State to let patients grow their own pot

By DIANA DEL MAURO | The New Mexican
June 28, 2007

When lobbyists rallied this year at the Roundhouse to legalize medical marijuana, they distinctly said patients wouldn’t be growing this mind-altering herb. Rather, the state Health Department would create a secure production and distribution system — the first state to do so.

After years of failed attempts, the measure won approval, making New Mexico the 12th state with such a law.

Now, as the law is about to go into effect Sunday, the message has changed. In a surprise move Thursday, the Health Department unveiled a provision that allows patients to grow a limited number of marijuana plants with protection from state prosecution.

That angered the law-enforcement community. Jim Burleson, director of the state sheriffs’ and police association, said having individual growers in the state could be a big problem.

“If a person is growing their own (marijuana), there is no quality control and no quantity control — and it’s absolutely contrary to what was discussed at the (legislative) session,” he said.


Also, it “sets up” patients for a high amount of scrutiny from federal law-enforcement agencies, he added. Using or distributing marijuana is illegal under federal law, and state law cannot protect violators from federal prosecution.

The Health Department says qualified patients and caregivers may cultivate as many as four mature marijuana plants and three immature marijuana seedlings. The rule also gives the Health Department the power to audit the number of plants at a patient’s home, said Dr. Steve Jenison, the program’s medical director.

Jenison said even if a state-licensed production and distribution system is put in place, patients would still have the option to grow marijuana plants at home.

Jenison said the Health Department decided to allow patients to grow pot because a state-run system could be months in the making, if it happens at all. Under the new law, the Health Department is supposed to issue rules about developing the production and distribution system by Oct. 1.

Because of a potential conflict between state and federal law (the federal government still views marijuana as an illicit drug that has no medicinal properties), the Health Department is seeking advice from the Attorney General’s Office for the best way to carry out that aspect of the new law.

“We cannot proceed ... until we have a better understanding of the legal implications,” Jenison said.

Burleson was unaware of this development until the Health Department issued a news release about the Medical Cannabis Program on Thursday. Though the Health Department invited various law-enforcement associations to planning meetings about how to implement the new law, most refused to participate.

Burleson said the association’s lawyer warned against taking part in the planning sessions, “lest we be considered co-conspirators in distributing a controlled substance.”

Jenison said the Health Department won’t give patients information on where to obtain seeds or plants or how to grow marijuana.

But Burleson asks, “Where is the first seed or plant going to come from? That’s going to be the first illegal act.”

Patients who don’t want to grow marijuana must find a way to obtain their medicine on the black market — at least for now. Patients and caregivers on the state’s registry can possess up to 6 ounces of marijuana and be protected from state prosecution, as long as they don’t use it fraudulently.

“This program is about providing much-needed relief for New Mexicans suffering from debilitating diseases,” Dr. Alfredo Vigil, the new health secretary, said in a news release. “We will also monitor the use of medical marijuana and prevent abuse.”

The law is limited to people with conditions such as cancer, HIV-AIDS, glaucoma and multiple sclerosis.

Contact Diana Del Mauro at 986-3066 or dianadm@sfnewmexican.com.


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Calcium ions activate enzymes in MS

Learning exactly how the myelin sheath is degraded might enable scientists to determine how to halt disease progress and reverse damage by growing new myelin, said Ji-Xin Cheng, an assistant professor in Purdue University's Weldon School of Biomedical Engineering and Department of Chemistry.

"Although multiple sclerosis has been studied for many years, nobody knows exactly how the disease initially begins," he said. "The pathway is not clear."

Purdue researchers used an imaging technique called coherent anti-Stokes Raman scattering, or CARS, to study how the myelin sheath is degraded by a molecule called lysophosphatidylcholine, known as LPC. The LPC does not cause multiple sclerosis, but it is used extensively in laboratory research to study the deterioration of myelin, which insulates nerve fibres and enables them to properly conduct impulses in the spinal cord, brain and peripheral nervous system throughout the body.




The findings suggest that LPC causes sheath degradation by allowing an influx of calcium ions into the myelin. The increased concentration of calcium ions then activates two enzymes - calpain and cytosolic phospholipase A2 - that break down proteins and lipids.

"It is possible that the same pathway causes myelin degradation in people suffering from multiple sclerosis and spinal cord injuries," Cheng said.

The research demonstrates that CARS microscopy is a valuable research tool and could become a future clinical method to diagnose multiple sclerosis and detect damage to the spinal cord from accident trauma, which also causes the myelin to degrade, he said.

The researchers used CARS to study and take images of healthy and diseased myelin. The researchers showed that an enzyme called cytosolic phospholipase A2 contributes to myelin degradation by snipping off one of the two tails that make up lipid molecules contained in the myelin. Cutting off one of the tails turns the lipid molecules into LPC, amplifying the effect and further degrading the myelin.

The research was carried out in spinal cord tissues extracted from animals and in the sciatic nerves of living mice.

Findings were confirmed by comparing CARS results with electron microscope images and measurements of electrical impulses in spinal cord tissue that distinguish between normal and diseased myelin.

CARS imaging takes advantage of the fact that molecules vibrate at specific frequencies. In a CARS microscope, two laser beams are overlapped to produce a single beam having a new frequency representing the difference between the original two beams. This new frequency then drives specific molecules to vibrate in phase, amplifying the signals from those molecules.

Contact: Purdue University's Weldon School of Biomedical Engineering

Study finds men and women with MS equally transmit genetic risk to offspring

Published: Thursday, June 28, 2007 | 12:42 PM ET
Canadian Press

TORONTO (CP) - A study of Canadian families with a parent who has multiple sclerosis has found men and women transmit the genetic risk of MS equally to their children.

The study, published Wednesday in the online edition of the journal Neurology, contradicts an earlier finding that fathers with MS were more likely than affected mothers to pass on the risk for the disease.

For this latest study, the researchers looked at 3,088 families with one affected parent and found that among the 8,401 children, there were 798 with multiple sclerosis.

In the end, they found equal transmission of the genetic risk to children, at 9.4 per cent for fathers, compared to 9.8 per cent for mothers.

Dr. George Ebers, a professor of clinical neurology at the University of Oxford, says his study involved 16 times as many people as the previous research, which had found dads were more likely than moms to transmit the risk of developing MS.

This new study also found no difference in the numbers of daughters and sons receiving the genetic risk of the disease from their parents.

Continue Article

"Intriguingly, we also found when half-siblings both have MS, there is a clear maternal effect, with mothers much more likely to be the common parent," Ebers said in a release.

The families studied had children born before 1980, so offspring would have at least reached the peak age for the onset of multiple sclerosis, which is estimated at 25 to 30 years old.

If families had both parents affected by the disease, they were removed from the analysis.

© The Canadian Press, 2007

Oral Tysabri steps up to the plate

By Anna Lewcock

27/06/2007 - With a number of companies competing in the race to develop the first oral treatment option for multiple sclerosis, UCB and Biogen Idec's oral version of the infamous Tysabri has entered Phase II trials.

The two companies' candidate, currently going by the name CDP323, is an oral VLA-4 antagonist (as is Tysabri) intended for the treatment of relapsing-remitting multiple sclerosis (MS). The Phase II trials are expected to yield results by the end of 2008.

Biogen Idec hopped on board to partner with UCB in developing and commercialising the small molecule compound back in October last year, following encouraging Phase I trials. The two companies are initially investigating the compound for the treatment of MS, but will also be considering its use in treating other autoimmune disease indications.

UCB and Biogen are co-developing and co-commercialising the compound, with all commercialisation costs and profits to be shared equally. Over $200m (€149m) will be added to UCB's coffers courtesy of the Biogen deal.

CDP323 is one of the few oral alpha-4 integrin antagonists according to UCB, and it's hoped that by tapping Biogen's expertise in multiple sclerosis the two companies can come up with a competitive product.

Biogen is already responsible for the market-leading MS drug worldwide, Avonex (interferon beta-1a), which brought the company revenues of around $1.7bn over 2006. However, the company ahs taken a few punches over the last few years regarding an existing injectable MS treatment, Tysabri (natalizumab).

Tysabri, also a VLA-4 antagonist, was approved by the US Food and Drug Administration (FDA) for relapsing-remitting forms of MS back in 2004, however was hastily withdrawn three months later after several cases of patients developing a life-threatening viral infection of the brain.

The occurrence of progressive multifocal leukoencephalopathy (PML) in certain patients held Tysabri of the market for a significant period of time, only returning with stringent guidelines in June last year.

Damage to Biogen and Tysabri partners Elan's potential revenues was significant, with original analyst estimates for the treatment predicting annual revenues of up to $3bn, but following its withdrawal and late relaunch the drug only managed to generate $74m over 2006 - split between Elan and Biogen.

Although the companies have initiated risk management plans in the US and Europe to facilitate the correct use of Tysabri, the firms clearly recognise that the damage have may have already been done, with Biogen foreseeing "many rumours and speculation regarding Tysabri and suspected cases of PML" in the future.

Despite the unfavourable aura surrounding the existing version of Tysabri, a spokesperson for UCB told in-PharmaTechnologist.com that the two companies "strongly believe an oral solution is worthwhile exploring," and that the product could potentially become one of the firm's bigger products.

A 24-hour oral formulation of the drug could have significant advantages over the current monthly version of Tysabri in that it could reduce the likelihood of PML taking hold in a patient, as well as the more obvious non-invasive aspect of drug administration.

It's perhaps unsurprising that Biogenis hoping to catch the next big wave in MS treatment by successfully producing an oral formulation whilst simultaneously reaffirming its position in the MS market and hopefully demonstrating the safety of a Tysabri-like treatment option.

In addition to this, the MS market is growing fairly rapidly, and the first non-invasive oral treatment to become available would earn itself a particularly favourable position and at least a temporary monopoly while competitors catch up.

Several firms are fighting to be the first on the market with a non-invasive treatment option for MS sufferers. Only earlier this month Teva and partners Active Biotech announced their oral candidate was entering Phase II trials, and Novartis' hotly tipped oral MS treatment (FTY720, fingolimod) is on track for submissions in 2009.

Insight into myelination process

In a host of neurological diseases, including multiple sclerosis (MS) and several neuropathies, the protective covering surrounding the nerves is damaged. Scientists at the Weizmann Institute of Science have discovered an important new line of communication between nervous system cells that is crucial to the development of myelinated nerves – a discovery that may aid in restoring the normal function of the affected nerve fibres.

Weizmann Institute scientists Prof. Elior Peles, graduate student Ivo Spiegel, and their colleagues in the Molecular Cell Biology Department and in the United States, have provided a vital insight into the mechanism by which glial cells recognize and myelinate axons.

The Weizmann Institute team found a pair of proteins that pass messages from axons to glial cells. These proteins, called Necl1 and Necl4, belong to a larger family of cell adhesion molecules.

Peles and his team discovered that even when removed from their cells, Necl1, normally found on the axon surface, and Necl4, which is found on the glial cell membrane, adhere tightly together. When these molecules are in their natural places, they not only create physical contact between axon and glial cell, but also serve to transfer signals to the cell interior, initiating changes needed to undertake myelination.

The scientists found that production of Necl4 in the glial cells rises when they come into close contact with an unmyelinated axon, and as the process of myelination begins. They observed that if Necl4 is absent in the glial cells, or if they blocked the attachment of Necl4 to Necl1, the axons that were contacted by glial cells did not myelinate. In the same time period, myelin wrapping was already well underway around most of the axons in the control group.

“What we’ve discovered is a completely new means of communication between these nervous system cells,” says Peles. “The drugs now used to treat MS and other degenerative diseases in which myelin is affected can only slow the disease, but not stop or cure it. Today, we can’t reverse the nerve damage caused by these disorders. But if we can understand the mechanisms that control the process of wrapping the axons by their protective sheath, we might be able to recreate that process in patients.”

Contact: Weizmann Institute of Science

New Rebif (Interferon Beta-1a) Initiation Pack For Patients With Relapsing Remitting Multiple Sclerosis

Merck Serono has announced the launch of a new Rebif initiation pack for patients with relapsing remitting multiple sclerosis (RRMS). It is important when patients begin interferon beta therapy that the dose is gradually increased over a four week period as this helps minimise possible side effects. The new pack consists of 12 pre-filled syringes at the recommended staged dosing to enable easy titration and minimal wastage as a patient begins therapy.

Gradual dose titration when starting treatment may minimise side effects such as flu-like symptoms that can occur with interferon beta therapy1. Flu-like symptoms occur in 40% of patients2 and are typically present within the first few days of commencing treatment. Most patients will also experience injection site reactions, predominantly mild inflammation. Whilst both side effects are in the majority of cases reversible and may alleviate over time, they have been shown to decrease the potential for concordance. In a retrospective study among 281 patients, injection site reactions and flu-like symptoms were cited among the top three reasons for interrupting interferon beta therapy3.

Debbie Quinn, MS Specialist Nurse at Northamptonshire Teaching PCT commented on the new initiation pack. "It is really important when you start a patient on interferon beta therapy that you manage their expectations in terms of the likely side effects, building up to the maintenance dose over an extended period of time limits these symptoms. Delivering the syringes in an easy to use pack simplifies the titration process for patients and is reassuring for them."

Starting treatment for MS can be a stressful experience for patients and their carers and it has been shown that patients who do have a more positive experience during the initial stages of therapy will be more likely to adhere to treatment in the long term. Long term follow up has demonstrated the benefits of interferon beta over a 7-8 year period and supports the importance of initial concordance4, 5.

-- The Rebif initiation pack contains 12 pre-filled syringes (six with 8.8μg and six with 22μg)

-- Rebif should be taken three times a week at approximately the same time each day and the injections should be at least 48 hrs apart

-- A Rebif initiation pack covering a four week course of treatment costs £586.196

-- The titration schedule consists of 2 weeks' treatment at 8.8μg, followed by a further 2 weeks at 22μg, building up to a maintenance dose of 44μg at week 5 and is based on the schedule used during the landmark trials7

About Merck Serono

Merck KGaA of Darmstadt, Germany, is a global pharmaceutical and chemical company with sales of EUR 6.3 billion in 2006, a history that began in 1668, and a future shaped by about 35,000 employees (including Merck Serono) in 56 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 a 73% interest and free shareholders own the remaining 27%. The former U.S. subsidiary, Merck & Co., has been completely independent of the Merck Group since 1917.

http://www.serono.com

References

1. Wroe SJ. J Int Med Res. 2005;33:309-18
2. Rebif SPC
3. Tremlett and Oger. Neurology 2003;61:551-554
4. Kappos L et al. Neurology 2006;67:944-953
5. World Health Organisation Report 2003; Please click here.
6. Rebif Initiation Pack Prescribing Information, May 2007
7. PRISMS Study Group. Lancet 1998;352:1498-1504

MediciNova Announces New Strategic Initiative

SAN DIEGO, Jun 26, 2007 (PrimeNewswire via COMTEX News Network) -- MediciNova, Inc., a biopharmaceutical company that is publicly traded on the Nasdaq Global Market (Nasdaq:MNOV) and the Hercules Market of the Osaka Securities Exchange (Code Number: 4875), today announced that based on recent clinical successes and evaluation of market opportunities, it will focus its resources on development and commercialization of two key assets in its development pipeline, MN-221 and MN-166. MediciNova believes that MN-221, now in Phase IIa clinical testing, has the potential to become the new standard of care for the treatment of severe, acute exacerbations of asthma (status asthmaticus) in emergency facility settings. Data from the Phase IIa trial is expected during the fourth quarter of 2007. MN-166, an oral treatment for multiple sclerosis, demonstrated positive clinical benefits and a superior safety profile after one year of treatment in a two-year randomized, double-blind, placebo-controlled Phase II trial in 297 relapsing multiple sclerosis patients.

Adhering to its strategy to focus investment on key assets such as MN-221 and MN-166, and in order to bring these assets substantially forward towards commercialization, MediciNova will limit its expenditures on other development programs to only those activities necessary to maximize each asset's value, while aggressively pursuing a variety of initiatives to monetize these development programs. As part of this strategy, MediciNova will discontinue development of MN-001 in its current immediate-release formulation. As such, the current Phase III trial of MN-001 in bronchial asthma patients will be stopped. To date, approximately 200 patients have been enrolled in that trial with no reported serious adverse events. The formulation currently being tested requires a multiple dosing per day schedule. Market and competitive analyses point to the desire for a once-a-day therapy for bronchial asthma and, thus, MediciNova will continue its work on developing a once-a-day preparation of MN-001. MediciNova anticipates that this reallocation of resources will provide substantial cash savings over the next 12 months.

"MediciNova's strategy has always been to select and develop product candidates that fill an unmet medical need and offer competitive market advantages. To that end, we have built an attractive pipeline that provides us with multiple opportunities from which to realize value," said Yuichi Iwaki, M.D., Ph.D., President and Chief Executive Officer of MediciNova, Inc. "In focusing our resources, we are in the enviable position to dedicate investment to two commercially attractive development candidates that we can potentially commercialize on our own with a small, focused sales force, while we simultaneously continue efforts to monetize the remainder of our pipeline through business development initiatives, including potential partnering opportunities. We believe this new strategy will provide even greater value in the realization of our key clinical assets."

About MediciNova

MediciNova, Inc. is a publicly-traded biopharmaceutical company that acquires well characterized small-molecule drugs through strategic alliances with Japanese and other international pharmaceutical companies and accelerates their development in a diversified portfolio of therapeutic product candidates targeting significant disease markets. MediciNova's pipeline, which includes six compounds in clinical testing, targets a variety of prevalent medical conditions, including asthma, multiple sclerosis, status asthmaticus, interstitial cystitis, cancer, Generalized Anxiety Disorder, insomnia, preterm labor, urinary incontinence and thrombotic disorders. MediciNova's strategy is to commercialize selected product candidates in the United States and to monetize other programs at key value inflection points. For more information on MediciNova, Inc., please visit www.medicinova.com.

The MediciNova, Inc. logo is available at http://www.primenewswire.com/newsroom/prs/?pkgid=3135

Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding MediciNova's clinical trials supporting efficacy of product candidates and the potential novelty of such product candidates as treatments for disease, plans and objectives for present and future clinical trials and product development, strategies, future performance, expectations, assumptions, financial condition, liquidity and capital resources. These forward-looking statements may be preceded by, followed by or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "would," or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements, include, but are not limited to, the risks and uncertainties inherent in clinical trials and product development and commercialization, such as the uncertainty in results of clinical trials for product candidates, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, MediciNova's reliance on third parties and the timing, cost and design of future clinical trials and research activities, the failure to execute strategic plans or strategies successfully, MediciNova's collaborations with third parties, and the other risks and uncertainties described in MediciNova's filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2006 and its subsequent periodic reports on Forms 10-Q and 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intent or obligation to revise or update these forward-looking statements.

This news release was distributed by PrimeNewswire, www.primenewswire.com

SOURCE: MediciNova, Inc.

MediciNova, Inc.
Shintaro Asako, Chief Financial Officer
858-373-1500
info@medicinova.com

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UCB and Biogen Idec's Oral VLA-4 Antagonist Enters Phase II Development for Multiple Sclerosis

Brussels (Belgium) and Cambridge, MA (USA) June 26, 2007 UCB (Euronext Brussels: UCB) and Biogen Idec (NASDAQ: BIIB) today announced the initiation of a Phase II study of CDP323 an oral VLA-4 antagonist under development for relapsing-remitting multiple sclerosis (MS). The double-blind, randomized Phase II study commenced this week with dosing of the first patient. The study is designed to enroll over 200 patients with relapsing-remitting MS who have failed earlier treatment with a beta-interferon. Last October the companies entered an agreement to co-develop and co-commercialize this small molecule compound.

The trial compares the safety and efficacy of two doses of CDP323 monotherapy to placebo over a period of six months. This is the first time that patients with MS will be exposed to CDP323. Approximately 50 medical centers in Europe and the U.S. are expected to participate in this study. The results of this Phase II study are expected by the end of 2008.

"Multiple sclerosis affects more than a million people worldwide and so far, no oral treatment has been available. An oral therapy would represent a significant advance for patients as it could provide them with a new, non-invasive option of drug delivery, said Professor Chris Polman, Professor of Neurology, VU Medical Centre, Amsterdam, the Netherlands, Lead Investigator for this study.

About CDP323
CDP323 is an orally active small molecule VLA-4 antagonist. The safety, tolerability and pharmacokinetic profile of CDP323 have been evaluated in healthy volunteers in three separate Phase I studies. Data from these studies were reported at the 2006 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The data from these early studies supports further development of CDP323.

About Multiple Sclerosis
MS is a chronic disease of the central nervous system that affects approximately 400,000 people in North America and more than one million people worldwide. It is a disease that affects more women than men, with onset typically occurring between 20 and 50 years of age. MS is caused by damage to myelin, the protective sheath surrounding nerve fibers in the central nervous system, which interferes with messages from the brain to the body. Symptoms of MS may include vision problems, loss of balance, numbness, difficulty walking and paralysis.

About UCB
UCB (www.ucb-group.com) is a leading global biopharmaceutical company dedicated to the research, development and commercialisation of innovative pharmaceutical and biotechnology products in the fields of central nervous system disorders, allergy/respiratory diseases, immune and inflammatory disorders and oncology. UCB focuses on securing a leading position in severe disease categories. Employing over 8,500 people in over 40 countries, UCB achieved revenue of 2.5 billion euro in 2006. UCB is listed on the Euronext Brussels Exchange and its worldwide headquarters are located in Brussels, Belgium.

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

UCB and Biogen Idec Safe Harbor
This press release contains forward-looking statements regarding the development of CDP323. Drug development involves a high degree of risk. Only a small number of research and development programs result in commercialization of a product. Factors which could cause actual results to differ materially from UCB™s and Biogen Idec™s current expectations include the risk that the companies may not be able to demonstrate the safety and efficacy of CDP323 at each stage of the clinical trial process; technical hurdles relating to the manufacture of CDP323 may be encountered; applicable regulatory standards may not be met or regulatory authorities may fail to approve CDP323; and other unexpected hurdles may be encountered.

For more detailed information on the risks and uncertainties associated with Biogen Idec's drug development activities, see the section entitled Risk Factors in Biogen Idec's quarterly report on Form 10-Q for the fiscal quarter ended March 31, 2007 which was filed with the Securities and Exchange Commission, as well as other periodic and current reports of Biogen Idec filed with the Securities and Exchange Commission. Biogen Idec assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

For more information contact:

UCB
Media and Investors:
Jean-Christophe Donck
+32 2 5599346

Investors:
Marieke Mohr
+32 2559 9264

Biogen Idec
Media:
Amy Brockelman Reilly
617-914-6524

Investors:
Eric Hoffman
617-679-2812

Promising prescription: $5.5B market waiting as Pipex tests 2 drugs

By Andrew Dietderich

6:00 am, June 25, 2007

An Ann Arbor-based company that’s moving to the American Stock Exchange today plans to tap at least two drug markets that could be worth a total of $5.5 billion annually, using drugs licensed from the University of Michigan and the University of California at Los Angeles.

Two weeks ago, Pipex Pharmaceuticals Inc. (Amex: PP) received $5 million from the National Multiple Sclerosis Society, the largest grant ever given by the organization.

Pipex has six drugs in its pipeline, but two are closest to going to market: Trimesta and Coprexa.

Trimesta is used to treat multiple sclerosis; and Coprexa is used to treat Wilson’s disease, which destroys the lungs.

Pipex was founded in Miami in 2001 by Steve Kanzer, the company’s chairman and CEO. A biotech investor, Kanzer moved Pipex to Michigan in 2004 to be nearer to the talent pool in Ann Arbor.

“Florida is working on its biotech industry. But there is so much more talent in Michigan, I decided to come here,” he said.

That’s not the only reason, though.

The compound for Coprexa is licensed from UM. Coprexa has been through two clinical trials and treats a disease called idiopathic pulmonary fibrosis — the technical name for Wilson’s disease, which kills about 128,000 people in the United States annually.

“The technology came out of the University of Michigan, so it really speaks to the kind of talent and money that is available in the Ann Arbor area,” said Tim Robinson, vice president of operations at Ann Arbor Spark, the economic development association for the Ann Arbor area.

Kanzer said there is no treatment for Wilson’s disease, and the potential market for the drug is $5 billion annually.

Pipex plans to file its application for approval for Trimesta in late 2009. The drug was discovered by a UCLA researcher who found that a specific hormone in the placenta of pregnant women with multiple sclerosis helped with remission of the disease and reduced lesions in the brain by 80 percent.

The drug, also licensed by Pipex, has completed phase II clinical trials.

Kanzer said the potential U.S. market for that drug is worth $500 million annually.

Pipex completed $13.9 million in private-equity financing in the fourth quarter and went public at the end of April.

Besides UM and UCLA, the company has agreements with McLean Hospital at Harvard University, the University of Southern California and Children’s Hospital-Boston.

Pipex recently completed a new lab in Ann Arbor. The company has 18 employees — four from Esperion Therapeutics Inc., including the co-founder and co-developer of Lipitor, Charles Bisgaier. He is Pipex president and a member of the board.

Pipex has a way to go when it comes to finances, though.

In the first three months of the year, the company reported a net loss of $2.8 million or 90 cents a share. It does research and development and didn’t have any revenue.

Collaborating for a cure

Volunteers offer blood and histories for MS research

By Elizabeth Cooney TELEGRAM & GAZETTE STAFF
ecooney@telegram.com



Gena K. White plays with her son, Will, 2, as she has blood drawn for a database being created for the Accelerated Cure Project at the Multiple Sclerosis Center at UMass Memorial in Worcester. Tuesday afternoon. The White family drove up from Blythewood, S.C., to become part of the project.

It’s about time.

Research takes time when the goal is figuring out the cause — or more likely, causes — of a baffling disease such as multiple sclerosis. But for the people who have the degenerative neurological disease, time is what they don’t have.

MIT engineer and computer networking entrepreneur Art Mellor, diagnosed with MS seven years ago at age 37, saw the need to speed up the pace of research in two ways. He recognized that scientists spread out across the country and the world didn’t have enough information or tissue samples to tell them about how MS and related diseases might unfold. And he saw how isolated these investigators were from one another, reflecting how science is done in academic and industry labs that need to win grants or develop drugs.



The Accelerated Cure Project for Multiple Sclerosis wants to find the causes of MS by creating a repository of detailed information and blood, spinal fluid and other samples from people with the disease and from family members without the disease. Six sites across the country, including UMass Memorial Medical Center in Worcester, are seeking a total of 1,000 volunteers in its first phase to share their histories and lab work that researchers can study. In turn, those researchers must agree to share what they learn. Mr. Mellor and his partners believe this kind of collaboration will yield progress far more quickly than individual efforts under way in many MS centers.

“We can effectively multiply the value of research results through sharing,” he said.

No one knows the cause of MS. There is a strong suggestion from studies that heredity and environment play interwoven roles, but more work needs to be done to tease out those influences. The dearth of large-scale trials was a shock to Mr. Mellor when he and some colleagues set out to create what they call the Cure Map, which is an analysis of all the literature into the causes of MS.

“We thought at first we would locate the holes in the cloth of research and figure out what needed to be patched,” he said. “We determined that the cloth of research was all holes.”

So Mr. Mellor quit his job, started the project and began working with Beth Israel Deaconess Medical Center in Boston and UMass Memorial in Worcester to figure out how to create a network of sites to gather biological specimens and patient histories. It will cost the Accelerated Cure Project $2 million to $2.5 million to complete those 1,000 collections.

Three were added last week when the White family drove up from their home in Blythewood, S.C., to become part of the project.

They had been searching for trials for their 2-year-old son, Will, who was diagnosed with transverse myelitis when he was 5 months old. Transverse myelitis is inflammation of the spinal cord that can occur in MS.

The Whites heard about the Accelerated Cure Project in a TM newsletter. They’d been disappointed that their son was too young to become part of experiments to see what might restore the movement that he has lost from his waist down.

The Accelerated Cure Project isn’t a clinical trial in the sense that therapies are tested. Instead it offers the foundation for questions that may one day lead to answers, Mr. Mellor explained.

The Whites were eager to be involved.

“We were thrilled when we talked with Janice,” Mrs. White said.

Janice Weaver is the UMass Memorial coordinator for the project. She has completed information and samples from 125 people since September. Will was the first child to be included. She explained to Mrs. White that the nine vials of blood taken from each family member — the equivalent of 4 tablespoons — would be frozen and stored for tests that might look at DNA, white blood cell counts or some as yet unknown component of a future researcher.

Will lay across his mother’s lap as Kathleen O’Leary, the head research coordinator, drew his blood. He looked concerned when it was his mother’s turn, but she soothed him as she lifted him up with one arm as her blood was taken from the other.

Their trip is worth the effort, Mr. White said firmly. Three days before their appointment, they had loaded up the family van with Will, his 4-year-old sister, Dorothy Rose, his wheelchair and new dual DVD players to come to Worcester.

Johns Hopkins University is the lead site, but its internal review board had not yet given approval for children to be included in the project. The other sites are the University of Texas Southwestern Medical Center in Dallas, the Multiple Sclerosis Research Center of New York, Barrow Neurological Institute in Phoenix and the Shepherd Center in Atlanta. Beth Israel Deaconess in Boston did not continue after the pilot phase.

Dr. Peter Riskind, director of the MS Center at UMass Memorial, has been involved in the project for about five years. He welcomes the approach, which he thinks can work well in parallel with individual research supported by organizations such as the National MS Society, on whose clinical advisory council he sits.

“We don’t have anything like this” collaboration, he said. “This is a very different approach that we hope will be very helpful in terms of fertilizing ideas. I think it’s wonderful.”

Project founder Mr. Mellor sees himself as part of a movement by patients and family members of patients to move research forward.

“It really takes people who feel the clock ticking,” he said.

For more information, go to www.acceleratedcure.org.

Lipid-Lowering Drugs Protect Against Peripheral Diabetic Neuropathy

A major epidemiological study conducted over eight years in Australia has shown that two classes of lipid- lowering drugs -- statins and fibrates -- significantly lower the risk of developing nerve damage known as peripheral sensory diabetic neuropathy, according to a report presented today at the American Diabetes Association's 67th Annual Scientific Sessions.

"Statins and fibrates, drugs already highly recommended for people with type 2 diabetes to help prevent heart attacks, now also appear to help prevent one form of diabetic nerve damage called 'peripheral neuropathy,' a common complication of diabetes," said Timothy Davis, MD, PhD, Professor of Medicine, at the University of Western Australia, and principal investigator of the study, in a recent interview. "Statins or fibrates reduced the risk of developing peripheral neuropathy by 35% or 48%, respectively, although these should be considered comparable risk reductions because of the wide confidence intervals." A correct estimate falls into a statistical range called a confidence interval, and the range in this instance means that the two estimates are indistinguishable, statistically speaking.

Peripheral neuropathy is the most common form of nerve damage caused by diabetes, affecting approximately 50% of those with diabetes. Damaged nerves can cause stinging or burning sensations, tingling, pain, numbness or weakness in the hands and feet. Although many medications have been used to treat the condition's symptoms, many fail, and preventing the condition by means other than controlling blood glucose levels, has also proven difficult. The project was essentially two studies in one: a large cross-sectional snapshot and a longitudinal five-year study of a subsection of the larger group.

Nearly 21 million Americans have diabetes, a group of serious diseases characterized by high blood glucose levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as heart disease, blindness, kidney disease, nerve damage, and amputations. It is the fifth leading cause of death by disease in the U.S.

All of the study participants had type 2 diabetes, which involves insulin resistance -- the body's inability to properly use its own insulin. Type 2 used to occur mainly in adults who were overweight and ages 40 and older. Now, as more children and adolescents become overweight and inactive, type 2 diabetes is occurring more often in young people.

METHODOLOGY AND FINDINGS

The researchers assessed the relationship between lipid-lowering therapy and the prevalence and incidence of peripheral neuropathy, based on scoring on the Michigan Neuropathy Screening Instrument -- one of the most sensitive and specific tools for screening for the condition -- in a large representative cohort of adults. Prevalence measures how much of a disease or condition there is in a population at a particular point in time. Incidence measures the rate of occurrence of new cases of a disease or condition.

The cross-sectional sample was comprised of all 1,294 of those recruited to the Fremantle Diabetes Study between 1993 and 1996.

At their entrance into the study, the participants average age was 64 years, with their diabetes diagnosed four years previously, 48.8% were male, and 30.9% had neuropathy. Fibrates and statins were used by 3.5% and 6.8%, respectively.

Older age, longer diabetes duration, central adiposity, increasing height, higher fasting plasma glucose, higher systolic blood pressure, higher urinary albumin to creatinine ratios, and indigenous racial background were all independently associated with prevalent peripheral neuropathy at baseline, while use of fibrates was associated with a 70% reduction in neuropathy prevalence.

The longitudinal sub-group was comprised of 531 people who had attended six comprehensive annual health assessments by November 2001. Use of fibrates and statins increased to 10.4% and 36.5%, respectively, during the five years of follow-up. The results were controlled for potential confounding variables, including changes in A1C levels, a measure of long-term blood glucose control.

Time to development of newly diagnosed peripheral neuropathy in the longitudinal sub-group showed that fibrates and statins reduced neuropathy risk by 48% and 35% respectively. Further, they may have independent action. "In our analysis, the beneficial effects of the drugs were independent of each other and they may work through different mechanisms," said Dr. Davis. "It's just a hypothesis, but taking both drugs may yield greater benefit than taking either drug alone."

At the outset, in the cross-sectional study, the fibrate participants were using gemfibrozil, and the statins in use were atorvastatin, simvastatin and pravastatin. At the end of the longitudinal study, gemfibrozil continued to be the primary fibrate used, although some had begun to use fenofibrate. By then atorvastatin was the predominant statin, although simvastatin and pravastatin also continued to be in use.

"We believe these benefits are class effects of these drugs," said Dr. Davis. While many mechanisms have been proposed, their mechanism of action in neuropathy remains unknown. The leading theory for statins seems to be a reduction of both inflammation and oxidative stress.

RECOMMENDATIONS

Although laboratory and animal studies have provided evidence that both statins and fibrates may protect against nerve damage, anecdotal clinical reports have associated their use with a reversible clinical neuropathy. In light of the new findings, Dr. Davis suggested that such reports may have been coincidence -- the individuals were developing neuropathy anyway -- or perhaps that there may be a small number of people who were sensitive to the drug but, he emphasized, with greater numbers who may benefit from taking it.

"People with diabetes should not shy away from taking these drugs for both heart and neuropathy benefits," he said. "Whether a fibrate or statin should be taken is never an easy choice, but a statin is usually the first line drug because of the strong evidence of cardiovascular disease prevention benefits."

Co-authors with Dr. Davis were Bu Yeap, MD, PhD, David G. Bruce, MD, PhD, and Wendy A. Davis, PhD, all of the University of Western Australia.

The American Diabetes Association is the nation's leading voluntary health organization supporting diabetes research, information and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities.

American Diabetes Association
http://www.diabetes.org

Botox Treatment for the Bladder

Botox Inhibits Bladder From Contracting
By Denise Dador

June 21, 2007 (KABC-TV) - Frequency means having to go to the bathroom at least every hour. Urgency means you just can't wait. You've got to go right now. If these symptoms sound familiar, you might want to consider enrolling in a clinical trial for a drug many people are familiar with.

Erika Lopez's job as an associate producer for Mix Magazine keeps her on the go. But every 20 minutes, she'd have to stop what she's doing.

Lopez: "It was a big inconvenience everywhere I went. I had to revolve my life around where I could find a bathroom."

Multiple sclerosis caused Erika to have incontinence and an overactive bladder.

Lopez: "I've been on medication, I've done cathetering, I've done everything you might imagine."

A few months ago, she decided to enroll in an unusual clinical trial that involves injecting Botox in her bladder. Botox is widely known as a facial wrinkle remover.

David Ginsberg, USC Keck School of Medicine: "So instead of injecting Botox, let's say into the brows and taking your wrinkles out, you can inject a small amount of the Botox into the bladder, throughout the bladder."

The needle is inserted through the urethra using a cystoscope. The effect lasts about six to nine months.

The procedure is done right in the doctor's office. It takes about five minutes. Patients will receive anywhere from 100-200 units of Botox and it usually takes about 10 to 20 injections.

The Botox inhibits Lopez's bladder from contracting.

And while Dr. Ginsberg says most patients tolerate the procedure well, Erika says she felt a lot of discomfort.

Lopez: "The level of discomfort is somewhat like childbirth ... The results have been equally as rewarding."

Erika's symptoms of frequency and urgency have completely disappeared. But in her case the Botox has worked a little too well.

Dr. Ginsberg: "I think probably the biggest two risks are that are that it doesn't work, or it works so well you can't go. That would be temporary."

It happens in about 10 percent of patients. Despite this side effect, Erika says the Botox injections have greatly improved her quality of life.

Lopez: "I do injections for MS and then I do that, and I'm a healthy, happy, lively woman."

To find out if you're eligible for the trial or to get more information, call Charlotte Lee at (323) 865-3774, or visit https://www.praxisdirectstudies.com/Dignity/Default.aspx?PageName=FindPhysician.

Copyright © 2007 KABC-TV. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

Scientists decry President Bush's veto of stem-cell bill

Senate may yet override decision, but House falls short of needed votes.

Meredith Wadman

For the second time in less than a year, President George W. Bush yesterday vetoed legislation that would lift restrictions on US federal funding for human embryonic stem-cell research. The bill, passed by the Senate and the House, allows government funding for research on stem cells derived from embryos that are left over at fertility clinics and slated for destruction. "I will not allow our nation to cross this moral line," Bush said.

Bush also announced that he had signed an executive order — without new money attached — directing the government to support research on stem cells derived without creating or destroying embryos. He cited as an "exciting" example of this, three recent papers reporting the reprogramming of mouse skin cells into cells that seem indistinguishable from embryonic stem cells (see 'Simple switch turns cells embryonic'). This work was only done in mice, and the cells came with associated problems that would make them unsafe for therapeutic use.

Scientists, scientific societies and congressional critics decried the veto and dismissed the executive order as a red herring. The American Association for the Advancement of Science said that the order "is not a substitute" for the vetoed bill and noted that the new approaches supported by the order seem to already be eligible for federal funding.

Not satisfactory

Kathrin Plath, a stem-cell biologist at the University of California, Los Angeles, said that Bush's order "doesn't satisfy me, because we have to study stem cells derived from fertility clinic embryos to understand what a human embryonic stem cell is all about." Plath, who was a senior author on one of the three recent papers referred to by Bush1, notes that her group's results haven't been reproduced with human cells yet. "Human reprogramming might just not work," she says.

Federal funding is currently limited to work on a score of human embryonic stem-cell lines derived before August, 2001.

A recent poll, published today in Science2, shows that 60% of more than 1,000 infertility patients responding to a survey would probably donate their unused embryos for stem-cell research rather then have them destroyed or donated to another couple. So should the bill succeed, there would probably be a large source of embryonic cells available for research.

The Senate is expected to try to override Bush's veto in the coming weeks, and may muster the two-thirds majority required to do so. The House of Representatives is several dozen votes short of a veto-proof majority.

New strategies to treat neurological disorders

By Mike Nagle

20/06/2007 - Experts from around the world have gathered this week to discuss the best emerging therapies for a number of neurological disorders such as multiple sclerosis and stroke.

Thousands of scientists and clinicians have descended on the island of Rhodes, Greece for the European Neurological Society (ENS) congress and the latest drugs are the centre of attention.

One central topic at the scientific conference is multiple sclerosis (MS), a chronic inflammatory disease that attacks the central nervous system (CNS).

"About 400,000 people in Europe have MS and about one million worldwide," said the ENS president, Professor Giancarlo Comi.

"MS is still not curable. A number of new findings have been made in recent years, however, with regard to the origins of the disease and new therapeutic strategies. These new insights help us to mitigate the course of the disease and delay the development of permanent disabilities."

The scientists took time to focus on the mechanisms underlying the process of axonal degeneration which characterise the progressive phase of the disease. There is some evidence that some of these mechanisms are at least partially independent from inflammation.

According to Prof. Comi, modulating and suppressing the immune system only has a modest effect at best on the progressive phase of the disease.

"One important goal in the treatment of this severe disease has to be to develop therapies that repair the damage MS causes in nerve cells," Professor Comi said. "There is increasing scientific evidence that the course of MS is shaped by different disease mechanisms in its early and late phase."

Researchers from France, Germany and Switzerland believe they have proof for a hypothesis first posited in the late 19th century. According to this new evidence, certain stem cells differentiate very early on in human development into nerve cells or into glia cells - the maintenance and support cells in the CNS.

They showed that there are two different types of stem cells that differentiate into either glia or nerve cells. This finding from Dr Zalc, Hôpital Pitié Salpêtrière, Paris, and colleagues, contradicts the viewpoint that nerve cells form first and that glia cells then develop from them.

Prof. Comi said: "Key fundamental research findings like these could well enable MS therapy to advance in significant ways."

Professor Martin Schwab, from the University of Zurich, presented promising results for his antibody therapy that can restimulate nerve growth in animals, following injury or stroke. In the human brain, nerve fibre growth is restricted to distances below 2mm as it is inhibited by several substances found in myelin sheaths - the protective coverings found on nerves.

One of these substances is the membrane protein Nogo-A. Prof. Schwab and his team have developed an antibody that blocks this target. When they tested its effect in animals, they found that the drug stimulated nerve fibre growth over comparatively long distances substantially improved "functional restoration", such as running, swimming or gripping.

Professor Ioannis Milonas, chairman of the ENS Congress, said: "The new agent is currently being tested in a Phase I clinical study in a European network of centres for spinal cord injuries."

Another possible stroke therapy discussed at the event was developed by a group of Swiss scientists from University Hospital Zurich. Annett Spudich and her colleagues are examining the effectiveness of multidrug resistance-associated protein 1 (MRP1) as a stroke therapy in mice. They injected mice subjected to stroke injury with MRP1 substrates 17betaEG and GSNO immediately and saw a dose-dependent decrease (17betaEG) or increase (GSNO) in brain injury. If MRP1 expression was knocked out completely, these injury effects were also blocked. This indicated that MRP1 was needed by the two substrates in order to gain access to the brain.

"Strokes are the third most common cause of death and the most common cause of severe disability for adults in industrialised countries," said Professor Gerard Said, secretary general of the ENS.

He continued: "They have found that MRP1 might be a substance for transporting drugs across the blood cerebrospinal fluid barrier, a physiological barrier between the central nervous system and the blood stream."

If this proves to be the case, MRP1 could be used as a gateway through which drugs could travel directly to the brain regions affected by a stroke.

DeGette's response to Bush veto

June 20, 2007

Rep. Diana DeGette, D-Denver, offered the following statement at a press conference in reaction to President Bush's second veto of the Stem Cell Research Enhancement Act.

"President Bush remains stubbornly defiant by once again vetoing potentially life-saving legislation that would give millions of patients and their families hope. Congress gave President Bush another opportunity to do the right thing, but once again he put politics before science.

"The president has become a roadblock to allowing this research to unlock doors to treatments and cures for numerous diseases and conditions — including diabetes, Parkinson's, and multiple sclerosis.

"I can understand why President Bush is hiding from the public to veto this legislation in private — he refuses to meet with us, he refuses to give ground, and he continues to turn his head to the promise of embryonic stem cell research.

"Today's Executive Order by President Bush is not a substitute for the promise of embryonic stem cell research.

"I support all forms of ethical stem cell research. However, the vast majority of scientists agree that embryonic stem cell research offers the greatest promise for developing treatments and cures for countless diseases and conditions. That is why I and a bipartisan majority of Congress feel strongly that we must allow federal funding for embryonic stem cell research.

"While I support these other methods of research, the consensus among the scientific community is that these methods are years behind the progress of embryonic stem cell research.

"An example of this progress was the recent announcement by British scientists that embryonic stem cells may be used to cure a form of macular degeneration within five years. This research was made possible by an anonymous donation from a U.S. donor, who has become frustrated by curbs on stem cell work in this country.

"A recent Gallup Poll found growing support among the American public; nearly 65 percent of the American people support embryonic stem cell research.

"Despite passing both Houses of Congress with broad, bipartisan majorities, the president again turns his back on Congress and the American people.

"The Senate gets it. The House gets it. The American people get it. Why doesn't the president?

"Every time the Congress overwhelmingly passes the stem cell bill, the president calls for additional research that is already under way. He can try to change the debate about stem cell research, but the facts remain: embryonic stem cell research shows the most promise, and is supported by a solid majority of the American public.

"I will not let one stubborn man stand in our way — I am committed to making this bill become law. With every new vote in the House and Senate, we come closer to a veto proof majority.

"The 2006 election was largely a referendum on President Bush's policies and the results make clear that his first veto was a mistake.

"As one of the major legislative agenda items of the newly elected Democratic Congress, the House again passed this with an even greater majority in January — of the 16 new Democratic votes in support, 14 were cast by members who defeated or replaced Republicans who opposed this research.

"With the House passage earlier this month, we picked up two more votes. We are making progress towards overriding the president's veto.

"The president can do this the hard way, or the easy way — unfortunately he has chosen the hard way. I will continue to give the president the opportunity to do the right thing."

Multiple Sclerosis Patients Benefit From High Dose, High Frequency Interferon Beta: Presented at ENS

By Thomas S. May

RHODES, GREECE -- June 20, 2007 -- Patients with relapsing-remitting multiple sclerosis (MS), the most common form of MS, derive greater benefit from interferon beta-1a when it is administered subcutaneously at a 44 mcg dose three times weekly than when it is given as a 30 mcg intramuscular injection once a week. This finding was announced here at the annual Meeting of the European Neurological Society (ENS), based on interim results of the Evidence of Interferon Dose-response: European North American Comparative Efficacy (EVIDENCE) trial.

"The EVIDENCE study was a head-to-head comparison of two important Interferon beta-1a products for MS, and it determined that there is a significant early and sustained benefit, both for clinical and MRI outcomes, from using a higher frequency and higher dose of interferon," said lead investigator Anthony Traboulsee, MD, clinical assistant professor, department of neurology, University of British Columbia Hospital, Vancouver, British Columbia, Canada. "The data presented here is an extension of the MRI results, specifically looking at T 2 burden of disease," Dr. Traboulsee added. "T 2 burden of disease represents the chronic accumulation of new and old MS lesions, and it was the first MRI measure approved by regulatory agencies for clinical trials."

The EVIDENCE trial compared T 2 burden of disease (BOD) between two groups of patients: subjects in one group (n=279) were given 44 mcg of Interferon beta-1a (IFN beta-1a) subcutaneously (sc) three times a week, while subjects in the other group (n=274) received 30 mcg of IFN beta-1a intramuscularly (im) once a week. The primary endpoint was percentage change in BOD over 48 weeks, and all patients with evaluable T 2 MRI scans at baseline and at week 48 were included in the analysis.

The investigators found that median percentage reduction in BOD from baseline to week 48 was greater in the 44 mcg sc treatment group than in the 30 mcg im group (–6.7 % [range –65, 431] versus –0.6 % [range –61, 197]). Median absolute reduction in BOD was also greater in the 44 mcg sc group (–189.5 mm3; range –23454, 56869) than the 30 mcg im group (–19.0 mm3; range –13337, 10161).

Based on these data, the investigators concluded that patients treated with 44 mcg of subcutaneous Interferon beta-1a three times per week had significantly greater reductions in T 2 burden of disease than those receiving 30 mcg intramuscular injections once a week. According to Dr. Traboulsee, "this study demonstrates the benefits of high dose, high frequency dosing on suppression T 2 BOD, and is consistent with previous results showing similar benefits on relapse rates."

Financial support for the EVIDENCE trial was provided by Merck Serono, the makers of Interferon beta-1a.


[Presentation title: Reduction in T2 Burden of Disease Is Greater With Interferon beta-1 a 44 mcg Administered Subcutaneously Three Times Weekly Than 30 mcg Administered Intramuscularly Once Weekly: 1-Year Analysis of the EVIDENCE Study Data. Abstract P539]

Opexa Therapeutics Reports Positive Top-line Data in Phase I/II Extension Trial with Tovaxin(TM) for Multiple Sclerosis

Jun 21 2007, 9:19 AM EST

Business Wire

Opexa Therapeutics, Inc. (NASDAQ:OPXA), a company involved in the development and commercialization of cell therapies, today announced positive top-line data in an open-label Phase I/II extension clinical trial of the investigational T-cell vaccine, Tovaxin(TM), for multiple sclerosis (MS). In this one-year, 8-subject extension clinical trial of relapsing remitting (RRMS) and secondary progressive (SPMS) subjects, Tovaxin therapy was shown to be safe and effective. The "per-protocol" analysis of Tovaxin therapy achieved a 92% reduction in annualized relapse rate (ARR) in subjects who received two treatment doses of 30 - 45 x 10(6) attenuated T-cells eight weeks apart and were monitored for an additional 44 weeks. Subjects in the extension study had previously been treated an average of 5.2+/-1.8 (1, 8; median 5.4) years earlier at Baylor College of Medicine under the direction of Jingwu Zhang, M.D., Ph.D with a T-cell vaccine developed from myelin basic protein (MBP) reactive T-cells. The safety profile revealed only injection site mild reactions and no severe adverse reactions related to T-cell vaccination.

Both Phase I/II clinical studies have demonstrated that T-cell vaccination depletes myelin reactive T-cells in peripheral blood. In the extension study patient population, the myelin reactive T-cell frequencies were reduced by 84% and 72% at 6 and 12 months on study, respectively. Reductions in myelin reactive T-cell frequencies in the dose escalation study were 76.7% and 64.8% at 6 and 12 months on study, respectively.

All subjects currently are enrolled in a retreatment extension study to collect longitudinal safety and effectiveness data.

Effectiveness data for the 13 RRMS subjects across the two Phase I/II trials showed an 80% reduction in ARR. The Expanded Disability Scoring Scale (EDSS) for the RRMS subjects for a 0.5 point effect was improved, unchanged and worsened by 64.3%, 21.4% and 14.3%, respectively. The EDSS for a 0.5 point sustained (no change over 3 months) effect was improved, unchanged and worsened by 42.9%, 42.9% and 14.2%, respectively. The EDSS for a 1.0 sustained effect was improved, unchanged and worsened by 28.6%, 57.1% and 14.3%, respectively.

Brian Loftus, M.D. of Bellaire Neurology, the Principal Investigator of these Tovaxin studies, commented, "This data, combined with prior data presented on myelin reactive T-cell frequencies and ARR reductions, laid the ground work for the placebo-controlled Tovaxin IIb clinical trial (TERMS). We have shown that myelin reactive T-cells can be identified and used to produce T-cell vaccine which effectively induces the depletion of an individual's autoreactive T-cells and results in positive clinical outcomes. I anticipate Tovaxin will usher in the age of personalized therapy for MS."

David McWilliams, president and chief executive officer of Opexa, said, "We are particularly encouraged by the data from this extension trial which indicates that subjects previously treated with T-cell vaccine can be safely and effectively retreated with Tovaxin. This outcome is important to our planned extension trial for subjects currently enrolled in our TERMS trial following the one year core study time period." In addition, the effectiveness data in RRMS subjects across the two Phase I/II trials indicate strongly positive outcomes in both ARR and EDSS improvements following Tovaxin therapy."

About TERMS

The Tovaxin Phase IIb clinical study will include 150 patients in a multicenter, randomized, double blind, placebo-controlled trial designed primarily to evaluate the efficacy, safety and tolerability of the Tovaxin T-cell vaccination with clinically isolated syndrome (CIS) and relapsing-remitting MS (RR-MS) patients. A total of 100 patients will receive Tovaxin, while 50 will receive placebo. The study is designed as a two-arm, 52-week, parallel-group study, whereby patients will be given five subcutaneous injections at 0, 4, 8, 12 and 24 weeks. The analyses will be performed at the end of the 52-week study to assess the safety and efficacy of Tovaxin. The primary efficacy variable is the cumulative number of gadolinium-enhancing lesions on T1-weighted MRI scans summed over the Week 28, 36, 44, and 52 MRIs. The secondary efficacy variables are the cumulative number of new gadolinium-enhancing lesions at Weeks 28-52, the change in T2-weighted lesion volume, and the annualized relapse rate. As of May 17, 2007, Opexa announced the completion of patient enrollment in a 150-patient Phase IIb safety and efficacy study (TERMS). All patients who complete the trial will be eligible to participate in an optional one-year extension study, in which they will receive Tovaxin under an open-label protocol. The open-label study is being planned under a different protocol that will be submitted to the FDA.

The TERMS study is being conducted at 36 U.S. sites to evaluate the safety and effectiveness of Tovaxin. The TERMS study is registered on the U.S. National Institutes of Health-sponsored website, www.clinicaltrials.gov, where pharmaceutical companies are required to register trials for medicines that will treat serious or life-threatening diseases or conditions. For more information, visit the TERMS website at www.tovaxin.com.

About T-cell Vaccination

For a T-cell vaccine to be effective, it should be able to induce T-cell cytotoxic and/or regulatory immune responses against the pathogenic T-cells. Studies of T-cell vaccine have indicated that T-cell vaccination with peripheral blood-derived autologous myelin-peptide selected T-cells in multiple sclerosis patients resulted in the in vivo induction of CD8+ cytotoxic T-cells and CD4+CD25+FoxP3 Tregs specific for T-cell vaccine. The induction of anti-idiotypic cytotoxic CD8+ effector T-cells and anti-ergotypic CD4+CD25+FoxP3 positive Tregs is believed to provide a therapeutically effective dual mechanism of protection to patients treated with Tovaxin(TM). The observed regulatory immune responses have been shown to collectively correlate with clinical improvement in treated patients.

About Opexa Therapeutics

Opexa Therapeutics develops and commercializes cell therapies to treat autoimmune diseases such as MS, rheumatoid arthritis, and diabetes. The Company is focused on autologous cellular therapy applications of its proprietary T-cell and stem cell therapies. The Company's lead product, Tovaxin(TM), a T-cell therapy for multiple sclerosis is in a Phase IIb trial. The Company holds the exclusive worldwide license for adult multipotent stem cells derived from mononuclear cells of peripheral blood. The technology allows large quantities of monocyte derived stem cells to be produced efficiently for use in autologous therapy, thus circumventing the threat of rejection. The Company is in preclinical development for diabetes mellitus. For more information, visit the Opexa Therapeutics website at www.opexatherapeutics.com.

Safe Harbor Statement

This press release contains "forward-looking statements," including statements about Opexa Therapeutics' growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. These forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Opexa Therapeutics' ability to obtain additional funding, develop its stem cell technologies, achieve its operational objectives, and obtain patent protection for its discoveries, that may cause Opexa Therapeutics' actual results to be materially different from any future results expressed or implied by such forward-looking statements. Opexa Therapeutics undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

Multiple Sclerosis Patients' Response to Interferon Beta Predicted by MRI: Presented at ENS

By Thomas S. May

RHODES, GREECE -- June 19, 2007 -- Magnetic resonance imaging (MRI) of brain lesions at the beginning and after one year of treatment with Interferon beta (IFN-b) can help identify patients with multiple sclerosis (MS) who do not respond to IFN-b treatment, according to a study presented here at the 17th Meeting of the European Neurological Society (ENS).

"Early identification of nonresponders may help neurologists in their decision about MS treatment," said Carlo Pozzilli, MD, Multiple Sclerosis Centre, S. Andrea Hospital, Rome, Italy. Dr. Pozzilli is head of the research team that performed the retrospective, post-marketing study involving 345 patients (101 men and 244 women, mean age at baseline 32.9±9.1 years) who had been treated with IFN-b for an average of 4.5 years (median 4, range 2-13). At the beginning of the study, subjects had a mean disease duration of 5.5±4.9 years and a median Expanded Disability Status Scale (EDSS) score of 1.5 (range 0-4.5).

The researchers analysed EDSS scores and MRI scans taken at baseline and after one year of IFN-b treatment of all patients who completed the study. For subjects who discontinued IFN-b therapy, the final EDSS score was calculated at the last neurological assessment during IFN-b treatment.

Patients with an increase of at least 1 point on the EDSS score (confirmed in two consecutive visits separated by a 6-month interval) were considered to have a "poor clinical response." Disease activity was determined based on the presence of gandolinium-enhancing (Gd-enhancing) lesions in post-contrast T1-weighted scans and on the accumulation of hyperintense lesions on T2-weighted images.

Patients with a longer disease duration at the beginning of IFN-b treatment and a higher baseline EDSS than those with a stable level of disability were also more likely to have a poor response to IFN-b therapy (P =.04 and P <.001, respectively). A relapse within the first year of IFN-b therapy also was associated with an increased likelihood of poor response over the study period (OR 2, 95% CI 1.3-3.4; P =.003)

The investigators found, however, that MRI data were even stronger predictors of long-term outcome, whereby both the presence of at least one Gd-enhancing lesion at 1-year (OR 3.4, 95% CI 2-5.7; P <.001) and an increase in T2 lesion burden (OR 8.6, 95% CI 5-14.5; P <.001) were related to a poor outcome.

According to Dr. Pozzilli, "these results underline the importance of performing an MRI scan at the end of the first year of treatment with Interferon beta, in order to identify patients who do not respond to treatment."


[Presentation title: Early Predictors of Poor Response to Interferon Beta Therapy in a Cohort of Relapsing-remitting Multiple Sclerosis. Abstract P294]

Depression Not Related to Disease Modifying Therapy in Multiple Sclerosis: Presented at ENS

By Thomas S. May

RHODES, GREECE -- June 19, 2007 -- Patients with multiple sclerosis (MS) often become depressed, and it is commonly believed that the depression is related to disease modifying treatment (DMT) with Interferon-beta. However, the results of a new study presented here at the 17th Meeting of the European Neurological Society (ENS) contradict this notion.

The study was performed by Stephen Kirzinger, MD, assistant professor, University of Louisville School of Medicine, Louisville, Kentucky, United States, and colleagues, and it involved a retrospective chart review of 112 patients with MS who had been treated either with Interferon-beta or with Glatiramer Acetate (GA) for up to 48 months.

To determine the relationship between DMT and depressive symptoms, patients were evaluated for depression using the Beck Depression Inventory (BDI) at baseline (within 6 weeks of initiating a DMT) and at each subsequent visit. In addition, patients' response to DMT was also evaluated using various measures such as the Expanded Disability Status Scale (EDSS), Modified Fatigue Impact Scale (MFIS), and the CogniStat (to assess cognitive impairment).

To be included in the study, patients must have completed a BDI within 6 weeks of starting their DMT. Sixty-seven subjects fulfilled this criterion and were included in the analysis. Forty-two had been exclusively on Interferon-beta and 25 received GA therapy.

An analysis of the results revealed no statistically significant difference between the two treatment groups with respect to the presence of depression, the investigators reported. They also noted that treatment with antidepressant medication did not significantly alter the results. Patients on Interferon-beta had a mean BDI score of 12.3 (SD=8), whereas patients treated with GA had a mean score of 12.1 (SD=7.7).

These findings do not support the common perception that disease modifying therapy with Interferon-beta is associated with depressive symptoms, the researchers concluded.


[Presentation title: Depression: Relationship to Disease-modifying Therapy. Abstract P284]

Positive Results Published On Testosterone For Men With MS

Researchers from the University of California, Los Angeles have published results from a small study, funded by the National MS Society and others, suggesting that one year of treatment with a gel containing the sex hormone testosterone (applied to the skin) in 10 men with relapsing-remitting multiple sclerosis resulted in significant improvements in cognitive function and in slowing brain tissue loss. Nancy Sicotte, MD, Rhonda Voskuhl, MD, and colleagues report these positive findings in the May 2007 issue of Archives of Neurology (2007;64:683-688 ).

Further research involving larger numbers of patients and controls would help to confirm and expand these early results, and to ensure the safety and effectiveness of testosterone treatment in MS.

Background: Sex hormones may contribute to MS susceptibility by influencing the immune attack on brain and spinal cord tissues. Laboratory studies have shown that the severity of EAE, an MS-like disease, is decreased when testosterone, a male sex hormone, is administered to male and female mice. Dr. Voskuhl was awarded funding from the National MS Society's targeted research initiative on Gender Differences in MS to undertake a small study of testosterone gel in men with MS. Preliminary results of this study were originally presented at the 58th Annual Meeting of the American Academy of Neurology in April 2006.

Study: Ten men with relapsing-remitting MS, ranging from 29 to 61 years of age, were studied. Relapsing-remitting MS is the most common form of the disease, involving clearly defined flare-ups followed by partial or complete recovery periods. After a six-month observation period, they were treated with testosterone gel applied to the skin (10 grams daily, containing 100 mgs of testosterone) for one year. None of the men were taking disease-modifying therapies. Clinical assessments including blood tests, as well as clinical measures of disease activity and cognitive function were completed every three months. Magnetic resonance imaging scans were taken before treatment and monthly to measure evidence of disease activity. The extent of brain tissue loss (atrophy) was assessed by determining normalized brain volumes using automated computer software.

Since all 10 of the men received treatment and none received inactive placebo, the investigators compared measures taken before treatment versus after treatment. Testosterone levels were in the lower range of normal before treatment, and although they increased with treatment, remained in the normal range.

After 12 months of testosterone treatment, measures of clinical disease activity remained stable, blood tests were normal, and no adverse events related to treatment were reported. The men showed significant improvements in performance on a test of cognitive function called the Paced Auditory Serial Addition Task (a test of processing speed and memory) compared to the pre-treatment period. The authors report that the improvement could not be accounted for by well-known "practice effects," which had stabilized during the pre-treatment period.

MRI scans showed no increases in disease activity or tissue damage during treatment, although the authors note that the patients began the study with relatively low levels of disease activity on MRI.

Significantly, the rates of brain atrophy, measured by normalized brain volume, slowed by 67 percent during the last nine months of treatment. Muscle mass increased significantly during the study; testosterone is sometimes used for this purpose in other chronic diseases.

This small study shows that testosterone treatment may have therapeutic benefit in men with relapsing-remitting MS. Further study involving larger numbers of patients and control groups is necessary to confirm these early results, and to ensure the safety and effectiveness of testosterone treatment for MS.

"We're gratified that these early, promising results stemmed from the National MS Society's targeting of gender differences as an important area of research in MS," said Dr. John R. Richert, the Society's executive vice president of research. "It also demonstrates how basic laboratory findings can quickly translate into possible new therapeutic strategies."

Dr. Voskuhl and colleagues are already proceeding with a similar effort involving the sex hormone estriol: Based on a small, early-phase trial that showed decreases in disease activity in 12 women with MS, she is now launching a multicenter, controlled clinical trial of oral estriol (added to the approved MS therapy glatiramer acetate) in 130 women with relapsing-remitting MS.

Stem Cell Bill Passes MS, Activists Attend Event At U.S. Capitol - Stem Cell Bill Moves To President's Desk

The House of Representatives passed the Stem Cell Research Enhancement Act (S. 5) on Thursday, June 7, with a bipartisan vote of 247 to 176. Thank you to the thousands of you who contacted your representatives in Congress recently in support of this issue. Several MS activists participated in an event lauding the passage of the bill in the U.S. Capitol building following the vote. They joined Speaker of the House Nancy Pelosi (CA) and Senate Majority Leader Harry Reid (NV), along with House champions Mike Castle (DE) and Dianne DeGette (CO) and Senate champions Dick Durbin (IL) and Arlen Specter (PA), at the celebration.

MS activists who joined in the event included Janet Abrams, Yvonne Brown, Sharon Dodge, Rob Engel, Karen Jackson, Philip Fryer, David Powell, and Bev Thomas. MS activists nationwide have been leaders in speaking out in support of expanded stem cell research.

The bill is now on its way to the president's desk, but he has vowed to veto any legislation lifting his ban on federal funding for additional embryonic stem cell lines. At the Administration's request, this bill includes language that encourages the National Institutes of Health (NIH) to pursue other forms of stem cell research outside embryonic stem cell research. It is because of this modification that the House needed to vote on the Senate bill (S. 5). However, it is expected that President Bush still will veto the bill.

If a veto occurs, the bill will return to the Congressional chamber of origin- in this case the Senate- for an override attempt. A two-thirds majority is necessary to override a presidential veto. While the votes are close, it is possible that the Senate will have the 67 votes necessary. We will keep all MS activists up to date as this progresses in the coming week.

Recent News on Stem Cell Research

The Society is encouraged by recent news on other scientific advances related to stem cells, such as "reprogramming" stem cells without destruction of the embryo. The Society hopes that this science can be verified through peer review studies. We continue to support all types of stem cell research that could help end the devastating effects of MS.

Autoimmune Disease Rally and Health Fair

MS activists participated in the Autoimmune Disease Awareness Rally and Health Fair on May 22, in recognition of May 2007 as National Autoimmune Diseases Awareness Month. The American Autoimmune Related Diseases Association (AARDA) and the National Coalition of Autoimmune Patient Groups (NCAPG) hosted, and the Society helped sponsor and support, this important event.

Congressmen Steve Israel (NY) and Patrick Kennedy (RI) spoke at the rally, highlighting the need for better education, research, and understanding of autoimmune diseases. Dave Gearing, who lives with MS , spoke to the need for better diagnostic tools and imaging for identifying autoimmune diseases. The event helped call on Americans to learn more about autoimmune diseases like MS, which are still not well-known or understood by the medical and research communities and the public.

Defense Appropriation for MS Research

The House Defense Appropriations Subcommittee currently is considering the $15 million federal appropriation for multiple sclerosis (MS) research. The issue continues to move forward in Congress but will likely wrap up by mid-July. MS activists whose legislators have particular influence over this issue have been taking action recently.

Recent studies of U.S. veterans living with MS indicate the need for additional research through this Defense appropriation. Read the story of a Gulf War veteran in Kentucky who is living with MS. The funding would be appropriated through the Office of Congressionally Directed Medical Research Programs (CDMRP), administered by the Department of Defense, for research into the triggers and treatments of MS. This new source of federal funding for MS research could help move us closer to a world free of MS.

National Multiple Sclerosis Society

Genzyme and Bayer HealthCare Announce Detailed Interim Two-Year Alemtuzumab in Multiple Sclerosis Data Presented at AAN

Interim analysis of Phase 2 comparative study showed significant results in favor of alemtuzumab versus Rebif®

CAMBRIDGE, Mass. and Wayne, NJ - Genzyme Corporation (Nasdaq: GENZ) and Bayer HealthCare Pharmaceutical today announced detailed interim results from the CAMMS223 Phase 2 study. This interim analysis of all patient data through at least twenty-four months from the start of the study for all patients showed that a once-yearly cycle of alemtuzumab treatment had a statistically significant impact on reducing the frequency of relapses and the sustained accumulation of disability in early active relapsing remitting multiple sclerosis (RRMS) patients compared to Rebif® (interferon beta-1a).

The data were presented yesterday at the 59th Annual Meeting of the American Academy of Neurology (AAN) in Boston by Dr. Alasdair J. Coles, Ph.D., MRCP, Addenbrooke's Hospital, University of Cambridge, United Kingdom. This is the first time that an analysis of the primary and secondary endpoints has been presented in full.

Dr. Coles' presentation showed patients taking alemtuzumab at the high dose experienced an 87 percent reduction in the risk for relapse (p<0.0001) and a 66 percent reduction in the risk for progression of clinically significant disability (p<0.0098) when compared to patients treated with Rebif. At the low dose, patients taking alemtuzumab experienced similar results, with a 72 percent reduction in the risk for relapse (p<0.0001) and an 88 percent reduction in the risk for progression of clinically significant disability (p<0.0008) compared with patients treated with Rebif. Patients in both alemtuzumab arms also achieved a statistically significant reduction in disability compared with their pre-treatment baseline, as measured by their Extended Disability Status Scale (EDSS) scores.

"Although several therapies are already available to treat MS, patients still face an unmet need for more effective treatment that further stabilizes disability," said Principal Investigator Professor D. Alastair S. Compston, MBBS, Ph.D., FRCP, FMedSci, Addenbrooke's Hospital, University of Cambridge, United Kingdom. "The large two-year reductions in the risk of relapse and sustained accumulation of disability seen in these interim results are impressive, and potentially very encouraging for the many people worldwide who currently face an uncertain future with this devastating disease and for their treating physicians."

As previously announced, dosing of alemtuzumab in this study was voluntarily suspended in September 2005 after three cases of immune thrombocytopenic purpura (ITP) were reported, the first of which resulted in a fatality. The U.S. Food and Drug Administration (FDA) subsequently placed the study on clinical hold. To date, six of the 216 (2.8 percent) alemtuzumab-treated patients in the CAMMS223 study have developed ITP. ITP is a disorder characterized by a low platelet count and corresponding increased risk of uncontrolled bleeding. Though potentially serious, ITP can be detected and monitored through blood tests, and is usually treatable.

At the time of the dosing suspension, most patients had received two cycles of therapy with alemtuzumab. Treatment with Rebif in the control arm continued without interruption. Alemtuzumab re-dosing in the trial remains on clinical hold in the United States, and active discussions are underway with regulatory authorities regarding the clinical development program. Significant progress has been made toward the initiation of two planned Phase 3 clinical trials, one that will include previously untreated patients and one that will involve patients receiving an approved therapy whose disease remains active. These Phase 3 studies are expected to begin this year, following FDA clearance. Alemtuzumab is an investigational drug for the treatment of MS. Alemtuzumab should not be used in MS outside of the formal clinical trial setting so that patient safety, including the risk of ITP, can be monitored.

Phase 2 Study Details

The open-label, rater-blinded, randomized study enrolled 334 treatment-naïve patients with early, active, RRMS. The trial compares the safety and efficacy of alemtuzumab to Rebif. This is the first time that a potential new therapy for multiple sclerosis has undergone a prospective, controlled, multi-year, head-to-head comparison to a recommended first-line therapy.

In the trial, patients with RRMS at 49 medical centers in Europe and in the U.S. were treated with alemtuzumab at one of two doses (12 or 24 mg IV per day for five days at initial treatment, and for three days in the subsequent yearly treatments), or Rebif (44 mcg administered subcutaneously three times per week, as indicated in its product label). Although treating physicians were aware of which treatment patients received, independent (blinded) neurologists assessed the disability efficacy endpoint and performed relapse evaluations.

Primary endpoints in the trial were the annualized relapse rate and the time to Sustained Accumulation of Disability as measured by an increase in EDSS scores lasting at least six months. The efficacy and safety data analyses were reviewed by an independent Data and Safety Monitoring Board. The final analysis of the primary endpoints in CAMMS223 will be based on data through three years in all patients.

In addition to the results of the co-primary endpoints outlined above, Dr. Coles presented the interim results of the change from baseline in MRI T2 lesion volume and mean EDSS, which are secondary and tertiary endpoints, respectively. Each of these findings supports the results seen in the primary endpoints.

Safety Results

In the comparison of safety parameters of alemtuzumab vs. Rebif, a greater number of serious adverse events (a subset of total adverse events) were reported in patients receiving Rebif than in the two alemtuzumab dose groups combined. Most of these were associated with patients who were hospitalized for treatment of their MS.

The majority of adverse events (93 percent) in all three arms, including infusion-associated adverse events, were mild-to-moderate in intensity. The total number of adverse events was approximately twice as high in each of the alemtuzumab-treated arms as in the Rebif-treated arm, primarily due to the high number of infusion-associated adverse events. Excluding infusion-associated adverse events (i.e., those occurring within 48 hours of an infusion), the incidence of adverse events was similar across the three arms.

To date, a total of six of 216 (2.8 percent) alemtuzumab-treated patients in the CAMMS223 study have developed ITP. In the initial case, symptoms of ITP were experienced but not recognized in time to seek prompt medical attention. After that case, the sponsor notified investigators and patients of the risk of ITP, and a Patient Monitoring Program for ITP was implemented in CAMMS223. The other five ITP patients were diagnosed promptly, responded well to medical treatment, and have been stable without ongoing treatment for ITP for between five and thirteen months. No new cases of ITP have been reported in the study since September 2006. A presentation of updated ITP information will be made at the AAN conference by Herman Sullivan, MD on Wednesday, May 2, at 4:30PM EDT.

Additionally, the proportion of patients with thyroid-related clinical adverse events after alemtuzumab treatment was 16.2 percent vs. 1.9 percent after Rebif treatment. Thyroid adverse experiences were substantially less common in the two years after alemtuzumab treatment than in prior studies of the product in MS patients. A poster presentation of updated thyroid autoimmunity information will be made by Dr. Coles on Thursday, May 3.

About Multiple Sclerosis

Multiple sclerosis is an immune-mediated disease of the central nervous system (CNS) in which the immune system may attack the brain and spinal cord. MS affects approximately 2.5 million people worldwide and approximately twice as many women as men. The clinical course of MS is highly variable, but is typically characterized by an initial relapsing and remitting phase where episodes of transient neurological compromise are followed by partial to full recovery. Within 10 to 20 years, however, most patients experience progressive disability in which a steady worsening of symptoms may culminate in profound muscle weakness, impaired gait and mobility, bladder and bowel dysfunction, and cognitive and visual impairments. At onset, relapsing-remitting MS is the most common form of this disease.

About Alemtuzumab

Genzyme is conducting the clinical development program of alemtuzumab in multiple sclerosis. Bayer HealthCare holds exclusive worldwide marketing and distribution rights to alemtuzumab and participates with Genzyme in the design of clinical protocols and conduct of activities for the development of alemtuzumab for the treatment of MS.

Alemtuzumab is an investigational drug for the treatment of MS, and should not be used outside of the formal clinical trial setting.

Alemtuzumab was approved in 2001 and is marketed outside the United States as MabCampath®and in the U.S. by Bayer HealthCare Pharmaceuticals Inc., as Campath®. The product is indicated for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Determination of the effectiveness of Campath is based on overall response rates. Comparative, randomized trials demonstrating increased survival or clinical benefit such as improvement in disease-related symptoms have not yet been conducted.

Alemtuzumab is a humanized monoclonal antibody that binds to a specific target, CD52, on some cells of the immune system, including lymphocytes. When alemtuzumab binds to these cells, it triggers their destruction by the immune system. It is the first and only monoclonal antibody approved by the FDA for the treatment of patients with B-cell Chronic Lymphocytic Leukemia (B-CLL), a malignant disease of B-lymphocytes.

Campath should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. Campath has a boxed warning which includes events of hematologic toxicity, infusion reactions, and infections/opportunistic infections.

Campath is contraindicated in patients who have active systemic infections, underlying immunodeficiency (e.g., seropositive for HIV), or known Type 1 hypersensitivity or anaphylactic reactions to Campath or to any one of its components.

The most commonly reported infusion-related adverse events in patients with B-CLL were rigors, drug-related fever, nausea, vomiting, and hypotension. Hematologic toxicities included pancytopenia/marrow hypoplasia, anemia, thrombocytopenia, neutropenia, and profound lymphopenia, and should be monitored. Infections reported included sepsis, pneumonia, and opportunistic infections such as CMV, candidiasis, aspergillosis, and mucormycosis.

Please refer to www.campath.com for complete prescribing information of Campath in CLL.

About Genzyme

One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 9,000 employees in locations spanning the globe and 2006 revenues of $3.2 billion. Genzyme has been selected by FORTUNE as one of the "100 Best Companies to Work for" in the United States.

With many established products and services helping patients in nearly 90 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune diseases, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as immune disease, infectious disease, and other areas of unmet medical need.

About Bayer HealthCare

Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals unit of Bayer HealthCare LLC, a division of Bayer AG. One of the world's leading, innovative companies in the healthcare and medical products industry, Bayer HealthCare combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the US, Bayer HealthCare Pharmaceuticals comprises the following business units: Women's Healthcare, Diagnostic Imaging, Specialized Therapeutics, Hematology/Cardiology and Oncology. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

Forward-Looking Statements

This press release contains forward-looking statements, including statements about clinical trial results, regulatory plans and expected timelines for alemtuzumab, including the initiation of a Phase 3 trial in MS patients and the timing thereof, and the ability to manage patient safety. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others: that final results of the clinical trial demonstrate safety and efficacy comparable to the interim data that have emerged to date, the actual timing and content of submissions to and decisions made by the regulatory authorities, institutional review boards, data safety monitoring boards and treating physicians regarding the continued administration of alemtuzumab to MS patients, Genzyme's ability to develop and obtain approval of a patient safety plan, and the other risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission.

Please see the disclosure under the heading "Risk Factors" in the Management's Discussion and Analysis of Genzyme Corporation and Subsidiaries' Financial Condition and Results of Operations section of Genzyme's Annual Report on Form 10-K for the year ended December 31, 2006 for a more complete discussion of these and other risks. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise the statements.

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

Genzyme®, Campath®, and MabCampath® are registered trademarks of Genzyme Corporation. All rights reserved.

Rebif® is a registered trademark of EMD Serono, Inc.

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Genzyme's press releases and other company information are available at www.genzyme.com and by calling Genzyme's investor information line at 1-800-905-4369 within the United States or 1-703-797-1866 outside the United States.

Bayer HealthCare press releases and other information are available at pharma.bayer.com or by calling 1-888-84BAYER.