclizumab treatment groups (27% vs 37% vs 31%). Conversely, there was a high incidence of injection-site reactions with placebo (24.7% vs 16.7% vs 18.7%). There were no deaths or opportunistic infections.

Dr. Montalban noted that there were higher rates of serious adverse events related to daclizumab treatment (2.6% vs 6.4% vs 6.7%); most of these were grade 3/4 serious infections (0% vs 2.6% vs 6.7%).

The higher dose of daclizumab in these patients who were nonresponders to their continuing IFNbeta therapy was associated with a significant reduction in Gd+ lesions that was accompanied by a favourable trend in reduction of relapse rates, Dr. Montalban stressed. "Daclizumab safety also supports moving forward into the next clinical studies," he added.

Funding for this study was provided by PDL BioPharma, Inc. and Biogen Idec Inc.


[Presentation title: Daclizumab in Patients With Active, Relapsing Multiple Sclerosis on Concurrent Interferon-Beta Therapy. Week 24 Data – Phase 2 (CHOICE) Study. Abstract 50]

Copyright © 2007 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content.

MN-166 (Ibudilast) Shows Efficacy in Relapsing Forms of Multiple Sclerosis: Presented at ECTRIMS

By Chris Berrie PRAGUE, CZECH REPUBLIC -- October 14, 2007 -- The anti-inflammatory and neuroprotective oral agent MN-166 (ibudilast) shows an excellent safety profile at 60 mg/day and provides significantly prolonged time-to-first relapse and attenuated brain volume shrinkage in patients with relapsing-remitting (RR) and/or secondary progressive (SP) multiple sclerosis (MS). Sponsor trial coordinator Richard E. Gammans, PhD, Chief Development Officer, MediciNova Inc., San Diego, California, presented the findings from a multicenter, randomised, double-blind, placebo-controlled, phase 2 study here on October 12 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). "Pharmacologically, MN-166 has mechanisms that include anti-inflammatory effects, such as phosphodiesterase inhibition, and neuroprotective effects, such as inhibition of [nitric oxide] synthesis and reduction in reactive oxygen species," he said. This study was thus designed to evaluate the effects of MN-166 in patients with MS. The study enrolled patients aged 18 to 55 years who were diagnosed with RRMS or SPMS using McDonald criteria, with continued relapses. They had one or more Gd-enhancing lesion on MRI scan taken 2 weeks before treatment start; and expanded disability status scale (EDSS) no greater than 5.5 at screening. The main exclusion criteria were based around no use of various immunosuppressants within 6 months, or of interferons -- corticosteroids and adrenocorticotropic hormone -- within 45 days of the initial magnetic resonance imaging (MRI) scan. The primary endpoint was cumulative active lesions on MRI. The secondary endpoints were clinical relapse and other MRI measures. Of 967 patients screened, 100 were randomized to placebo, 94 were randomized to 30 mg/day of MN-166, and 96 were randomized to 60 mg/day of MN-166 for the first 12 months of treatment, with clinical and MRI evaluations every 2 months. The 12-months extension phase was designed to evaluate the effects of continuation of MN-166 dosing, with placebo patients switched to MN-166 30 mg/day or 60 mg/day. Baseline clinical characteristics across these three treatment groups were similar for percent RRMS, percent spinal or cerebrum location of lesions, and number of relapses in previous 24 months. There were indications that time since both MS diagnosis and onset of symptoms were longer in the treated groups (39, 50, 60 months; 73, 96, 98 months; respectively). In terms of primary outcome of cumulative active lesions over the first 12 months, there was no significant difference amongst treatments. However, there was a modest difference between the highest dose of MN-166 and placebo, with an 18% reduction in cumulative active lesions, although this difference was not significant, indicated Dr. Gamman. Similarly, there were no significant differences between treatment group in the percent of patients with sustained disability progression on EDSS (8.0%, 5.3%, 4.1%). In contrast, for other MRI assessments over the 12 months, MN-166 at 60 mg/day showed not only a significant improvement in the percentage of brain volume reduction ([P =.035), but also a significant increase in the median time to first relapse (P =.04). Thus, the percentage of patients who were relapse-free at year 1 was significantly greater at the higher MN-166 dose (41% vs 41.5% vs 56.0% (P =.03).

Dr. Gammans said that MN-166 was very well tolerated, with 89% of patients completing the first 12 months of treatment. "The side effects were generally mild, and resolved without intervention, and there were no adverse observations on laboratory or [electrocardiographic] findings as well," he added.

When the two MN-166 treatment groups were combined, gastrointestinal side effects were the only adverse events to occur at 2-fold or greater times those of placebo (7.6% vs 14.7% vs 22.2%), although tolerance to these effects occurred rapidly (2-4 days). There were no deaths in the study.

Due to these modest effects of MN-166 on inflammatory lesion counts and based on its pharmacology, Dr. Gamman said that the clinical benefits of MN-166 60 mg/day arise primarily from its actions towards protection of neurons from damage, rather than towards reduction of inflammatory lesions.

At the same time, the excellent safety profile at 60 mg/day and the effects that reached significance in this study suggest that future studies with MN-166 should evaluate higher doses on disease progression and MRI measures of neuroprotection, rather than inflammation.

Funding for this study was provided by MediciNova Inc.


[Presentation title: Clinical Effect of the Neuroprotectant MN-166 in Relapsing Forms of MS. Abstract 52]

Copyright © 2007 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content.

Tolerogenic DNA Plasmid Vaccine Decreases Brain Lesions in MS Patients: Presented at ECTRIMS

By Chris Berrie PRAGUE, CZECH REPUBLIC -- October 13, 2007 -- Intramuscular injection of the tolerogenic DNA plasmid vaccine BHT-3009 that encodes full-length human myelin basic protein (MBP) is safe and well tolerated, and provides significant favourable benefit on several measures of brain lesion activity in patients with relapsing-remitting multiple sclerosis. This multicentre, randomised, double-blind, placebo-controlled phase 2b trial was presented here by coinvestigator Hideki Garren, MD, PhD, Vice President of Research, Bayhill Therapeutics, Palo Alto, United States, at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). During his presentation on October 12, Dr. Garren stressed the two important aspects of construction of BHT-3009 as a DNA plasmid. "We include the antigen, MBP, as the entire molecule, rather than specific epitopes, and we include some specific changes in the DNA background to try to drive the [T-cell] tolerance." In a previous 30-patient phase 1/2 trial, BHT-3009 was shown to be safe and well tolerated (Bar-Or et al., [Arch. Neurol. 2007, 64, 1407-1415).

The current study enrolled 289 patients who were aged 18 to 55 years and had a confirmed diagnosis of MS according to McDonald criteria, at least one relapse in the previous year, and not received any treatment with disease-modifying agents in the previous 6 months. Study subjects also had screening magnetic resonance imaging (MRI) scans that were consistent with MS, with 0-5 Gd-enhancing lesions and an expanded disability status scale (EDSS) of 3.5 or greater.

The aim of the study was to evaluate the efficacy and safety of BHT-3009 in patients with relapsing-remitting MS, and to confirm that BHT-3009 causes immune tolerance.

The primary endpoint was the rate of occurrence of new Gd-enhancing lesions on cranial MRIs performed every 4 weeks from weeks 28 to 48 of treatment. Secondary endpoints were cranial MRI measures of Gd lesion volume, T2 lesion volume/number, and T1 black hole volume. The researchers monitored for relapses and disability scores. Finally, the immune response to MBP was also determined, to confirm previous results and to prospectively identify patients who respond to BHT-3009.

Patients were randomised to one of three treatment arms: 96 received placebo; 104 patients received BHT-3009 0.5 mg (low dose); 89 patients received BHT-3009 1.5 mg (high dose). Treatment was administered by intramuscular injection on weeks 0, 2 and 4, and then every 4 weeks until week 44.

Patients' baseline disease characteristics, number of relapses in the previous year, mean EDSS and MS functional composite (MSFC) overall z scores. The three treatment groups also had similar baseline MRI parameters.

In the 267 patients in per protocol cohort evaluation from weeks 28 to 48, results show that low-dose BHT-3009 achieved a near-significant 50% decrease versus placebo in median 4-week rate of new Gd+ lesions per patient (P =.07). No high-dose BHT-3009 effects seen.

However, Dr. Garren stressed that while this primary endpoint was not satisfied, when the MRI results were taken over the full treatment period (weeks 8 to 48), the 61% reduction versus placebo at low-dose BHT-3009 was significant (P =.05).

At week 48, low-dose BHT-3009 achieved a significant 51% decrease in mean Gd+ lesion volume (P =.02), although there was only a trend for decrease in T2 lesion volume.

The immunology assessment was on the 80 patients in the subgroup with cerebrospinal fluid (CSF) samples at screening and at week 44. In the screening for CSF anti-MBP reactivity, the low-dose BHT-3009 patients with the higher antibody titers (with a 1:1 low:high cut-off) showed a significant decrease versus placebo in new Gd+ lesions per MRI at week 28 (P =.02). Similarly, for CSF auto-antibody changes from screening to week 48, there were 23 fewer myelin-specific auto-antibodies in the 0.5 mg BHT-3009 group, while the placebo group had no change in auto-antibodies.

In the safety analysis on the 286 patients who received at least one dose of BHT-3009, common adverse events were mostly mild to moderate, and relatively well balanced across treatment groups. Dr. Garren indicated that psychiatric adverse events were slightly higher in the placebo group (14.7% vs 8.7% vs 9.2%), and renal and urinary events were slightly higher in the 1.5 mg BHT-3009 group (5.3% vs 8.7% vs 11.5%). Adverse events that were severe or worse were also more common in the placebo group (11 vs 7 vs 8). However, these all differences were not statistically significant.

In terms of relapse and disability, there was an overall very low rate of MS relapse, with 0.4 relapses in the placebo group, with no significant differences across the groups for relapse rates, time to relapse, or in mean EDSS and MSFC in this trial, added Dr. Garren.

The higher 1.5 mg dose of BHT-3009 had no patient benefits, potentially due to induction of four proteolipid protein peptide (PLP) antibodies, he said. However, the 0.5 mg dose did provide significantly favourable benefit for several measures of brain lesion activity, he added.

At the same time, this latter treatment showed high levels of CSF auto-antibodies as predictive for best responders for this patient subgroup analysis, with BHT-3009 causing antigen-specific tolerance, as seen by the reduction in CSF auto-antibody levels.

Funding for this study was provided by Bayhill Therapeutics.


[Presentation title: Phase 2b Trial of a MBP-Encoding DNA Plasmid (BHT-3009) for the Treatment of Relapsing-Remitting Multiple Sclerosis (RRMS). Abstract 48]



Copyright © 2007 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content.

Study: Smoking Worsens Multiple Sclerosis

By Rafael B.

New research carried out at the Buffalo Neuroimaging Analysis Center (BNAC) of the University at Buffalo has shown that smoking increases the degree of disability of people who have the Multiple Sclerosis (MS) disease due to a increase of the degree of brain tissue shrinkage.

Results of this research were presented at the 23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis in Prague, Czech Republic.

The observed effect of smoking on brain shrinkage is based on the analysis of hundred of magnetic resonance images obtained from smoking and non smoking participants of a study aimed at investigating the risks that smoking has on this debilitating disease.

Robert Zivadinov, M.D., Ph.D., UB professor of neurology, director of the BNAC and first author on the study sais at the conference, "Cigarette smoke has many properties that are toxic to the central nervous system, and cigarette smoking has been linked to higher susceptibility and risk of progressive multiple sclerosis,"

According to Zivadinov, "No previous studies have investigated differences in MRI characteristics between MS cigarette smokers and MS nonsmokers,"

The study included 253 Multiple sclerosis patients who had relapsing-remitting MS -- acute attacks with full or partial recovery; 9 that experienced primary-progressive MS -- steady worsening from onset; and 90 that had secondary-progressive MS, characterized by occasional attacks and sustained progression. Another 16 participants had experienced their first Multiple Sclerosis onset.

Participant of the study were 35-55 years, and had been living with MS for 13 years (average). The average Expanded Disability Status Scale (EDSS) was 3.1. (EDSS is an average number derived from measures of various functions of the central nervous system based on scales ranging from 0 to 10---- The higher the number, the greater the disability-----).

Regarding smoking history 128 participants had smoked: 96 were active smokers who had smoked more than 10 cigarettes-per-day in the three months prior to the study start, and 32 were former smokers who had smoked cumulatively for at least 6 months sometime in the past. Two hundred and forty (240) participants were not active smokers.

Whe MRIs from smokers and nonsmokers were compared it was found that smokers had significantly higher disability scores and lower brain volume than the nonsmokers.

Also, it was observed that a significant relationship exists between a higher number of packs-per-day smoked and lower volume of the brain.

Zivadinov said, "MS patients should be counseled to stop smoking, or at least to cut down so they can preserve as much brain function as possible."

Source:

R. Zivadinov, M. Stosic, B.E. Teter, F.E. Munschauer, S. Hussein, J. Dufree, M.G. Dwyer, J.L. Cox, N. Hani, F. Nussenbaum, B. Weinstock-Guttman . Cigarette smoking and MRI characteristics in multiple sclerosis. Imaging 2 session. Saturday, October 13, 2007, 15:30 - 17:00. 23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis (ECTRIMS). Prague. Czech Republic. Abstract URL: http://registration.akm.ch/einsicht.php?

MSWorld Book Review

MS Toolkit: The Patients' & Caregivers' Guide to Multiple Sclerosis by Cary J Polevoy with Chris Bogard-Reynolds

Available for $20.48 at Amazon (see link below)

Reviewed by LizOP
MSWorld Book Reviewer


The authors did their homework and have written a well organized and candid journal of Polevoy's MS experience. Experiences anyone with MS can relate to. His wife, Chris Bogard-Reynolds, obviously worked well with him to round out all aspects of living with MS.

The second section is "What you need to know about MS." Whenever I see a long list of what can happen with MS, I am cautious to not become distressed because I know that only some symptoms relate to me. As with any book on what is possible with MS, I warn newly diagnosed people to read only what relates to them at the time, otherwise it is possible to become overwhelmed with unknown possibilities.

Polevoy discusses treatments and experimental treatments which always need to be discussed with our doctors before attempting.

The authors used an interesting format for the third section, "Issues in MS & Chronic Disease." They have a Q&A section, making it reader friendly.

The last part of the book is valuable information about "Social Security and Disability Insurance." It is thorough and covers a lot of territory where most readers can find their experiences included.

This book is a good resource from first-hand experience. The only real negative I see is the extremely small print size in the titles and the forms shown in the book. They are barely readable and I needed to refer to the table of contents.

Even so, this team put together a comprehensive book which is not an easy task, given they did this without a team of researchers and assistants, as in most MS resource books. For this I applaud them.

Check out their Website at www.ms-toolkit.blogspot.com.


Amazon.com will donate 5% of purchases made through the search link below to MSWorld®. For any purchases made through links to specific books from our individual book review pages, Amazon.com will donate 15%

Betaferon® treatment delays disability in early MS; strong efficacy not affected by neutralizing antibodies

Prague, October 12, 2007 – Betaferon® (interferon beta-1b) significantly delays the development of confirmed disability progression and the development of clinically definite multiple sclerosis (MS) in patients who are treated shortly after their first clinical MS event or “attack”. The presence of neutralizing antibodies (NAbs) does not affect the efficacy of early Betaferon® treatment.(1) This is according to new evidence from the landmark BENEFIT (BEtaferon in Newly Emerging multiple sclerosis For Initial Treatment) study presented today at the 23rd Congress of the European Committee for Treatment and Research in MS (ECTRIMS).

Neutralizing antibodies can develop in MS patients being treated with any of the currently available immunomodulatory therapies. However, there has been debate over whether or not such antibodies can affect a treatment’s efficacy.

“BENEFIT is a significant trial that provided the medical community with the first clear evidence on the value of treating patients with Betaferon® at the first clinical sign of MS to delay the accumulation of disability,” said Dr. Mark S. Freedman, Professor of Neurology at the University of Ottawa and investigator of the study. “The new data show that the presence of NAbs, regardless of the titre, does not reduce the efficacy of Betaferon® out to 3 years when administered after the first attack of MS. These results do not support the suggestion that the propensity for developing NAbs be a determining factor when making treatment decisions regarding Betaferon®.”

The study presented at ECTRIMS shows that:

• In patients starting treatment after a first MS attack, the efficacy of Betaferon® treatment in delaying the development of CDMS (Clinically Definite MS) and delaying confirmed disability was not affected by NAbs, regardless of NAb titre. Disability was measured using a validated, well-established scale called EDSS (Expanded Disability Status Scale) (2)

• Of 277 patients treated early with Betaferon®, 31.8 percent (88) were tested positive at least once for NAbs (≥1:20 NU/ml). 16.6 percent (46) of 277 patients had NAb titres ≥1:100 NU/ml, and 9 percent (25) had titres ≥1:400 NU/ml.

• 46.6 percent (41 of 88) of all patients with a documented NAb status reverted to NAb-negative status by Year 3. Among patients with higher NAb titres, 37 percent and 32 percent with NAb titres ≥1:100 NU/ml and ≥1:400 NU/ml, respectively, reverted to NAb-negative status by Year 3.

"The data from the BENEFIT study continue to provide the medical community with important insights that will help to optimize the treatment of patients in the earliest stages of MS. These results support previously published, peer-reviewed research showing that the NAb status does not affect the efficacy of Betaferon®," said Darlene Jody, M.D., Senior Vice President and President of Bayer HealthCare’s Specialized Therapeutics Global Business Unit.

Previously presented and published results of BENEFIT(3) demonstrated that over 3 years, patients treated with Betaferon® after the first MS attack had a 40 percent lower risk of developing confirmed disability and a 41 percent lower risk of developing clinically definite MS when compared to patients in whom treatment was delayed. No other MS therapy has demonstrated this effect in this early patient population.

Around the world, Betaferon® is approved for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations, as well as for use in patients after the first attack of MS.

About BENEFIT
BENEFIT is a multi-center trial conducted at 98 sites in 20 countries and included patients presenting with a first clinical episode suggestive of MS and typical MRI findings. The primary outcome measures are time to diagnosis of CDMS (Clinically Definite MS), time to confirmed EDSS (Expanded Disability Status Scale) progression and patient reported Quality of Life outcomes (FAMS-TOI). A total of 468 patients were randomized to receive either 250 micrograms of interferon beta-1b (Betaferon®) every other day or placebo as a subcutaneous injection in a double-blind fashion. The placebo-controlled treatment period lasted up to 24 months or up to the time when patients experienced a second attack and were diagnosed with clinically definite MS. All study participants were then invited to participate in a follow-up study with Betaferon® to prospectively assess the impact of such early versus delayed treatment with Betaferon® on the long-term course of the disease for a total observation time of five years. The three-year results are from a pre-planned analysis.

Previous published studies in this patient population have been criticized as less scientifically rigorous, because of their retrospective nature, unblinded assessments and the high number of patients lost to follow-up. The BENEFIT study was the first study in early MS patients designed to overcome these shortcomings.

About Betaferon® / Betaseron®
Betaferon®, which is marketed in the U.S. and Canada under the trademark Betaseron®, was the first disease-modifying drug introduced for MS and is a well-established treatment around the world. In the U.S., Europe and Japan, Betaferon® has been approved for all relapsing forms of MS. It is able to reduce the number of MS episodes by one-third, and the frequency of moderate to severe episodes by as much as 50 percent. Sixteen years’ follow-up of people treated with Betaferon® has shown that it is safe and well tolerated.

About Multiple Sclerosis
MS is a chronic, progressive disease of the central nervous system and the likelihood of disability increases the longer someone has MS. Symptoms of MS vary from person to person and can be unpredictable. They may include: Fatigue or tiredness, dimness of vision in one or both eyes, weakness of one or both legs, numbness and tingling in the face, arms, legs and trunk of the body, spasticity (muscle stiffness), dizziness, double vision, slurred speech and loss of bladder control.

References
(1) Freedman MS, Edan G, Hartung H-P, et al. Neutralising antibodies did not affect clinical outcomes after 3 years in the BENEFIT (BEtaferon in Newly Emerging multiple sclerosis For Initial Treatment) study. 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis, 2007
(2) Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444–52
(3) Kappos L et al. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 2007 Aug 4; 370(9585): 389-97

About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subsidiary of Bayer AG, is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Diabetes Care and Pharmaceuticals divisions. The pharmaceuticals business operates under the name Bayer Schering Pharma AG. Bayer HealthCare’s aim is to discover and manufacture products that will improve human and animal health worldwide. Find more information at www.bayerhealthcare.com.

About Bayer Schering Pharma
Bayer Schering Pharma is a worldwide leading specialty pharmaceutical company. Its research and business activities are focused on the following areas: Diagnostic Imaging, Hematology/Cardiology, Oncology, Primary Care, Specialized Therapeutics and Women's Healthcare. With innovative products, Bayer Schering Pharma aims for leading positions in specialized markets worldwide. Using new ideas, Bayer Schering Pharma aims to make a contribution to medical progress and strives to improve the quality of life. Find more information at www.bayerscheringpharma.de.

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.