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
(MS).

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.

Disclaimer

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 http://www.novartis.com.

References

[1] World Health Organization. Neurology atlas, 2004. Accessed 16 Jan 2009. http://www.who.int/mental_health/neurology/neurogy_atlas_review_references.pdf
[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. http://www.nationalmssociety.org/about-multiple-sclerosis/symptoms/index.aspx. 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://www.aegisthera.com.

Contact:
Aegis Therapeutics LLC
Ralph Barry, Chief Business Officer
1-858-618-1400 Ext. 102
Email: rbarry@aegisthera.com

Contact:
Nerveda Inc.
Cam Gallagher, CEO
1-(858) 705-2365
Email: CGallagher@NervedaBio.com

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 www.apitope.com

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.

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

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)

© Thomson Reuters 2008. All rights reserved. Users may download and print extracts of content from this website for their own personal and non-commercial use only. Republication or redistribution of Thomson Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Thomson Reuters. Thomson Reuters and its logo are registered trademarks or trademarks of the Thomson Reuters group of companies around the world.

Thomson Reuters journalists are subject to an Editorial Handbook which requires fair presentation and disclosure of relevant interests.

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.

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

First Phase III results for FTY720, a novel oral therapy for MS, show superior efficacy compared to interferon beta-1a

* FTY720 significantly reduced annualized relapse rates by 52% (0.5 mg dose) and 38% (1.25 mg) vs. interferon beta-1a in one-year TRANSFORMS study[1]

* FTY720 generally well-tolerated and safety profile in line with previous experience[1]

* Regulatory submissions for FTY720 in US and EU on track for end of 2009; FREEDOMS and FREEDOMS II placebo-controlled Phase III studies continuing

* Multiple sclerosis, a devastating disease causing progressive disability, affects up to 2.5 million people worldwide including many young adults[2]

Basel, December 12, 2008 - Initial results from the one-year Phase III TRANSFORMS study show the investigational oral compound FTY720 (fingolimod) has superior efficacy to a current standard of care for patients with relapsing-remitting multiple sclerosis (MS). Patients on oral FTY720 experienced significantly fewer relapses than those treated with the injectable medicine interferon beta-1a (Avonex®*)[1].

The study, the first one-year head-to-head Phase III trial against a standard of care in MS, met its primary endpoint for both doses of FTY720.

The annualized relapse rate at one year for patients given FTY720 0.5 mg was 0.16, representing a 52% reduction compared to a relapse rate of 0.33 for interferon beta-1a (p<0.001). The FTY720 1.25 mg dose also showed a significant reduction in relapses with a rate of 0.20 representing a 38% reduction against interferon beta-1a (p<0.001). No statistically significant difference was seen between the two FTY720 doses[1].
Comprehensive analyses of the TRANSFORMS study data are ongoing, and detailed results are planned to be presented at a leading scientific congress in 2009. Regulatory submissions remain on track to be completed in the US and EU at the end of 2009.
"We are encouraged by the early results from TRANSFORMS, which represent a major step towards delivering an effective oral treatment for people with relapsing-remitting MS," said Trevor Mundel, MD, Global Head of Development at Novartis Pharma AG. "These positive results reinforce the potential for FTY720 to provide a significant advance in the future treatment of this devastating disease."

MS is a chronic autoimmune neurodegenerative disease of the central nervous system associated with irreversible progression of disability[3]. As many as 2.5 million people worldwide are affected by the condition[2] that typically begins in early adulthood between the ages of 20 and 40 years when patients are in the prime of life[4].

TRANSFORMS (TRial Assessing injectable interferoN vS FTY720 Oral in RrMS) is the first of three studies to report results in one of the largest Phase III clinical programs ever conducted in MS, involving more than 3,400 patients around the world.
As a head-to-head trial against interferon beta-1a, TRANSFORMS was designed to assess the efficacy of FTY720 compared to an established disease-modifying therapy in reducing relapse rates in patients with relapsing-remitting MS, the most common form of the disease. Two other studies - FREEDOMS and FREEDOMS II - are two-year placebo-controlled Phase III studies to assess the impact of FTY720 in reducing the frequency of relapses and slowing the progression of disability, and to further characterize the benefit-risk profile. Data from these studies to support regulatory submissions are expected in 2009.

TRANSFORMS was a one-year worldwide double-blind, double-dummy study that enrolled 1,292 patients. The study had three arms: oral FTY720 0.5 mg and 1.25 mg once-daily, and the active comparator interferon beta-1a given once-weekly by intra-muscular injection. The patient population in TRANSFORMS was consistent with the demographics and disease state seen in Phase III clinical trials for other disease-modifying treatments for relapsing-remitting MS[5].

The safety profile of FTY720 seen in TRANSFORMS was in line with previous clinical experience. The compound was generally well-tolerated with 87% of FTY720-treated patients completing the study on treatment. The proportion of patients discontinuing therapy was 10% in the FTY720 0.5 mg group, 15% in the FTY720 1.25 mg group, and 12% in the interferon beta-1a group[1].

The most commonly reported adverse events, seen in more than 10% of patients in all three study arms, were headache, nasopharyngitis and fatigue. Influenza-like symptoms were reported in 37% of patients treated with interferon beta-1a and in 4% of patients treated with FTY720[1].

Adverse effects seen in FTY720-treated patients included transient reductions in heart rate at the start of treatment, minor increases in blood pressure, and elevations in liver enzymes (also seen with interferon beta-1a). Macular edema (swelling of the center of the retina) was detected in less than 1% of FTY720-treated patients[1]. Seven cases of localized skin cancer were diagnosed in FTY720-treated patients (four basal cell carcinoma and three melanoma), while one case of squamous cell carcinoma was seen in the interferon beta-1a group. All of these localized skin lesions were successfully removed[1].

As previously reported, two fatal herpes infections occurred in patients treated with FTY720 1.25 mg. Both cases involved confounding factors impacting the outcome, but a role for FTY720 could not be excluded given its immunosuppressive effect.

In general, the safety profile of the FTY720 0.5 mg dose appeared to be better than that of the 1.25 mg dose, including lower rates of infections and bradycardia. Further analyses of the TRANSFORMS data and results from the ongoing Phase III studies will help to provide a more comprehensive assessment of FTY720's benefit-risk profile.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "on track," "planned," "encouraged," "potential," "to assess," "to further characterize," "expected," "appeared to be," "will," or similar expressions, or by express or implied discussions regarding potential regulatory submissions or marketing approvals for FTY720 or regarding potential future revenues from FTY720. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with FTY720 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that FTY720 will be submitted for approval in any market by the end of 2009 or at any time. Nor can there be any guarantee that FTY720 will ever be approved for sale in any market. Neither can there be any guarantee that FTY720 will achieve any particular levels of revenue in the future. In particular, management's expectations regarding FTY720 could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data (including the upcoming results of the FREEDOMS and FREEDOMS II trials) and unexpected additional analysis of existing clinical data (including the results of the ongoing additional analyses of the TRANSFORMS clinical data); unexpected regulatory actions or delays or government regulation generally; competition in general; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, 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 http://www.novartis.com.

References

[1.] Novartis. Data on file.
[2.] World Health Organization. Neurology atlas, 2004. http://www.who.int/mental_health/neurology/neurogy_atlas_review_references.pdf (Accessed 30 November 2008).
[3.] Confavreux C, Vukusic S. Accumulation of irreversible disability in multiple sclerosis: from epidemiology to treatment. Clin Neurol Neurosurg 2006;108:327-32.
[4.] Confavreux C, Aimard G, Devic M. Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients. Brain 1980;103:281-300.
[5.] Cohen J, et al. Oral fingolimod (FTY720) versus interferon beta-1a in relapsing-remitting multiple sclerosis: baseline patient demographics and disease characteristics from a Phase III trial (TRANSFORMS). Abstract at WCTRIMS, April 2008.
[*] Avonex® is a registered trademark of Biogen Idec.

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Elan seeks deals to raise cash

Tue Nov 18, 2008 6:11pm EST

NEW YORK (Reuters) - Elan Corp Plc (ELN.N: Quote, Profile, Research, Stock Buzz)(ELN.I: Quote, Profile, Research, Stock Buzz) aims to cut costs, close locations and raise up to $500 million as it seeks to strengthen its balance sheet and offset slower growth of its multiple sclerosis drug Tysabri.

Elan, which expects to generate revenue of about $1 billion in 2008, is based in Ireland, but also has facilities in San Francisco, New York, Boston, Pennsylvania, Georgia and Tokyo.

Chief Executive Officer Kelly Martin said on Tuesday at the Reuters Health Summit in New York, that Elan is considering closing two of those locations or reducing its presence there, though the company has not yet decided which ones.

"We are currently going through a process where we are evaluating where we can take costs down and reallocate and reduce," he said. "There are a couple of locations we can potentially exit entirely."

In the nine months ended September 2008, Elan posted a net loss of $240.5 million. It is burning cash at a rate of more than $300 million a year, and it has $1.7 billion in debt that comes due over the next five years.

Elan's U.S. stock has fallen over 80 percent since early July to $6.06 late Tuesday afternoon, hurt by safety concerns over Tysabri and disappointing results from a mid-stage trial of its experimental Alzheimer's disease vaccine.

The company is on track to run out of money in less than two years if it doesn't take firm action.

To that end, Martin said he wants to raise between $300 million and $500 million within the next six to eight months, and he expects to do that by selling the rights to some of its experimental products.

Elan recently tried to sell its drug technology business, worth about $1 billion, but the credit crisis killed off a hoped-for sale to private equity and a sale is now unlikely for at least a year, Martin said.

"I'm not optimistic the markets will get back to normalcy any time soon," he said. "Our plans are not to wait around for a transaction but to run the business."

Kelly said the business is profitable but is not central to its portfolio of neurology drugs, and the company still hopes to sell it once the market improves.

For now, the company will focus on raising money by selling rights to experimental drugs in areas such as cancer and rheumatoid arthritis, products that are in early stages of development.

"By the middle of 2009 you can expect us to do something with our pipeline," he said.

Martin said the company is determined to keep its pipeline of drugs for neurological disorders, including experimental products to treat Alzheimer's disease, Parkinson's disease and Parkinson's disease.

Elan and its U.S. partner Biogen Idec Inc (BIIB.O: Quote, Profile, Research, Stock Buzz) have said they expect 100,000 patients to be taking Tysabri by the end of 2010, a figure Kelly said would represent around 20 percent of the market, but some analysts consider that over-optimistic.

Martin said it will begin to become clear over the next few quarters whether the companies can reach that figure, as they will reflect physician responses to the latest cases of PML, a potentially deadly brain infection that caused the drug to be temporarily withdrawn in 2005.

In the third quarter, Biogen said sales of Tysabri had slowed, though it maintained it can still meet the patient target of 100,000. For that to happen, growth will have to accelerate.

Tysabri was reintroduced in 2006, with stricter warnings, and physicians had started to become more comfortable with the drug. Then, at the end of July, two more cases of PML were reported. And another was reported in October.

That has once again cast doubt on the ultimate sales potential for the drug, but Martin sounded optimistic.

"We are hoping the emotion and rumoring around PML is beginning to fade away a little bit," he said. "I think a 20 percent market share for the drug is a very achievable number over time."

(For summit blog: summitnotebook.reuters.com/))

(Reporting by Toni Clarke, Ben Hirschler; Editing by Richard Chang)

© Thomson Reuters 2008. All rights reserved. Users may download and print extracts of content from this website for their own personal and non-commercial use only. Republication or redistribution of Thomson Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Thomson Reuters. Thomson Reuters and its logo are registered trademarks or trademarks of the Thomson Reuters group of companies around the world.

MS services are poor

Greg Baxter

greg.baxter@imt.ie

Ireland has scored poorly, relative to the rest of Europe, on care for multiple sclerosis from the EU body Multiple Sclerosis — the Information Dividend (MS-ID).

According to the Dividend’s MS Barometer 2008, which compares MS services around Europe, Ireland scored 24th out of 32 countries, just behind Croatia and ahead of Spain. Germany scored the best, and Romania finished last.

The countries were measured on access to treatments and therapies; MS research agenda; employment of people with MS; empowerment of people with MS; reimbursement of MS costs; accurate MS data collection; and MS medication coming to the market.

Ireland scored particularly poorly on empowerment of people with MS, scoring zero out of a possible 45 points. Romania also scored zero.

A country’s empowerment scores take into account the presence of a consultation group on MS that advises Government on MS policies; whether that MS society is a member of the body that decides on the reimbursement of a new MS therapy; whether the MS society has consultative status with your national administration; whether a self-management course exists for people with MS to empower them to co-manage their own health as far as possible; and other services.

Ireland also scored zero points in the area of data collection. Fourteen countries registered a score in this area, but 18 scored zero.

In all categories but reimbursement of costs related to MS, Ireland scored below average.

Environment Causes Increase In Multiple Sclerosis Among Women Only

17 Nov 2008

Gender has become a dominant factor in Multiple Sclerosis (MS) during the last decades. Already with a ratio of 3.2 to 1 MS is gradually changing into a disease predominantly among women. Since genetic factors can be ruled out as a cause of this gender related increase, scientific attention is on environmental factors that may increase MS risk in women exclusively. Most likely environmental factors include smoking, viral infections, Vitamin D deficiency, hygiene changes and dietary factors.

Almost 400 MS scientists and clinicians from around the world gathered this week during a medical scientific conference on 'Multiple Sclerosis and Gender', organized by the independent European Charcot Foundation, to share and discuss their scientific views on the backgrounds of this major shift in gender ratio.

"In due course the raised attention on gender related topics will undoubtedly lead to better results and questions regarding individualized MS treatment, both in women and men", professor O.R. Hommes, chairman of the European Charcot Foundation stated. "This conference has raised the simple question whether females with MS should be treated differently than males".

One of the main focal points in the gender related approach is the effect of pregnancy on disease progression in MS. The disease practically disappears during the last trimester of pregnancy. Why is that and can we use our vast knowledge of natural female sex hormones, such as estriol, progesterone and prolactin, to develop new ways of treating women with MS? Several phase III clinical trials are already underway that will provide answers to this question by the end of 2009.

Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system leading in time to severe disability. This chronic disease is affecting 70 to 200 per 100.000 persons in Europe.

European Charcot Foundation

Article URL: http://www.medicalnewstoday.com/articles/129672.php

Multiple Sclerosis Progression Can Be Predicted With MRI

ScienceDaily (Nov. 6, 2008) — A new study published in Journal of Neuroimaging shows that MRI scans used on multiple sclerosis (MS) patients to determine if the disease has affected gray matter in the brain can identify those at-risk for progression of disability.

MS affects approximately 400,000 people in the United States and as many as 2.5 million worldwide. It is the most common cause of progressive disability in young adults. While the cause of the disease remains unknown, it is characterized by damage to the covering over the nerve fibers in the brain and spinal cord, or to the nerve fiber itself.

In an attempt to understand the causes of disease progression, researchers at the Partners MS Center, led by Dr. Rohit Bakshi and his team, have developed new ways to detect gray matter damage.

Dr. Bakshi, Director of the Laboratory for Neuroimaging Research and an Associate Professor of Neurology and Radiology at the Brigham and Women's Hospital and Harvard Medical School, led a four year follow-up study, which found that patients with unnatural darkness of gray matter structures as seen on MRI pictures carried a higher risk for progression of physical disability. This abnormal darkness is referred to as T2 hypointensity, and is suggestive of excessive iron deposits. In addition, the researchers found that the new marker of gray matter damage showed closer correlations with patients' clinical status than other established MRI markers of disease severity, including lesions, also known as "plaques," and shrinkage of the brain, also know as "atrophy."

"MRI scans obtained from patients with MS are being used to develop measures and techniques that can accurately measure the visible and hidden damage to the brain, especially in gray matter areas and can more accurately predict the course of the disease," says Bakshi.

As a result of the findings, MRI-based measurement of gray matter damage may be used as a surrogate marker of disease progression. Physicians may therefore be able to more accurately identify patients at risk for developing this progressive disease.

MS has been traditionally viewed as a disease affecting the white matter of the brain, where messages are transferred between the brains gray matter sections, which control the processing of information. While prior research has shown that the brain's gray matter is also affected, studies detailing its effects have been limited. In addition, current therapies for MS are incomplete, raising the need to better understand disease mechanisms and the biomarkers of disease progression. If excessive iron in gray matter contributes to damage, this would open a new avenue for developing better therapies.

Journal reference:

1. Neema et al. Deep Gray Matter Involvement on Brain MRI Scans Is Associated with Clinical Progression in Multiple Sclerosis. Journal of Neuroimaging, 2008; DOI: 10.1111/j.1552-6569.2008.00296.x

Adapted from materials provided by Wiley-Blackwell, via EurekAlert!, a service of AAAS.
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA

MLA
Wiley-Blackwell (2008, November 6). Multiple Sclerosis Progression Can Be Predicted With MRI. ScienceDaily. Retrieved November 10, 2008, from http://www.sciencedaily.com­ /releases/2008/11/081105164308.htm

Avigen Announces Restructuring and Strategic Direction

ALAMEDA, Calif., Nov 3, 2008 (GlobeNewswire via COMTEX News Network) -- Avigen, Inc. (Nasdaq:AVGN), a biopharmaceutical company innovating therapeutics for neurological care, today announced a significant restructuring of the company aimed at preserving cash and reassessing its strategic opportunities. As a result of the restructuring, which will involve staff reductions of over 70 percent of the company's total workforce, Avigen expects to have sufficient cash to fund operations for over four years.

"Our deepest gratitude goes out to all the talented and dedicated employees who have worked so hard to complete a timely and well executed AV650 clinical program, as well as enhance the value of our other clinical-stage drug candidates from our internal research and development," said Kenneth Chahine, Ph.D., J.D., Avigen's President and Chief Executive Officer. "By reducing to only a core team, however, we can significantly lower our infrastructure costs, while retaining the know-how and expertise necessary to monetize our current assets and identify opportunities to acquire new assets. We believe our strong cash position and management team will make Avigen an attractive partner in this challenging financial climate."

Highlights:


-- Avigen expects to end 2008 with top-line cash and securities of
approximately $49 million and believes this restructuring
will extend its resources to support at least four years of
operations, including providing funds to develop one asset to a
meaningful value inflection point without additional equity
financings.

-- Avigen's contract with Sanochemia Pharmaceutica AG regarding
AV650 has been terminated to avoid further payment obligations
on the part of Avigen.

-- Avigen believes the breadth and value of AV411 can be best
realized with the support of a partner; therefore, Avigen
intends to seek a partner and does not currently plan to
initiate the Phase 2b development program for neuropathic
pain. Current and future National Institute on Drug Abuse-funded
Phase 2a trials in opioid withdrawal and methamphetamine relapse
will continue.

-- Proceeds from the sale or partnering of Avigen's current assets
(AV411 and AV513) could significantly increase its cash position
and its ability to develop additional assets to meaningful value
inflection points without additional equity financings.


"Our experienced team has faced similar challenges, and has demonstrated the ability to take decisive action to create valuable opportunities," said Dr. Chahine. "Given the current economic environment, we believe this strategy represents a sound plan that will not only withstand, but capitalize on, the current market conditions."

About AV411

AV411 is a first-in-class orally bioavailable small molecule, a glial attenuator that suppresses pro-inflammatory cytokines IL-1 beta, TNF alpha, and IL-6, and may upregulate the anti-inflammatory cytokine IL-10. While considered a New Molecular Entity (NME) in the United States and Europe, the drug was first approved in Japan more than 15 years ago. The drug has been prescribed to over one million patients for a different indication and has a good post-marketing safety profile in nearly 15,000 patients studied at the prescribed doses.

Glial activation in the brain and spinal cord contribute to the establishment and amplification of the chronic pain state. As part of its program investigating glial attenuation as a novel approach to the treatment of neuropathic pain, Avigen discovered that AV411 (ibudilast) was efficacious in standard preclinical models of opioid withdrawal. While ibudilast was initially developed as a non-selective phosphodiesterase (PDE) inhibitor for the treatment of bronchial asthma, its efficacy in neuropathic pain models appears to be independent of this activity. AV411 has advanced through Phase 1 and 2a clinical trials for neuropathic pain and is currently in a NIDA-funded trial with Columbia University addiction research specialists for opioid withdrawal. Additional preclinical research has revealed that AV411 can attenuate opioid-induced glial activation and both behavioral and neurochemical markers of opioid-induced reward and withdrawal. Moreover, collaborative studies with NIDA have revealed utility in methamphetamine relapse in animals which is being translated to a NIDA-funded exploratory clinical trial with UCLA investigators in 2009. Based on its research, Avigen has filed for patents protecting the use of AV411, as well as for patents on AV411 analogs which the company believes have the potential to be effective second generation molecules. Additional information on AV411 can be found on Avigen's website at www.avigen.com.

About Avigen

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

The Avigen, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=2981

Statement under the Private Securities Litigation Reform Act

This press release contains forward-looking statements, which include, among others, statements relating to Avigen's expectations that the current restructuring and staff reduction will reduce its infrastructure costs and extend its financial resources to support at least four years of operations without additional equity financings; that it will retain the know-how and expertise necessary to monetize its current assets; that it will be able to identify and acquire new assets; that it will be able to secure a partner to initiate the AV411 Phase 2b development program for neuropathic pain; that current and future National Institute on Drug Abuse-funded trials in opioid withdrawal or methamphetamine relapse will continue; that Avigen can avoid further payment obligations to Sanochemia beyond those already paid; that it will be able to take any asset to a meaningful value inflection point with or without additional equity financings; that it can generate any proceeds from the sale or partnering of current assets; and that the Company's current strategy will allow it to withstand or capitalize on the current market conditions. These risks and uncertainties include: unexpected expenses incurred with respect to the restructuring may occur; savings from the restructuring may not be as much as Avigen expects due to unexpected impediments to reducing expenses; in this economic environment, Avigen may not be able to find a partner for AV411 on terms favorable to Avigen; that costs necessary to bring products to a meaningful inflection point may be more than Avigen expects; and those detailed in reports filed by Avigen with the Securities and Exchange Commission, including Avigen's quarterly report on Form 10-Q for the period ended June 30, 2008, under the caption "Risks Related to Our Business" in Item 2 of Part I of that report, which was filed with the SEC on August 11, 2008.

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

SOURCE: Avigen, Inc.

Avigen, Inc.
Michael Coffee, Chief Business Officer
510-748-7372
IR@avigen.com
1301 Harbor Bay Parkway
Alameda, CA 94502

Source MDx, Brigham and Women's Partner on Multiple Sclerosis Biomarker Discovery

[November 3, 2008]

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) - Source MDx has formed a partnership with Boston’s Brigham and Women’s Hospital to study RNA-based biomarkers for multiple sclerosis, the company announced today.

The duo plans to use expression profiling to find diagnostic markers, markers for active or stable MS, and response markers for currently available MS therapies.

Multiple sclerosis, a chronic central nervous system inflammatory disease, has unpredictable and highly variable progression. For instance, many individuals with the disease experience partial or complete remission punctuated by MS relapses whereas others experience progressively worse symptoms. Current methods for determining the stage of disease are imprecise, but some research suggests that gene expression profiles could help map disease progression and guide treatment, the companies said.

“Our objective is to evaluate RNA-based markers in the broader context of each patient’s genetics, protein markers, family history, and clinical information in order to determine markers that can help in making a diagnosis of MS and prognosticate on drug response in MS,” Brigham and Women’s Hospital neurology researcher Phil De Jager, co-leader of the study, said in a statement. “By doing so, we hope to be better able to identify makers that could lead to improved diagnostic tools, therapies, or treatment regimen.”

The research ties into ongoing work by De Jager and Brigham and Women’s molecular immunologist David Hafler and others in the International Multiple Sclerosis Genetics Consortium and Partners Healthcare MS Center.

Source MDx said that it has patented the use of gene expression data for identifying, monitoring, and treating MS. The company added that it has identified and patented MS gene expression biomarkers linked to MS in independent studies by De Jager and Hafler.

Virtual Reality Helps MS Patients Regain Stability While Walking

Medigait LLC announces the release of a new device that combines virtual reality programming and real-time motion detection into a cell-phone sized device that helps MS patients restore their ability to walk more normally. The neuroplastic brain response stimulated by this device helps MS patients jump-start the rewiring process inside the patient's brain. Their brain literally rewires itself creating new healthy walking circuits bypassing diseased areas sometimes in as little as two weeks.
When I saw these positive results I was amazed, very excited, and gratified.

Haifa, Israel (PRWEB) November 3, 2008 -- Studies performed over the last few years show many Multiple Sclerosis (MS) patients no longer have to live with a meandering or unsteady gait caused by their disease. According to a study published in the highly acclaimed medical journal "Neurology", closed-loop visual feedback helps MS patients improve their walking. Both stride length and walking speed improved dramatically helping MS patients walk safely.

Better yet, a study published in the "Journal of Neurological Sciences" found that when closed-loop auditory feedback was combined with visual cues, MS patients showed even more improvement and confidence while walking.

Based on concepts discovered while working on a NASA project helping helicopter pilots to safely navigate around tall objects, Professor Yoram Baram, CEO of Medigait LLC, created the GaitAid Virtual Walker. The Virtual Walker is a highly sophisticated device about the size of a cell phone paired with a set of high-tech eyeglasses. Professor Baram designed this device specifically to help patients with MS and other movement disorders regain their stability while walking.


GaitAid


GaitAid

Medigait announces the re-introduction of the GaitAid Virtual Walker to the market after locating a reliable high quality US-based medical device company to build the device for them.

The GaitAid Virtual Walker combines proven visual aids and audio feedback helping patients with MS and other movement disorders improve their stability while walking through a process called neuroplasticity. This process essentially rewires the patient's brain by creating new healthy circuits to bypass disease-damaged areas.

The National Multiple Sclerosis Society estimates there are approximately 400,000 people in the United States with MS. World-wide about 2.5 million people suffer from MS.

Because MS afflicts both the central and the peripheral nervous systems, not all MS patients show the same symptoms. However, a large percentage of MS patients exhibit loss of balance and muscle coordination affecting their ability to walk safely. Although a cure for MS hasn't been found, the GaitAid Virtual Walker offers a safe, effective, and non-pharmacological method of helping MS patients walk better leading to more productive and safer lives.

Clinical studies have shown major improvements to walking speed and stride length in 70% to 85% of MS and other movement disorder patients. Some patients have been helped to the point of no longer needing the device except occasionally to maintain their improvement.

Clinical studies appearing in medical journals, Neurology, Neural Processing Letters, and Journal of Neurological Sciences described the device as being effective but without the risk or possible adverse side effects caused by surgery and medication. Links to this information can be found at http://www.gaitaidmedical.net/studies.html

"When I saw these positive results I was amazed, very excited, and gratified." -- Professor Yoram Baram Phd.

"The results clearly indicate that the device helps patients with MS control their gait. The degree of improvement is proportional to the degree of impairment. The results support the potential role of the device as a rehabilitation modality in MS, and substantiate their specific implementation in efforts to alleviate, improve, and restore mobility in patients with gait disturbances due to neurological disorders in general." -- Ariel Miller, MD, Multiple Sclerosis Center, Carmel Medical Center and Rappaport Faculty of Medicine & Research Institute

For more information on the GaitAid Virtual Walker device:

Visit our website: http://www.medigait.com or
contact Amir Baram by calling 1-888-777-9906 (U.S) or email him at
support (at) medigait (dot) com

About MediGait LLC
MediGait was founded by Yoram Baram, who received his PhD degree from MIT and is presently a Professor of Computer Science and incumbent of the Roy Matas / Winnipeg Chair in Biomedical Engineering at the Technion, Israel Institute of Technology. The idea for this project was sparked 12 years ago while Professor Baram was designing a mechanism for NASA to navigate low-flying helicopters around obstacles. The concept of the design, which Baram later applied to the medical device, is that the optical images of objects help the observer navigate, stabilize and pace movement in space.

About the Technion Institute of Technology
The Technion-Israel Institute of Technology is Israel's leading science and technology university. Home to the winners of the Nobel Prize in science, it commands a worldwide reputation for its pioneering work in nanotechnology, electrical engineering, computer science, biotechnology, water-resource management, materials engineering, aerospace and medicine. The majority of the founders and managers of Israel's high-tech companies are alumni.

Interferon Could Be A Key To Preventing Or Treating Multiple Sclerosis

31 Oct 2008

Multiple sclerosis (MS) results when the body's own defense system attacks nerve fibers in the brain and spinal cord. Now scientists led by John Russell, Ph.D., at Washington University School of Medicine in St. Louis have shown that interferon-gamma plays a deciding role in whether immune cells attack and injure the central nervous system (brain and spinal cord) in mice.

Interferon-gamma is an immune system protein that helps the body defend itself from invaders. In their latest research, which appeared in the October issue of the Journal of Experimental Medicine, the researchers show that interferon-gamma determined whether activated immune cells previously primed to go after nerve cells would actually cause nerve damage in experimental mice.

The researchers found that in the cerebellums and brainstems of the mice, interferon-gamma was protective. However, in the spinal cord, interferon-gamma had the opposite effect, permitting nerve cell damage.

"Some studies show that the most serious cases of MS in people occur when the immune system specifically targets the cerebellum, a part of the brain responsible for sensory perception, coordination and movement control," says Russell, professor of developmental biology. "Our study suggests that researchers need to look at the amount of interferon-gamma produced in the cerebellum and other brain regions in people with MS."

The researchers studied mice genetically engineered to be physiologically "blind" to interferon-gamma the mice had none of the usual receptors on their cells that recognize and respond to interferon-gamma. So in these mice it was as though interferon-gamma didn't exist.

In the interferon-insensitive mice, immune cells primed to attack nerves and then injected into the mice's veins were able to get into the cerebellum and brain stem and initiate nerve cell damage leading to MS-like disease.

In comparison, in mice with normal interferon-gamma recognition, immune cells were prevented from entering the brain and causing problems. The exact mechanism to account for this is still under study.

"Down the road, we would like to investigate whether we can prevent disease in the cerebellum in mice if we promote interferon production in that brain region," Russell says. "One way to do that would be to use gene therapy to insert a gene that would increase interferon in the mice's brains. Then we would test the mice to see if they gained protection against MS-like disease."

In contrast to its protective role in the brain, in the spinal cord interferon-gamma helped instigate nerve damage. In mice with intact interferon-gamma recognition, activated and injected immune cells were able to enter the spinal cord and cause injury. In mice without interferon recognition, the immune cells were unable to initiate spinal cord inflammation, and no damage occurred.

"Our research shows that certain characteristics inherent in different regions of the brain and spinal cord can provoke immune attacks on nerve cells," Russell says. "An understanding of the mechanisms involved in immune system invasion of the nervous system may allow development of better models for determining prognosis and treating many neurological diseases such as multiple sclerosis."

This latest research bolsters Russell's central hypothesis about MS and related disorders, which goes against some widely held assumptions. He holds that in physiological circumstances that ultimately lead to MS, the central nervous system itself allows or even aids immune system attacks.

"A scientifically popular view of how MS occurs is that the immune system somehow gets armed against normal brain antigens and attacks neurons," Russell says. "In that view, brain cells have a passive role. But in this and previous research, we've shown that there's a 'conversation' between the immune system and the central nervous system and that molecular signals passed between them are involved in the development of MS-like disease in mice."

Lees JR, Golumbek PT, Sim J, Dorsey D, Russell JH. Regional CNS responses to IFN-γ determine lesion localization patterns during EAE pathogenesis. Journal of Experimental Medicine. 2008 Oct 27;205(11):2633-2642.

Funding from the National Multiple Sclerosis Society and the National Institutes of Health supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

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