Monday, January 26, 2009

Merck KGaA: Oral Investigational Treatment Cladribine Tablets for Multiple Sclerosis Significantly Reduced Relapse Rate in Phase III Pivotal Trial

• Two-year primary efficacy endpoint of CLARITY trial met: 58% relative
reduction in annualized relapse rate in the low total dose treatment group
and 55% in the high total dose treatment group

• Submission for registration of cladribine tablets planned for mid-2009

• Cladribine tablets are the first oral investigational multiple sclerosis
treatment to complete a two-year pivotal study

Darmstadt, Germany, January 23, 2009 – Merck KGaA and its Merck Serono division
announced today that the CLARITY1 Phase III pivotal trial of its proprietary oral
formulation of cladribine (cladribine tablets) met the two-year primary endpoint of
clinical relapse rate reduction in patients with relapsing-remitting multiple sclerosis

The two cladribine tablet treatment groups of the study, assessing different dose
regimens, demonstrated a statistically significant reduction in the annualized rate of
relapses compared to placebo. Patients from the lower total dose group experienced a
58% relative reduction in annualized relapse rates with respect to placebo (0.14 versus
0.33 for the placebo group; p<0.001). Patients from the higher total dose group
experienced a 55% relative reduction in annualized relapse rates with respect to
placebo (0.15 versus 0.33; p<0.001).

Overall, the frequencies of adverse events were low in the cladribine tablet treatment
groups and were comparable to that observed in the placebo group. Lymphopenia, an expected event based on the presumed mechanism of action of cladribine, occurred
more frequently in the cladribine tablet treatment groups. With the exception of
lymphopenia, the most frequently reported adverse events in the three study groups
were headaches and nasopharyngitis.

“We believe the CLARITY data mark an important milestone in the assessment of
investigational oral treatments for multiple sclerosis and that cladribine tablets have the potential to make a real difference in the lives of patients,” said Elmar Schnee, Executive Board Member with responsibility for the Pharmaceuticals business sector.

“Based on the successful completion of the CLARITY study, we plan to submit cladribine tablets for registration to the EMEA and to the FDA for mid-2009."

Secondary endpoints of the CLARITY study were also met, including reduction of lesion activity as measured by magnetic resonance imaging (MRI), proportion of subjects relapse-free and disability progression. Full study results will be submitted for
presentation at an upcoming scientific meeting.

The CLARITY study was a two-year (96 weeks), randomized, double-blind, placebo controlled, international trial. It enrolled 1,326 patients with relapsing-remitting MS
according to the revised McDonald criteria2. Study participants were randomized to one
of three different treatment groups consisting of two different dose regimens of
cladribine tablets or matching placebo tablets (1:1:1 ratio). Cladribine tablets were
given in two or four treatment courses in the first year, with each course consisting of once daily administration for four to five consecutive days, which means study patients took cladribine tablets for only 8 to 20 days during the year. In the second year, two treatment courses were administered to all patient groups. The primary endpoint of the CLARITY study was the qualifying relapse rate at 96 weeks. Secondary endpoints included MRI endpoints3, proportion of subjects relapse-free and disability progression at 96 weeks. Out of the 1,326 randomized patients, 90% of patients treated with cladribine tablets completed the study (92% in the lower total dose group and 89% in the higher total dose group) compared to 87% in the placebo group.

1 CLARITY: CLAdRIbine Tablets Treating MS OrallY

2 The McDonald criteria are diagnostic criteria for MS. In April 2001 an international panel in association with the National Multiple Sclerosis Society (NMSS) of America recommended revised diagnostic criteria for MS. They make use of advances in MRI imaging techniques and are intended to replace the Poser criteria. The new criteria facilitate the diagnosis of MS in patients who present with signs and symptoms
suggestive of the disease. The McDonald criteria for the diagnosis of multiple sclerosis were revised in 2005 to simplify and speed diagnosis, while maintaining adequate sensitivity and specificity.

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

About cladribine tablets

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

- The CLARITY (CLAdRIbine Tablets Treating MS OrallY) extension study: a two-year placebo-controlled extension of the CLARITY study, designed to provide data on the long-term safety and efficacy of extended administration of cladribine tablets for up to four years

- The ORACLE MS (ORAl CLadribine in Early MS) study: a two-year Phase III placebo-controlled trial designed to evaluate the efficacy and safety of cladribine tablets as a monotherapy in patients at risk of developing MS (patients who have experienced a first clinical event suggestive of MS). This trial was announced in September 2008.

- The ONWARD (Oral Cladribine Added ON To Rebif New Formulation in Patients With Active Relapsing Disease) study: a Phase II placebo-controlled trial designed primarily to evaluate the safety and tolerability of adding cladribine tablets treatment to patients with relapsing forms of MS, who have experienced breakthrough disease while on established interferon-beta therapy. This trial was announced in January 2007.

Cladribine tablets have been granted a fast track designation by the US Food and Drug Administration based on the need for an oral therapy in a subset of patients with relapsing forms of multiple sclerosis.

About Merck Serono and multiple sclerosis

Merck Serono is a leader in multiple sclerosis (MS) with Rebif® (interferon beta-1a), a disease-modifying drug used to treat relapsing forms of MS, which is registered in more than 80 countries worldwide. Full prescribing information for this product can be obtained by contacting the Company or visiting its website.

Additional therapeutic options are currently under development at Merck Serono, including cladribine tablets, currently in Phase III and potentially the first oral therapy for MS, as well as several products in early stage development. Merck Serono also is taking a leading role in developing an understanding of the role of genetics in MS.

About multiple sclerosis

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

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Merck is a global pharmaceutical and chemical company with total revenues of € 7.1 billion in 2007, a history that began in 1668, and a future shaped by 32,458 employees in 59 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

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Novartis launches Extavia®, a new therapeutic option to help patients combat devastating symptoms of multiple sclerosis

# Multiple sclerosis (MS) causes progressive disability and affects 2.5 million people worldwide including many young adults[1]

# Extavia offers patients and physicians a new branded version of standard-of-care interferon beta-1b

# Approved to treat MS patients from first signs of active disease to more advanced, relapsing forms

# Launch marks start of planned long-term partnership between Novartis and MS community

Basel, January 22, 2009 - Novartis has today announced the launch of Extavia®, a new version of the standard-of-care for relapsing forms of multiple sclerosis (MS), providing patients and physicians with an alternative option to help manage this devastating disease.

Extavia, a new branded version of interferon beta-1b, is available initially in Germany and Denmark with other European launches to follow during 2009. It is approved to treat a broad range of patients, from those with early signs of MS to those with more advanced relapsing forms of the disease.

"Extavia will provide patients and physicians with an additional option for receiving a mainstay of care in MS," said Trevor Mundel, MD, Global Head of Development at Novartis Pharma AG. "This important first step also opens the way for Novartis to build supportive partnerships with the MS community and lays the foundations for providing innovative approaches to MS care."

Extavia is the same medicinal product as Betaferon®*, an interferon beta-1b. This has a well characterised efficacy and safety profile with more than 700,000 patient-years' experience[2] and a 17-year track record of clinical use - the longest for any interferon beta in the treatment of MS[3].

MS is estimated to affect up to 2.5 million patients worldwide and is one of the leading causes of neurological disability in young adults1. The disease typically presents in relapsing forms involving acute self-limiting attacks of neurological dysfunction (or "relapses"), followed by complete or partial restoration of function.
Data have shown that interferon beta-1b produces a 34% reduction in annualized relapse rates (p<0.001), and patients are almost twice as likely to remain relapse-free for over two years compared to those on placebo (31% vs. 16%, p=0.007)[4]. Treatment with interferon beta-1b can also slow disease progression. After two years, nearly three-quarters of patients who had experienced a single episode of neurological disease lasting at least 24 hours did not progress to clinically definite MS[5].

The launch of Extavia in Europe by the Pharmaceuticals Division of Novartis marks the beginning of a long-term commitment to meet the therapeutic needs of the MS community. This will include the establishment of a support program for Extavia users that will foster cross-communication between patients and their physicians and nurses. In turn, this will lay the foundations for future potential innovations in MS therapy. The rollout of Extavia in key EU countries is expected during the coming months.

Novartis acquired the rights to its own branded version of interferon beta-1b in an agreement with Bayer Schering, the company that markets Betaferon. In backing Extavia, Novartis brings over 50 years of neuroscience expertise and resources to the MS community. This expertise has helped to pioneer early breakthrough treatments for a number of neurological and pathological conditions, some of which remain important therapies to this day.

MS is a chronic autoimmune disease of the central nervous system that causes inflammation and neurodegeneration. Pathology is characterised by the destruction of myelin, which helps neurons carry electrical signals in the brain[6]. The disease causes problems with muscle control and strength, vision, balance, sensation and mental function[6].

The beneficial effects of interferon beta are believed to be due to its modulation of the immune system to reduce inflammatory damage. Specifically, interferon beta limits the activation of immune cells that attack myelin, suppresses the production of inflammatory cytokines - a type of protein that amplifies the inflammatory response causing damage to myelin - and stimulates the production of anti-inflammatory cytokines.

Extavia has been filed with the US Food and Drug Administration for the treatment of relapsing forms of MS to reduce the frequency of clinical exacerbations (or relapses). Patients with MS in whom efficacy has been demonstrated include those who have experienced a first clinical episode and have features consistent with MS as shown by magnetic resonance imaging (MRI)[7].

Extavia is administered by subcutaneous (or under the skin) injection. Patients will have the choice of using either a fine (30 gauge) needle for manual injection or a convenient autoinjector.

* Betaferon® is a registered trademark of Bayer Schering Pharma AG.


The foregoing release contains forward-looking statements that can be identified by terminology such as "launches," "planned," "long-term," "can," "will," "likely," "commitment," "future," "potential," "expected," "estimated," "believed," or similar expressions, or by express or implied discussions regarding potential additional marketing approvals for Extavia, the roll-out of Extavia in potential additional markets, the potential development of additional MS therapies, or regarding potential future revenues from Extavia or additional MS therapies. Such forward-looking statements reflect the current views of the Company regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that will be approved for sale in any additional markets. Nor can there be any guarantee that Extavia will be launched in any additional markets. Neither can there be any guarantees that Novartis will successfully develop and bring to market any additional MS therapies. Nor can there be any guarantee that Extavia or such additional therapies will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Extavia and any such additional MS therapies could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; 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 healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, 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 97,000 full-time associates and operate in over 140 countries around the world. For more information, please visit


[1] World Health Organization. Neurology atlas, 2004. Accessed 16 Jan 2009.
[2] FDA approves Betaseron® for use after the first event suggestive of multiple sclerosis [press release]. Wayne, NJ: Berlex: 23 October 2006.
[3] Ebers G, Traboulsee A, Langdon D, Goodin D, Konieczny A. The interferon beta-1b 16-year long-term follow-up study: the results. Presented at the 16th meeting of the European Neurological Society; 27-31 May, 2006.
[4] The IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. Neurology. 1993;43:655-661.
[5] Kappos L, Freedman MS, Polman CH, 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;370:389-97.
[6] National Multiple Sclerosis Society website. Accessed January 12, 2009.
[7] Extavia proposed US Prescribing Information.

# # #

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Peptimmune Grants Major Pharmaceutical Company Exclusive Option to License PI-2301 for Multiple Sclerosis

Cambridge, Mass., January 15, 2009 — Peptimmune, Inc. (“Peptimmune”), a privately held biotechnology company, announced today that it has granted Novartis (NYSE: NVS) an exclusive option to obtain exclusive worldwide rights to develop and commercialize PI-2301, Peptimmune’s multiple sclerosis drug candidate. In a separate but related agreement, the MPM Bio IV NVS Strategic Fund L.P. made an equity investment in Peptimmune.In the event that Novartis exercises the option to PI-2301, Novartis would assume the global clinical development, manufacturing, and marketing of PI-2301 and all associated costs. Peptimmune would receive payments upon the option exercise and upon successful completion of certain development, regulatory, and commercial milestones. These payments together could total more than $500 million. In addition, Peptimmune shall be eligible to receive royalties on product sales. Additional terms were not disclosed.“We believe that Novartis represents an outstanding future partner for Peptimmune and the global development of PI-2301. This option agreement provides Peptimmune with access to both Novartis’ world class development expertise and the necessary capital to invest in this proprietary product,” said Thomas P. Mathers, President and CEO of Peptimmune.Todd Foley, Managing Director at MPM Capital commented, “Peptimmune and its world-leading expertise in peptide copolymers represent an attractive investment opportunity.”

About PI-2301PI-2301 is a peptide copolymer developed using Peptimmune’s novel platform peptide chemistry. PI-2301 is designed to enhance the regulatory response of the immune system, thereby controlling the pathogenic autoimmune response in certain diseases. PI-2301 is currently in Phase 1b development by Peptimmune.

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.

New Interferon Formulations Promise to Eliminate Injections in Multiple Sclerosis Treatment

SAN DIEGO, CA January 12, 2009/MarketWire/-- Nerveda Inc. and Aegis Therapeutics
LLC today announced preclinical results from their joint collaboration aimed at
developing non-injectable formulations of the beta-interferons. The beta interferons,
beta-1a (tradename Rebif®), and beta 1b (tradenames Betaseron® and Betaferon®) are
closely related injectable protein drugs in the interferon family that are used to treat both the relapsing-remitting and secondary-progressive forms of multiple sclerosis (MS). The beta interferons are currently administered by subcutaneous injection and have been proven clinically to slow the advance of multiple sclerosis and reduce the frequency of attacks. Current worldwide combined annual sales of Rebif®, Betaseron® and Betaferon® are approximately $4 Billion.

Because proteins are large and fragile molecules, they cannot be administered orally
and are typically administered by injection. They are often subject to instability due to aggregation of the protein molecules – particularly upon storage and handling at nonrefrigerated temperatures. The resulting protein aggregates are more poorly absorbed
into the blood stream upon injection due to their increased size, and induce development of circulating antibodies to interferon in patients that reduce the effectiveness of the drug over time.

Leading medical scientists at Johns Hopkins University, expert in the treatment of
neurological diseases, in collaboration with Nerveda and Aegis have applied Aegis’
Intravail® transmucosal absorption enhancement, and ProTek® protein stabilization
technologies to address these problems and have demonstrated for the first time that the beta interferons can be administered intranasally to prevent nerve damage in preclinical animal models of multiple sclerosis. In addition, the new formulations were shown to reduce or eliminate the immunogenicity of Betaseron® and Rebif®, administered either by injection or intranasally, while substantially increasing stability in a stress test involving constant agitation at elevated temperatures for extended periods of time.

Dr. Edward Maggio, Ph.D., CEO of Aegis Therapeutics, who participated in the
research, said, “since interferons will continue to be the foundation of MS therapy, it is critical that non-invasive delivery options for patients be developed.” Maggio also indicated, “the reduction in immunogenicity and the increase in stability also address a significant unmet need of the currently available beta-interferon therapies.”
Nerveda plans to begin testing the new formulation in clinical trials in early 2009 in
collaboration with clinicians and scientists at John Hopkins University Medical Center
and other sites.

* Rebif® is a registered trademark of Pfizer, Inc.
* Betaseron® is a registered trademark of Bayer Healthcare Pharmaceuticals
* Betaferon® is a registered trademark of Bayer Schering Pharma AG
* Intravail® and ProTek® are registered trademarks of Aegis Therapeutics, LLC

About Nerveda Inc.

Nerveda is a privately funded specialty pharmaceutical and diagnostic company focused
on improving the quality of life for patients suffering from neurodegenerative diseases
and their caregivers. Nerveda supports the clinical development of products licensed
from Johns Hopkins University, including neuroprotective compounds and stem cell
therapeutics that show promise in treating auto-immune disorders.

About Aegis Therapeutics

Aegis Therapeutics LLC is a drug delivery technology company commercializing its
patented or proprietary drug delivery and drug formulation technologies through productspecific licenses. Our patented Intravail® drug delivery technology enables the noninvasive delivery of a broad range of protein, peptide and non-peptide macromolecular therapeutics that can currently only be administered by injection. Aegis’ Intravail® absorption enhancement agents provide exceptionally high and unmatched bioavailability performance, comparable in efficiency to subcutaneous injection, via the intranasal administration route. Intravail® has also been successfully applied to buccal, oral, and rectal administration of small molecule, peptide, and nucleotide-analog type drugs. Our patented ProTek® technology allows creation of proprietary, easily manufacturable, and stable aqueous or lyophilized dosage forms that maintain the integrity and physiological activity of many protein and peptide therapeutics. ProTek® technology is applicable to injectable, intranasal, and other dosage forms of peptide or protein therapeutics.

For more information about Aegis, please visit the Aegis website at: htpp://

Aegis Therapeutics LLC
Ralph Barry, Chief Business Officer
1-858-618-1400 Ext. 102

Nerveda Inc.
Cam Gallagher, CEO
1-(858) 705-2365

Apitope and Merck Serono Announce Licensing Agreement on Novel Peptide Therapeutics for the Treatment of Multiple Sclerosis

Apitope and Merck Serono to collaborate on development and commercialization of ATX-MS-1467, Apitope’s peptide therapeutic for the treatment of multiple sclerosis (MS)

Bristol, England and Hasselt, Belgium, January 13, 2009 – Apitope Technology (Bristol) Ltd., a wholly owned subsidiary of Apitope International NV, announced today the signature of a research, development and commercialization agreement with Merck Serono, a division of Merck KGaA, Darmstadt, Germany. Under this agreement, Apitope has granted exclusive worldwide rights to Merck Serono to develop and commercialize Apitope’s product ATX-MS-1467. This peptide therapeutic has completed an initial clinical study in patients with MS. It is designed to induce immunological tolerance of the body’s T-cells to key autoantigens involved in the pathogenesis of MS.

ATX-MS-1467 is a novel peptide-based therapeutic derived from Apitope’s proprietary technology platform. Under the terms of the agreement, Apitope will receive an upfront payment and will initially be responsible for the further development of ATX-MS-1467, for which Merck Serono will fund the costs. Merck Serono will be responsible for all development activities from the beginning of Phase II clinical trials. Merck Serono will also provide committed funding to Apitope for research on other novel therapeutic peptides for the treatment of MS.

Under the terms of the agreement, Apitope is eligible to receive up to € 154 million in upfront, development and commercialization milestone payments, in addition to royalties on the net sales of products resulting from the collaboration.

“This partnership with Apitope strengthens our position as a leader in the field of innovative research and development in multiple sclerosis,” said Bernhard Kirschbaum, Executive Vice President Research and Development at Merck Serono. “ATX-MS-1467 represents a novel, targeted approach and may have the potential to complement existing MS drugs by offering a novel mode of action. By applying our existing stratified medicine approaches, we will also identify those MS patients who should benefit most from this potential treatment.”

“We are very pleased that ATX-MS-1467 has attracted a major pharmaceutical partner such as Merck Serono with extensive experience and leadership in the development of therapies for multiple sclerosis,” said Keith Martin, CEO of Apitope. “We view this collaboration as confirmation of Apitope's ability to develop early-stage first-in-class therapies for autoimmune diseases. In addition to continuing to build our in-house diagnostic platform in MS, we look forward to progressing ATX-MS-1467 with Merck Serono.”

ATX-MS-1467 consists of four short peptides that are derived from myelin basic protein, a key autoantigen in MS. It is specifically designed to target up to 70 % of MS patients who have a specific genetic profile.

About Apitope

Apitope International NV is a biopharmaceutical company with headquarters in Hasselt, Belgium, and a subsidiary in Bristol, England. The Company is developing novel products to revolutionize the diagnosis and treatment of chronic autoimmune and allergic disorders. Apitope’s therapeutic peptide technology platform is based on established scientific evidence showing that soluble, synthetic peptides can reinstate tolerance and selectively attenuate pathological immune responses. The ApitopesTM (Antigen Processing Independent epiTOPES) inhibit the immune system's harmful attack on the body while preserving normal immune responses to harmful antigens, such as infections. Apitope’s portfolio includes novel peptide therapies for MS as well as other autoimmune diseases and common allergies. Apitope is also developing novel diagnostic products for the early detection of autoimmune diseases such as MS and rheumatoid arthritis (RA). Apitope is backed by LRM; Vesalius Biocapital; Fast Forward, VINNOF; Hasselt University; The Wellcome Trust; the Daniels family, Wyvern Seedcorn Fund and the University of Bristol; Innovator Capital Limited advised on the recent funding rounds.

For more information, please go to

About multiple sclerosis

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

About Merck Serono and multiple sclerosis

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

About Merck Serono

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

Merck Serono has leading brands serving patients with cancer (Erbitux®), multiple sclerosis (Rebif®), infertility (Gonal-f®), endocrine and cardiometabolic disorders (Glucophage®, Concor®, Euthyrox®, Saizen®, Serostim®), as well as psoriasis (Raptiva®).

With an annual R&D expenditure of around € 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in autoimmune and inflammatory diseases.

About Merck

Merck is a global pharmaceutical and chemical company with total revenues of € 7.1 billion in 2007, a history that began in 1668, and a future shaped by 32,458 employees in 59 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

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Acorda expects to seek approval for drug

January 12, 2009

Acorda Therapeutics Inc., a Hawthorne-based biotech company, said that it is pushing ahead with plans to seek regulatory approval for its most promising product, Fampridine-SR, a drug to help people with multiple sclerosis walk.

The company said that it remains on schedule to file a new drug application for the medication with the U.S. Food and Drug Administration during the first quarter. It also expects to submit applications for the medication to regulators in Europe and Canada.

“We are also beginning discussions with potential marketing partners to explore commercialization options in Europe and the rest of world excluding the U.S.,” Chief Executive Officer Ron Cohen said in a written statement. “Achieving these milestones will bring us closer to our goal of making Fampridine-SR available to the many people with MS who may benefit from it.”

MS Relapse-Rate Higher in Adolescent-Onset Patients

By Michael Smith, North American Correspondent, MedPage Today
Published: January 12, 2009

Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

BOSTON, Jan. 12 -- When multiple sclerosis symptoms start in adolescence, the later annual relapse rate is nearly three times as great as it is for adult-onset disease, researchers here said.

The finding suggests that adolescent-onset MS has a more inflammatory disease course, according to Tanuja Chitnis, M.D., of Massachusetts General Hospital, and colleagues.

But the biological basis of the difference remains unclear and requires more study, Dr. Chitnis and colleagues said in the January issue of Archives of Neurology.

Several studies have shown that initial disease progression is slower in patients whose disease begins before the age of 18, the researchers said, but have differed on rates of relapse.

To clarify the issue -- and see whether the slower progression is related to relapse rates -- Dr. Chitnis and colleagues studied patients treated in the pediatric and adult MS centers at Massachusetts General and Brigham and Women's after July 2001.

Patients were eligible if treatment started within 12 months of the first symptom and were followed for at least a year. All told, the researchers identified 110 adult-onset patients and 21 whose disease started before they were 18.

The main outcome measure was annualized relapse rate, defined as the number of relapses divided by the number of person-years at risk. Rates for the adult and younger groups were compared using a proportional means model, as well as a negative binomial regression that excluded the first attack.

In both models, the researchers found that the annualized relapse rate was significantly higher in the younger cohort. Specifically:

* When the first attack was included, adolescent patients had an annualized rate of 1.4, compared with 0.65 for adult-onset patients. The difference was significant at P0.001 and yielded an adjusted rate ratio of 2.81 (with a 95% confidence interval from 2.07 to 3.81.

* Excluding the first attack yielded a pediatric rate of 1.13 and an adult rate of 0.4, also significantly different at P0.001.The adjusted rate ratio was 2.93 (with a 95% confidence interval from 1.93 to 4.46).

When the researchers controlled for the effects of disease-modifying treatment -- such as interferons, glatiramer acetate (Copaxone) or oral immunosuppressants -- the difference remained significant, with rate ratios of 2.82 and 3.02, depending on the model.

And when age was treated as a continuous variable, the age at onset was significantly associated with relapse rate at P0.001, Dr. Chitnis and colleagues found.

While several studies have shown that disease progression is slower in adolescent-onset cases, the researchers said they were unable to show that in this case because of the relatively short disease duration.

But if that is so, Dr. Chitnis and colleagues argued, the finding that younger patients have more relapses implies "greater plasticity, less neurodegeneration, and potentially more repair and remyelination in the younger nervous system."

The authors pointed out that "it remains possible that patients with more severe pediatric-onset MS were selectively evaluated at our centers. However, distance from the center, a proxy measure for referral bias, which has been shown to influence clinical characteristics in prior articles in the neurology and oncology literature, was not different between our pediatric-onset and adult-onset groups."

The study was supported by the National Multiple Sclerosis Society. The researchers did not report any conflicts.

Primary source: Archives of Neurology
Source reference:
Gorman MP, et al "Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis" Arch Neurol 2009; 66(1): 54-59.

UPDATE 1-Biogen moves long-acting Avonex to final trial-CEO

By Deena Beasley

LOS ANGELES, Jan 7 (Reuters) - Biogen Idec Inc (BIIB.O: Quote, Profile, Research) has moved a long-acting version of its multiple sclerosis drug, Avonex, directly into trials designed to meet requirements for regulatory approval, the company's chief executive said on Wednesday.

CEO Jim Mullen said during an investor conference held in New York that the company has completed Phase 1 trials and will study dosing the drug once every two weeks as well as once monthly.

"I think we've got a good chance of similar efficacy as interferons," he said.

Patients in the trials will be treated for one year with the injectable drug and full results will likely be available in two years, Mullen added.

Avonex, with sales of $573 million in the third quarter of 2008, is the leading drug for multiple sclerosis, an autoimmune disease in which the body mistakenly attacks the fatty myelin coating surrounding nerve cells.

Biogen, along with marketing partner Elan Corp Plc (ELN.I: Quote, Profile, Research), also sells MS drug Tysabri, which was taken off the market after its 2004 introduction when it was linked to a potentially fatal brain infection, but reintroduced beginning in 2006 because there were so few good options for patients with MS.

Mullen said investors continue to underestimate the newer drug's sales potential: "We have a much more bullish view on Tysabri than the Street does."

"We've got a 40 share of the overall MS market, which could easily go to 50," the CEO said.

He said other discrepancies between Biogen's outlook and that of Wall Street include the company's "more bullish view on the sustainability of Avonex," growth potential for the franchise surrounding non-Hodgkin's lymphoma drug Rituxan, and additional opportunities for trimming costs.

Mullen said Biogen will no longer report new cases of progressive multifocal leukoencephalopathy, the brain infection associated with Tysabri, through filings with securities regulators, but will instead issue weekly updates on its Web site. (Reporting by Deena Beasley; Editing by Andre Grenon and Matthew Lewis)

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Immune Molecule Decreases Severity Of Multiple Sclerosis-like Disease In Mice

ScienceDaily (Jan. 4, 2009) — A group led by Dr. Cedric Raine at Albert Einstein College of Medicine have explored the expression of an immune molecule (CXCL1) that interacts with myelin-producing cells, finding that CXCL1 decreases the severity of disease in a mouse model of multiple sclerosis (MS).

The autoimmune disease multiple sclerosis (MS) attacks the central nervous system, resulting in demyelination of neurons. Myelin-producing cells in the central nervous system are severely depleted in lesions in patients with MS.

Myelin-producing cells express immune receptors and have been shown to respond to the immune molecule CXCL1, although the role of CXCL1 in MS has not been previously explored. Dr. Raine and colleagues examined the effects of CXCL1 specifically expressed in the nervous system in a mouse model of MS. They observed decreased severity of disease and more prominent remyelination in these mice. CXCL1, therefore, may play a neuroprotective role in CNS autoimmune demyelination.

In future studies, Dr. Raine's group plans to determine how CXCL1 mediates protection in MS. "Exploration of these pathways affords novel therapeutic avenues to enhance the limited remyelination typically seen in MS."

Journal reference:

1. Omari KM, Lutz SE, Santambrogio L, Lira SA, Raine CS. Neuroprotection and remyelination after autoimmune demyelination in mice that inducibly overexpress CXCL1. Am J Pathol, 2009, 174:164-176

Adapted from materials provided by American Journal of Pathology, via EurekAlert!, a service of AAAS.

American Journal of Pathology (2009, January 4). Immune Molecule Decreases Severity Of Multiple Sclerosis-like Disease In Mice. ScienceDaily. Retrieved January 26, 2009, from­ /releases/2008/12/081230074742.htm