A shameful indictment
By Bernard Purcell
Wednesday May 30 2007
IRELAND has some of the most inadequate provision for care of people with Multiple Sclerosis in Europe, a conference heard yesterday.
MS is the most widespread neurological disease in the world today, with an estimated 2,500,000 people suffering damage to their central nervous systems.
Across Europe, 500,000 people have been diagnosed with MS. The causes are not yet known but the symptoms include blurred vision, weak limbs, spasms, tingling sensations, slowed speech and fatigue.
A major specialist conference in Brussels - the European Multiple Sclerosis Platform - sponsored by the European Parliament and German EU Presidency, yesterday cited Ireland as one of the most unequal countries for supporting people with the illness - alongside Poland where just 1pc of MS patients are treated with essential drugs.
Ireland has just 16 competent neurologists - and five neurological units and two rehab centres - to cater to 10,000 MS sufferers. Iceland has 18 neurologists for just 330 MS patients while Finland, on the other hand, has 40 units for 7,000 MS patients.
Even Romania, one of the poorest countries in the EU, has 72 units for 10,000 patients.
But experts fear Romania - along with Bosnia-Herzegovina, Croatia and Latvia - may well be under-reporting or failing to diagnose the illness as incidences of it are very low for countries of their size.
Sweden has 14,000 MS sufferers and 400 neurologists, while the Czech Republic, with 13,000 sufferers, has 335 neurologists.
Several EU countries, but not Ireland or Britain, have a dedicated pension fund for MS sufferers.
- Bernard Purcell
Wednesday, May 30, 2007
By Pete Mansell
29/05/2007 - Suppressing granulocyte macrophage colony-stimulating factor (GM-CSF) to tackle inflammatory and autoimmune diseases is the concept behind a new worldwide collaboration between German-American biopharmaceutical company Micromet and Denmark's Nycomed.
The agreement centres on Micromet's MT203, a human antibody expected to enter clinical trials in 2008. According to the new partners, MT203 neutralises GM-CSF, a cytokine known to play a significant role in autoimmune and inflammatory disease. Preclinical studies conducted by Micromet make a case for developing MT203 as a treatment for rheumatoid arthritis, multiple sclerosis, psoriasis, asthma and chronic obstructive pulmonary disease, they say.
Under the collaboration, Micromet will receive an upfront licence fee of €5m and additional payments and research and development (R&D) reimbursements of more than €120m in aggregate on achieving development milestones. The company is also eligible for royalties on worldwide sales of MT203 and any other products that may emerge from the agreement.
Micromet will take most of the responsibility for preclinical testing, process development and manufacturing of MT203 for early clinical trials, while Nycomed will be responsible for clinical development and commercialisation worldwide. Nycomed will also bear the cost of development activities and will reimburse Micromet for any expenses incurred in connection with the development programme.
Neutralising GM-CSF "presents a new biology concept in inflammatory processes and may have the potential to improve the lives of patients suffering from severe chronic inflammatory and autoimmune diseases," said Anders Ullman, Nycomed's executive vice-president R&D.
A human, high-affinity IgG1 antibody, MT203 was generated by Micromet using phage display-guided selection. The results of in vitro studies published last May in the journal Molecular Immunology showed that MT203 bound with picomolar affinity to an epitope on human and macaque GM-CSF involved in high-affinity receptor interaction.
As a consequence, the Micromet researchers said, the antibody potently prevented both GM-CSF-induced proliferation of TF-1 cells (these are used in proliferation bioassays for a number of cytokines and neutralising antibodies) and production of the chemokine IL-8 by U937 cells. MT203 significantly reduced both the survival and activation of peripheral human eosinophils, "as may be required for effective treatment of inflammatory lung diseases," they noted.
Another encouraging finding was that the antibody did not show any detectable loss of neutralising activity after five days in human serum at a temperature of 37°C.
In late June 2006, Micromet reported results from a study in arthritic mice challenged with streptococcus cell-wall fragments, in which a GM-CSF neutralising monoclonal was compared with the TNF (tumour necrosis factor)-alpha blocker etanercept, sold by Wyeth as Enbrel.
The monoclonal antibody (mAb) was found to be more potent than etanercept at reducing swelling of affected knee joints. While both the mAb and etanercept decreased the number of inflammatory cells in the joints, only the mAb cut levels of interleukin-1 beta (IL-1 beta) and reduced proteoglycan loss from the articular knee cartilage, Micromet pointed out.
IL1-beta mediates cartilage and bone destruction via secretion of metalloproteinases and decreases the synthesis of proteoglycan, one of the main components of the articular cartilage that cushions the body's joints.
These results suggested, therefore, that antibody neutralisation of GM-CSF might not only reduce inflammation but also protect cartilage from the destruction characteristic of arthritis - and that it might do so in TNF-alpha independent disease.
For Nycomed, the deal on MT203 highlights the company's strategic interest in inflammatory research and is the first example of its "strong commitment" to external collaborations at all stages of drug development as a key component of a new R&D strategy.
Following its acquisition of Germany's Altana Pharma in September 2006, Nycomed announced details earlier this year of an integration programme and strategic realignment that included redefining its R&D model to make it more flexible, results-oriented and "able to forge strong partnerships with external partners."
Tuesday, May 29, 2007
DUBLIN, Ireland -- Elan Corp. and Biogen Idec Inc., co-makers of Tysabri, announced Tuesday that U.S. regulators soon would review the drug for its possible use by sufferers of the gastrointestinal Crohn's disease.
Both companies said two review committees of the U.S. Food and Drug Administration would jointly consider July 31 whether to permit sale of Tysabri to treat Crohn's, which causes chronic but nonfatal inflammation of the intestines and afflicts one million people world-wide.
Clinical trials of Tysabri -- which last year was approved for use in the United States and European Union to combat the most advanced cases of multiple sclerosis _ have indicated that the drug is effective in preventing inflammatory immune cells from penetrating the wall of the intestine, limiting the damage they can cause.
Tysabri's use for MS patients has been heavily restricted because of its link to a rare, usually fatal disease of the central nervous system called progressive multifocal leukoencephalopathy, or PML. Both companies temporarily withdrew the drug from sale in February 2005 after three patients in clinical trials contracted PML; two, including a Crohn's sufferer, died.
Elan of Dublin, Ireland, and Biogen Idec of Cambridge, Mass., in December applied for FDA approval of Tysabri for Crohn's sufferers.
The disease most commonly develops in people in their teens and 20s and has no cure. It can cause diarrhea, abdominal cramps, fever and bowel obstructions, leading to lost appetite and weight.
The leading current treatment for Crohn's is Remicade, manufactured by Johnson & Johnson. Analysts say, if given FDA approval, Tysabri probably would be prescribed only to those Crohn's sufferers who were not responding to treatment from longer-established, lower-risk drugs.
Copyright © 2007 Associated Press
Friday, May 25, 2007
Acorda Therapeutics Presents Data from its Phase 3 Study of Fampridine-SR in Multiple Sclerosis at the American Academy of Neurology Meeting
BOSTON--(BUSINESS WIRE)--May 2, 2007--Acorda Therapeutics, Inc.® (Nasdaq: ACOR) today presented data from a Phase 3 clinical trial of Fampridine-SR in people with multiple sclerosis (MS) at the American Academy of Neurology meeting. Andrew Goodman, M.D., Director of the Multiple Sclerosis Center at the University of Rochester, presented top-line results on walking ability, leg strength, spasticity and clinician and subject global impressions. Dr. Goodman also presented a review of safety data.
The prospectively-designed analysis plan for the study was based on a responder criterion, defined as a consistent improvement in walking speed, as measured with the Timed 25 Foot Walk. A significantly greater proportion of people taking Fampridine-SR were Timed Walk Responders compared to people taking placebo (34.8 percent vs. 8.3 percent, p less than 0.0001). Increased response rate with treatment was seen across all four major (relapsing and progressive) types of MS.
The mean increase in walking speed, compared to pre-treatment, for Fampridine-SR treated Timed Walk Responders was significantly greater at every visit during the treatment period, compared to both Fampridine-SR Timed Walk Non-Responders and placebo treated patients (p less than 0.0001). The average increase in walking speed over the treatment period, compared to baseline, was 25.2 percent for the drug treated Timed Walk Responders vs. 4.7 percent for the placebo group. In follow-up visits, at two and four weeks after the end of the treatment period, Responder and Non-responder groups returned to their baseline walking speeds.
The clinical significance of the consistent response on the timed walk was validated in the trial primarily by the 12-Item Multiple Sclerosis Walking Scale (MSWS-12), a patient self-assessment of walking disability. There was a statistically significant improvement in the MSWS-12 score for walking Responders compared to Non-responders (p less than 0.001). In addition, the mean scores on all 12 questions in the MSWS-12 were better for the Responder group than the Non-responder group.
Subject Global Impression and Clinician Global Impression scales were used as secondary validators of clinical meaningfulness. Both measures also showed statistically significant improvement among Responders compared to Non-responders (p = 0.0010 and p less than 0.0001, respectively).
Statistically significant increases in leg strength, as measured by the Lower Extremity Manual Muscle Test (LEMMT), were seen in both the drug-treated Timed Walk Responders (p = 0.0002) and the drug-treated Non-responders (p = 0.046), compared to placebo-treated patients.
In an unplanned, direct comparison of Fampridine-SR vs. placebo-treated groups, the following measures were significantly improved in the Fampridine-SR-treated group: mean change in walking speed (p = 0.0004), mean change in the Lower Extremity Manual Muscle Test (p = 0.0029), and mean change in the Ashworth score for spasticity (p = 0.021).
Andrew Blight, Ph.D, Chief Scientific Officer of Acorda Therapeutics, commented, "Walking impairment is one of the most pervasive and serious disabilities afflicting people with MS, and there are no currently approved therapies that are indicated to improve walking in this population. Fampridine-SR, if approved, may offer a novel treatment for improving walking ability in people with MS, one that may be complementary to currently available therapies. In this study, we also saw improvements in measures of leg strength and spasticity compared to the placebo group. In particular, even the Fampridine-SR group that did not show a consistent walking improvement still showed a statistically significant improvement in leg strength compared to the placebo group. Further clinical studies would be required to determine whether such additional improvements may be clinically significant."
Study discontinuations due to adverse events occurred in 11 (4.8%) of the 229 Fampridine-SR-treated patients, and none of the 72 patient placebo group. Three of these events were considered serious: influenza, sepsis and anxiety. The anxiety was considered probably related to treatment. A focal seizure, observed during the sepsis, was considered possibly related to treatment. An additional 13 patients in the Fampridine-SR-treated group experienced various serious adverse events but none of these led to discontinuation from treatment and none was considered related to treatment. Most non-serious adverse events were rated as mild to moderate in intensity and observed at similar rates in Fampridine-SR and placebo groups. Some events were seen more frequently in the Fampridine-SR group (insomnia, fatigue, back pain, balance disorder) while upper respiratory infection was more common in the placebo group. Overall, the safety data were consistent with previous experience.
The double-blind, placebo-controlled trial was designed to evaluate the safety and efficacy of Fampridine-SR in improving walking ability in people with MS. The trial, which enrolled 301 individuals at 33 MS centers in the United States and Canada, recruited patients between 18 and 70 years old with a definite diagnosis of MS and some degree of walking disability. The study was open to people with all types of MS, including primary-progressive, secondary-progressive, relapsing-remitting and progressive-relapsing. Participants were permitted to remain on a stable regimen of their current medications, including immunomodulators. Secondary endpoints for the trial included the Lower Extremity Manual Muscle Test, the Ashworth Score for spasticity, and Subject and Clinician Global Impressions. Subjects were randomized to 14 weeks of treatment with Fampridine-SR (n=229) or placebo (n=72), a 3:1 ratio of drug to placebo. The safety measures in this trial included a physical examination and vital signs at each study visit, ECG, laboratory tests, and tests of drug plasma concentration in addition to adverse event monitoring.
Key inclusion criteria for the study included the ability to complete the Timed 25 Foot Walk twice at screening with times averaging between 8 and 45 seconds, having a confirmed diagnosis of MS and having a stable condition. Key exclusion criteria included a history of seizures, having previous treatment with fampridine or having an MS exacerbation within 60 days of screening.
Multiple sclerosis is a chronic, usually progressive disease of the central nervous system in which the immune system attacks and destroys the structure, and therefore degrades the function, of nerve cells. Approximately 400,000 Americans have MS, and every week about 200 people are newly diagnosed. Most are between the ages of 20 and 50, and women are affected two to three times as much as men. Worldwide, MS may affect 2.5 million individuals.
Over time, MS tends to lead to increasing disabilities such as walking impairment, muscle weakness, problems with cognition, speech or vision impairments. Approximately 80 percent of people with MS experience some form of walking disability. Within 15 years of an MS diagnosis, 50 percent of patients often require assistance walking and in later stages, about a third of patients are unable to walk. These complications may make it harder for people to work and may interfere with their ability to perform common, daily activities.
According to the National Multiple Sclerosis Society (NMSS), the direct costs of medical care for MS patients in the United States exceed $6 billion annually. Additionally, a recent NMSS analysis estimated the total cost of MS, including medical and non-medical care, production losses, and informal care, at more than $47,000 per U.S. patient per year.
Fampridine-SR is a sustained-release tablet formulation of the investigational drug fampridine (4-aminopyridine, or 4-AP). Data collected in laboratory studies found that fampridine can improve the communication between damaged nerves, which may result in increased neurological function.
Fampridine-SR Mechanism of Action
A nerve cell has one extension, called an axon, which it uses to communicate via electrical signals to other nerve cells. All but the smallest axons have a special covering of a fatty substance called myelin that acts as insulation to preserve and speed these nerve signals, much like the insulating cover of an electrical cord helps preserve the transmission of electricity.
In MS, the myelin becomes damaged and the axon cannot effectively transmit electrical impulses. Specifically, the damaged myelin exposes channels in the membrane of the axon, which allow potassium ions to leak from the axon, dissipating the electrical current. Fampridine-SR blocks these exposed channels, and helps the electrical signals to pass through areas of damage.
Acorda will hold a webcast this evening at 7 p.m. Eastern Time. Study data will be presented and members of the Acorda management team will be available for a question and answer session. To access the webcast please log on to http://phx.corporate-ir.net/phoenix.zhtml?p=irol-eventDetails&c=194451&eventID=1529938
(Due to its length, this URL may need to be copied/pasted into your Internet browser's address field. Remove the extra space if one exists.)
Forward Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, regarding management's expectations, beliefs, goals, plans or prospects should be considered forward-looking. These statements are subject to risks and uncertainties that could cause actual results to differ materially, including Acorda Therapeutics' ability to successfully market and sell Zanaflex Capsules, the risk of unfavorable results from future studies of Fampridine-SR, delays in obtaining or failure to obtain FDA approval of Fampridine-SR, competition, the ability to obtain additional financing to support Acorda Therapeutics' operations, unfavorable results from its preclinical programs, and failure to protect its intellectual property or to defend against the intellectual property claims of others. These and other risks are described in greater detail in Acorda Therapeutics' filings with the Securities and Exchange Commission. Acorda Therapeutics may not actually achieve the goals or plans described in its forward-looking statements, and investors should not place undue reliance on these statements. Acorda Therapeutics disclaims any intent or obligation to update any forward-looking statements as a result of developments occurring after the date of this press release.
About Acorda Therapeutics
Acorda Therapeutics is a biotechnology company developing therapies for SCI, MS and related nervous system disorders. The Company's marketed products include Zanaflex Capsules(TM) (tizanidine hydrochloride), a short-acting drug for the management of spasticity. For full prescribing information, please go to www.zanaflexcapsules.com. Acorda's lead clinical stage product, Fampridine-SR, recently completed a Phase 3 study in people with MS. The Company's pipeline includes a number of products in development for the treatment, regeneration and repair of the spinal cord and brain.
CONTACT: Acorda Therapeutics, Inc.
Director, Corporate Communications
Rooney and Associates Communications
SOURCE: Acorda Therapeutics, Inc.
The immune system's ability to police itself may offer a new method of arresting the cells responsible for autoimmune diseases such as multiple sclerosis and for the rejection of transplanted organs and tissues, scientists at Dana-Farber Cancer Institute report in a study in the May issue of the journal Immunity, available online.
Because the technique utilizes the body's own mechanism for controlling the immune system, it may prove more effective and less prone to side effects than current therapies, which take a less direct approach, the study authors indicate. Although the research was done in mouse cells, it is likely to apply to humans because of strong similarities between mouse and human immune cells.
"We found that when we block a key interaction between two types of immune system cells, one of those types -- which is often associated with autoimmune disease and tissue rejection -- is attacked and dies," says senior author Harvey Cantor, MD, of Dana-Farber. "The fact that this approach uses the body's natural system for regulating the immune response encourages us that it can be the basis of an effective therapy for a variety of immunological conditions."
Autoimmune disease and tissue rejection pose a complex challenge to scientists. Both problems result from an attack by immune system cells -- which are trained to detect and destroy infected or diseased tissue -- on parts of the body where it isn't wanted. In the case of rejection, they recognize transplanted tissue as foreign and mount an assault on it. In autoimmune diseases, they attack the body's own tissue as through it were foreign.
Conventional therapies for these conditions can have serious drawbacks. Many of them rely on natural substances called antibodies, which wedge inside "receptors" on immune system T cells. The coupling blindfolds T cells to the presence of foreign or diseased tissue, blunting their ability to spark an immune attack.
Antibody-based treatments fall short for a variety of reasons: the antibodies often fail to fit securely inside T cells receptors, so the immune response is only slightly reduced; or the antibodies succeed in blocking the receptor, but that inadvertently causes the T cells to launch a more ferocious attack. In other cases, antibodies work too well, suppressing the entire immune system, rather than just a portion of it, leaving patients susceptible to dangerous infections.
To overcome these problems, researchers have tried to harness the body's natural system for quieting the immune response. One intriguing approach involves the immune system's "natural killer," or NK, cells. Scientists have long known that some NK cells can kill a class of T cells -- known as CD4 T cells -- that have been activated to fight infection, but that NK cells are often restrained from doing so.
Cantor and his colleagues theorized that when a tiny hook, or ligand, called Qa-1-Qdm on activated CD4 T cells latches onto the NKG2A receptor on NK cells, the T cells are protected from destruction. To test this, they produced activated T cells that either lacked the Qa-1-Qdm receptor or had a faulty version of it, preventing them from binding to the NKG2A receptor. The result was that the T cells became vulnerable to attack from a set of NK cells. Using an antibody to block the connection between Qa-1-Qdm and NKG2A had the same result.
"Our findings suggest that it is possible to use antibodies to trigger the body's own mechanism for suppressing the immune response," Cantor remarks. "The results serve as a proof of principle that this approach can be applied to the treatment of conditions characterized by an excessive or unwanted immune response."
While the work was done with mouse cells, the Qa-1-Qdm ligand has the same shape and structure in human and mouse T cells, raising hopes that the approach will prove effective in humans as well, adds Cantor, who is also a professor of pathology at Harvard Medical School.
The research was supported by grants from the National Institutes of Health, the National Multiple Sclerosis Society, the Claudia Adams Barr Foundation, and a fellowship from Taiho Pharmaceuticals of Japan.
The lead author of the study is Linrong Lu, PhD, of Dana-Farber. Co-authors include Koichi Ikizawa, PhD, Dan Hu, PhD, Miriam Werneck, and Kai Wucherpfennig, MD, PhD, all of Dana-Farber.
Dana-Farber Cancer Institute (http://www.danafarber.org/) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
Contact: Bill Schaller
Dana-Farber Cancer Institute
Washington, May 25 : Scientists in New York City are using a unique electrical stimulation device that restores mobility in patients with foot drop, a partial leg paralysis that often afflicts stroke survivors.
Presently, the 'NESS L300' neuro-rehabilitation system is available only at the Cornell University Weill Medical Center, one of the two medical centres that compose NewYork-Presbyterian Hospital.
The device is worn on the lower-leg and foot in place of a traditional foot brace. It contains sensors that detect whether the patient's foot is in the air or on the ground, and electrodes that transmit painless electrical stimulation to the peroneal nerve to activate the calf muscle and correct their gait.
Doctors at the medical centre have also shown that the device improves walking co-ordination, speed and blood flow, and decreases the effort required in walking.
"Our patients have been very enthusiastic about this remarkable device, which, together with a comprehensive rehabilitation regimen, has helped them retrain and regain control of their bodies and achieve greater mobility and independence," says Dr. Michael O'Dell, acting chief of rehabilitation medicine and medical director of the Inpatient Rehabilitation Medicine Center at NewYork-Presbyterian/Weill Cornell.
Manufactured by California based Bioness Inc., the device may also be beneficial in treating patients with traumatic brain injury, multiple sclerosis, and cerebral palsy.
Boffins, however, agree that further research is required to determine the specific long-term benefits of the NESS L300.
Thursday, May 24, 2007
Studies Show Multiple Sclerosis Patients Taking Rituxan Have Fewer Brain Lesions
By Charlene Laino
WebMD Medical News
Reviewed by Louise Chang, MD
May 1, 2007 (Boston) -- A drug that is already used to treat cancer and rheumatoid arthritis cut by more than half the chance that people with multiple sclerosis would have their symptoms flare up over a six-month period, researchers report.
In two early studies, people taking the drug, Rituxan, also had fewer areas of damage, or lesions, in their brain than those on placebo.
"We believe that if we can prevent these lesions, we can modify the course of this disease," says researcher Stephen Hauser, MD, chairman of neurology at the University of California, San Francisco, and president of the American Neurological Association.
If the research pans out, "this would be a very attractive and probably blockbuster therapy," he tells WebMD.
The research was presented at the American Academy of Neurology's 59th Annual Meeting.
How Rituxan Works
The exact cause of multiple sclerosis (MS) is unknown. But the disease is thought to be triggered by a malfunction in the immune system that prompts immune cells to attack the brain and/or spinal cord. The most common form of multiple sclerosis is a relapsing-remitting form in which relapses or "attacks" of worsening neurologic function appear, and then disappear, for months or years at a time.
Like many other drugs for MS, Rituxan targets the immune system to help calm the inflammation that scars nerves, leading to disease progression. But Rituxan homes in on the immune system in a brand new way, Hauser says.
The drug works by targeting cells in the immune system called B cells, which make antibodies that contribute to the disease process. B cells also secrete chemicals that can encourage inflammation, he says.
Though never compared head-to-head, the early research hints that the drug is twice as effective as drugs such as interferon that are now used to treat multiple sclerosis, he says.
Also, it's more convenient, requiring only two infusions every six months or so instead of the daily to weekly injections associated with current therapies, Hauser says.
Fewer Flare-ups in People on Rituxan
Both of the new studies involved people with the relapsing-remitting form of MS. In the first study, 69 people were given two one-hour infusions of Rituxan two weeks apart and 35 were given a placebo.
Over the next six months, 58% fewer people taking the drug had their symptoms flare up than those taking placebo: 14.5% of those on Rituxan experienced at least one relapse compared with 34.3% of those receiving a placebo.
Also, those on Rituxan had 91% fewer brain lesions seen on MRIs than those on placebo, Hauser says.
The second study, designed to look at the safety of the drug, showed "no unexpected problems," says researcher Amit Bar-Or, MD, of the Montreal Neurological Institute at McGill University in Montreal.
Twenty-six of 28 people were able to complete the 48-week study, in which they received two infusions of Rituxan two weeks apart and then another course six months later.
Most side effects were limited to mild to moderate reactions to the drug infusion, such as headaches and chills, Bar-Or tells WebMD. The two people who dropped out had infusion-related headaches.
Both studies were supported by Genentech Inc., and Biogen Idec., the companies that market the drug for certain types of lymphoma and for a moderate to severe form of rheumatoid arthritis in the U.S.
Safety a Concern
Gary Birnbaum, MD, director of the Multiple Sclerosis Treatment and Research Center in Golden Valley, Minn., says a big worry is a rare but rapidly fatal viral infection known as progressive multifocal leukoencephalopathy, or PML.
And while people on Rituxan appear to have fewer MS flare-ups, "we still don't know if it will actually stop disease progression," Birnbaum tells WebMD.
"These are important observations," Birnbaum says. "But we need longer trials to assess safety and effectiveness."
Immediate Drug Therapy Better Than Waiting
In a third study presented at the meeting, researchers reported that people who immediately start taking Betaseronat the first signs of MS are 41% less likely to have another attack over the next three years than those who delay treatment until they are diagnosed, as is currently done.
Betaseron is a brand of the interferon beta medications that are already used to treat people with relapsing-remitting MS. Other brands of interferon beta, which may reduce the frequency of relapses and delay disability, are Avonex and Rebif.
"I was one of those skeptics who told patients [who had one attack] we could wait," says researcher Mark S. Freedman, MD, director of the Multiple Sclerosis Unit at the University of Ottawa.
"But it turns out there is an 80% chance a person who has one attack will meet the criteria for MS by two years," he tells WebMD. "Immediate treatment can prevent or delay the chance of progression."
Freedman says it's possible that immediate treatment with the other interferon beta medications would provide the same benefit. "But it hasn't been shown."
SOURCES: American Academy of Neurology 59th Annual Meeting, Boston, April 29-May 5, 2007. Stephen Hauser, MD, chairman of neurology, University of California, San Francisco; president, American Neurological Association. Gary Birnbaum, MD, director, Multiple Sclerosis Treatment and Research Center, Golden Valley, Minn. Amit Bar-Or, MD, Montreal Neurological Institute, McGill University, Montreal. Mark S. Freedman, MD, director, Multiple Sclerosis Unit, University of Ottawa.
© 2007 WebMD, Inc. All rights reserved.
Opexa Therapeutics Completes Patient Enrollment in Phase IIb Trial of Tovaxin™ for Treatment of Multiple Sclerosis
THE WOODLANDS, Texas--(BUSINESS WIRE)--Opexa Therapeutics, Inc. (NASDAQ:OPXA), a company involved in the development and commercialization of cell therapies, today announced the completion of patient enrollment in a 150-patient Phase IIb safety and efficacy study (TERMS). The trial design is a U.S. multicenter, randomized, double-blind, placebo-controlled study of subcutaneous Tovaxin™ in subjects with Clinically Isolated Syndrome (CIS) or Relapsing/Remitting Multiple Sclerosis (RRMS).
Patients participating in the study, which is being conducted under Opexa’s U.S. Investigational New Drug (IND) application filed with the U.S. Food and Drug Administration (FDA), will receive 52 weeks of treatment and will undergo safety and efficacy assessments using primary criterion of gadolinium-enhancing lesions and secondary criterion of annualized relapse rate. The Company will collect descriptive analysis data on the first 75 subjects to reach 6 months evaluable later this year. This trial was specifically designed, with the assistance of well-known multiple sclerosis experts, to address three important objectives: to rigorously assess the safety and efficacy of Tovaxin, to maintain a robust clinical effect for the full study, and to provide a scientific and clinical database for advancement to Phase III.
David McWilliams, president and chief executive officer of Opexa Therapeutics, stated, "Full enrollment in this Phase IIb study is an important milestone in the commercialization of Tovaxin. With this milestone achieved, we now look forward to reporting a descriptive analysis in the fourth quarter of 2007 and the full data results in the second half of 2008." McWilliams continued, "I am convinced that the ability to rapidly enroll this study across 35 U.S. centers reflects the high level of interest by multiple sclerosis patients in new safe and effective treatments."
Edward Fox, MD, PhD and lead principal investigator for the Phase IIb study, commented, "If the results of this study can replicate the safety and effectiveness demonstrated in earlier studies, I believe Tovaxin could be an important advance in treating patients with MS. I’m pleased that the positive response from physicians and their MS patients across the country has resulted in the rapid enrollment of this study."
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™. The observed regulatory immune responses have been shown to collectively correlate with clinical improvement in treated patients.
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.
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.
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 Phase IIb trials. The Company holds the exclusive worldwide license for adult multipotent stem cells derived from mononuclear cells of peripheral blood. The technology allows large quantities of monocyte derived stem cells to be produced efficiently for use in autologous therapy, thus circumventing the threat of rejection. The Company is in preclinical development for diabetes mellitus. For more information, visit the Opexa Therapeutics website at www.opexatherapeutics.com.
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.
March 14, 2007 — Portland, Ore. — Artielle ImmunoTherapeutics, Inc. today announced that the Company has initiated a Phase I clinical trial to evaluate its novel drug candidate, RTL1000, for the treatment of multiple sclerosis (MS). RTL1000 is a novel protein drug with a highly-selective mechanism of action that targets pathogenic T-cells responsible for triggering and sustaining MS.
The trial is currently open for enrollment and is a multi-center, double-blind, placebo controlled, single dose Phase I study to be conducted with 30 MS patients in the United States. The clinical trial is designed to assess the safety and pharmacokinetic properties of RTL1000. The study will be conducted at research centers located in New Haven, Connecticut; Indianapolis, Indiana; Kansas City, Kansas; Baltimore, Maryland; Portland, Oregon and Seattle, Washington. Clinical trial information can be obtained at:
“The initiation of Phase I clinical trials is an important milestone for Artielle” said Al Ferro , Ph.D., President and CEO of Artielle. “In addition to demonstrating that RTL1000 is safe for human use, this initial trial is designed to provide pharmacokinetic and mechanistic data that will enable us to plan for later-stage clinical trials.”
“RTL1000 has demonstrated impressive pre-clinical data in several different disease models and has the potential to add significantly to the clinical options for patients with this disease,” said Dennis Bourdette, M.D., Chair & Swank Professor, Department of Neurology, Oregon Health & Science University (OHSU). “There remains a critical unmet need for new therapies for this disease and I am delighted to be involved with this program.”
“The highly selective mechanism of action of this drug suggests it could have a very interesting profile as a new therapy. It targets only those cells involved in the disease process” said Arthur Vandenbark, Ph.D. Senior Research Career Scientist at the Portland Veteran Affairs Medical Center and Professor in the Department of Neurology and Department of Molecular Microbiology & Immunology at OHSU. “We look forward to seeing this therapy advance into human testing”
About Multiple Sclerosis
MS is a chronic autoimmune disease of the central nervous system. The damage to the central nervous system is caused by the destruction of the myelin sheath surrounding the nerve axons. The result is that the exposed axons are no longer able to send messages required to control movement, speech, and a wide variety of bodily functions. This debilitating disease affects about 400,000 Americans and about 2.5 million people worldwide.
MS is caused when T cells, part of the body’s immune system, target nerves in the spinal cord and brain creating lesions in the myelin sheath. In MS, activation of these T cells triggers the release of inflammatory cytokines that lead to the destruction of the myelin. RTL1000 disrupts the activation of the T cells, preventing the release of the inflammatory cytokines and causing the release of anti-inflammatory cytokines. RTL1000 has been found to be both safe and efficacious in animal models of MS.
About Artielle ImmunoTherapeutics
Artielle ImmunoTherapeutics is a privately held biotechnology company based in Tigard, Oregon. Artielle’s research is focused on the development of therapeutics for the treatment of autoimmune diseases. In addition to its multiple sclerosis drug, the Company is developing drugs for the treatment of Rheumatoid Arthritis, Celiac Disease and Uveitis. Artielle has acquired the exclusive worldwide rights to these technologies from OHSU. For more information on the Company, visit www.artielle.com.
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Risk to confirmed EDSS progression reduced by 40 percent compared to delayed treatment
BOSTON – Bayer HealthCare Pharmaceuticals announced today new data, which show that immediate initiation 1 of Betaseron ® (interferon beta1b) treatment in patients with a first event suggestive of multiple sclerosis (MS) can significantly reduce the risk of permanent neurological impairment as measured by the Expanded Disability Status Scale (EDSS) by 40 percent 2 over three years compared to delayed treatment 3 . These findings from the BENEFIT (Betaseron in Newly Emerging multiple sclerosis For Initial Treatment) studies 4 were presented today at the American Academy of Neurology’s 59th Annual Meeting in Boston, Massachusetts.
“Some patients have already developed significant neurological damage when they first present with signs of MS, which can lead to accumulated disability later in life. The BENEFIT results clearly show that immediate treatment with Betaseron initiated after the first clinical event can significantly reduce that damage, which could translate into a greater delay in the time it takes for patients to suffer from the debilitating consequences of MS,” said Dr. Mark S. Freedman, Professor of Neurology at the University of Ottawa and investigator of the study. “This is a truly novel finding that has not yet been demonstrated for any other immunomodulatory MS treatment, and underscores the urgent need to treat patients early rather than waiting for further signs of MS to develop. Physicians and patients should consider these unprecedented findings when making treatment decisions.”
“We are delighted that the BENEFIT study continues to deliver groundbreaking results,” said Darlene Jody, M.D., Senior Vice President and President, of Bayer Healthcare’s Specialty Therapeutics Global Business Unit. “In the past year, Betaseron has received approval around the world for use in patients after the first event suggestive of MS. We intend to submit this novel data for inclusion in our label. Regulatory approval would further differentiate Betaseron from other products in the market place and strengthen our position.”
BENEFIT is a multicenter trial conducted at 98 sites in 20 countries and included patients presenting with a single clinical episode suggestive of MS. A total of 468 patients with a first clinical demyelinating event suggestive of MS and typical MRI findings were randomized to receive either 250 micrograms of interferon beta1b (Betaseron) every other day or placebo as a
subcutaneous injection in a double blind fashion. The placebocontrolled treatment period lasted up to 24 months or up to the time when patients were diagnosed with clinically definite MS. All study participants were then invited to participate in a followup study with Betaseron to prospectively assess the impact of such immediate versus delayed treatment with Betaseron on the longterm course of the disease for a total observation time of five years.
Results from a prospectively planned analysis of patients three years after the first event suggestive of MS showed that:
- Immediate treatment with Betaseron after the first event suggestive of MS reduced the risk for confirmed EDSS progression by 40 percent over three years compared to delayed treatment.
- At three years, patients who initiated Betaseron treatment immediately were 41 percent 5 less likely to progress to clinically definite MS versus patients who began treatment later. These results confirm the findings of the placebo-controlled BENEFIT study.
At the end of three years, 73 percent of patients were on Betaseron treatment after the first event suggestive of MS.
Betaseron (Interferon beta1b) is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis.
The most commonly reported adverse reactions are lymphopenia, injectionsite reaction, asthenia, flulike symptom complex, headache and pain. Gradual dose titration and use of analgesics during treatment initiation may help reduce flulike symptoms. BETASERON should be used with caution in patients with depression. Injectionsite necrosis has been reported in 4% of patients in controlled trials. Patients should be advised of the importance of rotating injection sites. Female
patients should be warned about the potential risk to pregnancy. Cases of anaphylaxis have been reported rarely. See “Warnings,” “Precautions,” and “Adverse Reactions” sections of full Prescribing Information.
About Bayer HealthCare Pharmaceuticals
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.
# # #
Media Contact: Marcy Funk, Bayer HealthCare (973) 305 5385
This news release contains forwardlooking 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 20F).
The company assumes no liability whatsoever to update these forwardlooking statements or to conform them to future events or developments.
1 “Immediate initiation” or “immediate treatment” is treatment initiated after the first clinical event.
2 By proportional hazards regression, adjusted for T2lesion volume at screening.
3 “Delayed treatment” is treatment initiated after the second clinical event or after 2 years, whichever is first.
4 Mark S. Freedman, et al: Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT): Effects of
Immediate vs. Early Onset of Interferon Beta1b Treatment, American Academy of Neurology, 59th Annual Meeting.
5 By proportional hazards regression, adjusted for a standard set of covariates.
Preclinical Studies Suggest FTY720 Mechanisms In Multiple Sclerosis May Include Direct Activity In The Brain
New preclinical data, presented at the American Academy of Neurology (AAN) annual meeting in Boston, reflect the expanding understanding of FTY720's (fingolimod) mechanism of action in multiple sclerosis (MS), suggesting direct beneficial effects in the brain. The data suggest that FTY720 may have the potential to reduce neurodegeneration and enhance repair of the central nervous system (CNS) by modulating S1P receptors expressed on brain cells. Separately, new clinical data presented from the six-month Phase II study found that the proportion of patients with clinical depression was significantly lower in the FTY720 groups compared to placebo.
These new preclinical data add to a growing body of evidence that FTY720 has multiple, specific mechanisms of action. The ongoing Phase III clinical development program includes comprehensive monitoring to further understand the clinical and safety implications of these mechanisms of action.
MS is a progressive and debilitating disorder of the CNS that frequently affects young people, women twice as often as men. It is caused by the destruction of myelin, which helps neurons carry electrical signals in the brain. MS is the most common inflammatory and neurodegenerative disorder of the CNS, causing problems with muscle control and strength, vision, balance, sensation and mental function. MS typically presents in relapsing forms involving acute self-limiting attacks of neurological dysfunction (or "relapses") followed by complete or partial restoration of functions.
FTY720's previously known activity is based on its ability to bind to the sphingosine 1-phosphate receptor-1 (S1P-R1) on circulating lymphocytes (white blood cells). This activity reversibly traps a proportion of lymphocytes in the lymph nodes, reducing the number of inflammatory T-cells circulating in the bloodstream and in the CNS.
One of the preclinical studies presented at AAN evaluated FTY720's ability to activate S1P receptors on astrocytes in cell culture. Astrocytes are known to play an active role in nervous tissue repair, and to regulate the permeability of the blood brain barrier. The study findings indicate that FTY720 activates S1P receptors on astrocytes, stimulating intracellular pathways that regulate a variety of functions, such as cell proliferation and migration. (Muellershausen et al)
A second study, also conducted in cell culture, demonstrated that FTY720 improved the survival and increased the number of immature and mature oligodendrocytes - cells that help form myelin in the CNS. Stimulation of S1P receptors on oligodendrocytes may help limit demyelination and/or promote myelin repair. (Barske et al)
In the third study, conducted in an established animal model of MS [experimental autoimmune encephalomyelitis (EAE) in rats], researchers found that FTY720 directly administered in the rat brain significantly suppressed the severity of clinical EAE, suggesting additional mechanisms of action independent of lymphocyte depletion. In imaging studies, enhanced myelination and axonal protection associated with the clinical effects were confirmed in animals receiving oral FTY720. (Schubart et al)
Clinical results in depression (Kappos et al)
Data from the six-month placebo-controlled Phase II study of once-daily oral FTY720 in patients with MS found that the proportion of patients with clinical depression was significantly lower in the FTY720 groups at six months compared to placebo. Depression is a common co-morbid condition in people with MS; the presence of depression in MS may reduce adherence to disease-modifying therapy and lead to higher rates of treatment discontinuation.
The Phase II study included 281 patients, randomized to receive FTY720 1.25 mg, FTY720 5 mg, or placebo. Depression was evaluated in 239 patients using the Beck Depression Inventory - Second Edition (BDI-II). BDI-II scores of 14 or more suggest clinical depression. At baseline, mean BDI-II scores were 9.3 for patients randomized to receive FTY720 1.25 mg, 8.0 for patients randomized to receive FTY720 5 mg, and 9.1 for patients randomized to receive placebo. At month six, patients receiving FTY720 1.25 mg had the most improvement in depression symptoms (BDI-II = 7.9, mean change from baseline = -1.45). Patients receiving FTY720 5 mg had no change in mean BDI-II scores, and patients receiving placebo showed worsening (BDI-II=10, mean change from baseline = +0.94). The proportions of patients with BDI-II scores indicating clinical depression were significantly lower in both FTY720 groups when compared with the placebo group at month six: 33% of patients receiving placebo versus 17% of patients receiving FTY720 1.25 mg (p=0.0176) and 19% of patients receiving FTY720 5 mg (p=0.0407).
FTY720 is a novel oral drug that is currently in a worldwide Phase III clinical development program as a once-daily, disease modifying therapy for relapsing MS. Previously reported Phase II results showed that patients treated with FTY720 had a significant reduction in relapses and in inflammation as measured on Magnetic Resonance Imaging (MRI) compared to placebo at six months and that low disease activity was maintained over two years. Up to 77% of patients remained relapse free and more than 80% of patients were free from lesions showing active inflammation on MRI after two years of continuous FTY720 treatment. Patients who received placebo for the first six months of the study also experienced a marked improvement after switching to FTY720 in the extension, and low disease activity was sustained through month 24.
The Phase III clinical trials program includes FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis), a 24-month, randomized, double-blind, placebo-controlled study program that plans to include over 2,000 patients worldwide with the relapsing-remitting form of MS, and TRANSFORMS (TRial Assessing injectable interferoN vS FTY720 Oral in RrMS), an international 12-month, randomized, double-blind study comparing FTY720 to Interferon-beta-1a (Avonex®, i.m. once weekly). For more information about the clinical trial program, including eligibility criteria and location of U.S. study sites, patients can call the following toll-free number: 866-788-3930, or visit www.MSClinicalTrials.com.
In the six-month placebo-controlled phase of the Phase II study, the most frequent adverse events reported for FTY720 were dose-dependent upper respiratory tract infections (mainly nasopharyngitis) and dyspnea, plus diarrhea and nausea. FTY720 treatment was associated with initial dose-dependent decreases in heart rate and expiratory air flow. Clinically asymptomatic increases in alanine aminotransferase (liver enzyme) and an increase in blood pressure were also observed. No unexpected adverse events emerged in patients treated for up to 24 months compared with the six-month placebo-controlled phase. There was no further elevation of blood pressure with continued treatment beyond the effect seen at six months. The ongoing Phase III study program includes comprehensive monitoring, which will provide further characterization of the safety profile of FTY720.
This release contains certain forward-looking statements relating to Novartis' business, which can be identified by the use of forward-looking terminology such as "may," "suggest," "suggesting," "potential," "growing body of evidence," "plans to include" or similar expressions, or by express or implied statements regarding the potential approval of FTY720 by health authorities for marketing, whether or not FTY720 will be the first orally effective MS treatment, the potential health effects or long-term impact of a patient's use of FTY720, or potential future revenue from FTY720. Such forward-looking statements reflect the current views of Novartis regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with FTY720 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that FTY720 will be approved for any indications or labeling in any market. Neither can there be any guarantee that, if approved, it will be the first orally effective MS treatment approved. Neither can there be any guarantee regarding the health effects or long-term impact of a patient's use of FTY720. Neither can there be any guarantees that FTY720 will reach any particular levels of revenue. In particular, management's expectations regarding FTY720 could be affected by, among other things, unexpected clinical trial results, including new clinical trial results and additional analysis of existing results; unexpected regulatory actions or delays or government regulation generally; competition in general; Novartis' ability to obtain or maintain patent or other proprietary intellectual property protection; government, industry and general public pricing pressures, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
Novartis Pharmaceuticals Corporation develops, manufactures, markets and sells leading innovative prescription drugs used to treat a number of diseases and conditions, including those in the cardiovascular, metabolic, cancer, organ transplantation, central nervous system, dermatological, gastrointestinal and respiratory areas. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
Novartis has been a leader in the neuroscience area for more than 50 years, having pioneered early breakthrough treatments for Alzheimer's disease, Parkinson's disease, Attention Deficit Hyperactivity Disorder, epilepsy, schizophrenia and migraine, many of which continue to be regarded as "gold standards" to this day. Novartis Neuroscience continues to be at the forefront of research and development of new compounds, is committed to addressing unmet medical needs and to supporting patients and families affected by these disorders.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS), a world leader in offering medicines to protect health, treat disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. Novartis is the only company with leadership positions in both patented and generic pharmaceuticals. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 101,000 associates and operate in over 140 countries around the world.
Science Daily — Oregon Health & Science University neuroscientists are eyeing a protein as a potential therapeutic target for multiple sclerosis because de-activating it protects nerve fibers from damage.
OHSU researchers, working with colleagues at the Portland Veterans Affairs Medical Center and the University of Padova in Italy, have shown that genetically inactivating a protein called cyclophilin D can protect nerve fibers in a mouse model of multiple sclerosis. Cyclophin D is a key regulator of molecular processes in the nerve cell's powerhouse, the mitochondrion, and can participate in nerve fiber death. Inactivating cyclophilin D strengthens the mitochondrion, helping to protect nerve fibers from injury. The findings are published in Proceedings of the National Academy of Sciences.
"We're extremely excited," said Michael Forte, Ph.D., senior scientist at the Vollum Institute at OHSU and the study's lead author. "While we can't genetically inactivate cyclophilin D in people, there are drugs out there that can block the protein. Our research predicts that drugs that block cyclophilin D should protect nerve fibers from damage in MS."
Such a drug would be the first therapy specifically for secondary-progressive MS, one of the more debilitating forms of MS involving an initial period of relapsing and remitting, followed by a steady worsening of symptoms. It affects half of the estimated 2 million people with MS.
The only available therapies for MS are anti-inflammatory drugs, which reduce the inflammation believed to spur certain T-cells in the body to attack myelin, the fatty sheath insulating nerve fibers in the brain and spinal cord. The fibers can't conduct impulses, leading to paralysis, memory loss, dizziness, fatigue, pain and imbalance. Over time, the nerve fibers themselves degenerate, leading to permanent functional deficits.
"All MS drugs available right now are anti-inflammatory," said study co-author Dennis Bourdette, M.D., professor and chairman of neurology in the OHSU School of Medicine, and director of the OHSU MS Center of Oregon. "What is desperately needed is a therapeutic that protects the nerve fibers from degeneration."
In recent years, scientists have increasingly viewed MS as a neurodegenerative disorder rather than simply an inflammatory one. Loss of nerve cells, injury to nerve fibers and atrophy within the central nervous system occur progressively from the start of the disease, eventually leading to permanent disability, especially in patients who've had MS for many years.
"What puts people in wheelchairs from MS is not an inflammatory attack on myelin of the central nervous system. It's the severing of the axons (nerve fibers), which is a permanent thing," Forte said.
Inflammation triggers a chain of molecular events that leads to progressive nerve fiber deterioration in MS, including the development of free radicals such as reactive oxygen and nitrogen that slow the cell's energy generation capability. It also throws off mitochondrial function by causing calcium to build up in the cell, reducing levels of ATP that serves as the cell's fuel source.
But scientists believe that cyclophilin D is responsible for causing the unregulated opening of a pore in the mitochondrion's membrane that allows the calcium overload. The OHSU team showed that mice lacking cyclophilin D still developed an MS-like disease, but unlike their counterparts possessing the protein, the mutant mice partially recovered. Scientists found their nerve fibers remained intact, and they resisted the free radicals and calcium overload.
"What we've done is make it so the mitochondria can tolerate higher loads of calcium before they die," Forte said. "The mutant mice are protected from axonal damage associated with this MS-like disease in mice."
The scientists are now testing drugs that could be used to shut down the cyclophilin D protein and the mitochondrion pore it activates. "If you basically inhibited that protein with a drug, you would see the same axonal preservation that you saw in the mutant mouse," Forte said.
One class of compounds Forte and Bourdette are particularly interested in is non-immunosuppressive derivative of cyclosporin A (CsA). Some nonimmunsuppressive derivatives of cyclosporin A are in human trials for other conditions.
Because these drugs are already being tested in humans, they could be rapidly tested in MS. Bourdette believes that a cyclophilin D antagonist could potentially become available as a treatment for MS within five years.
"We don't have to invent the drugs to target this protein. They already exist," Bourdette said.
Such a therapy can't come soon enough for 36-year-old West Linn, Ore. resident Laura Wieden, who has suffered since 1995 from relapsing-remitting MS that's caused weakness in both legs and forced her to ride a Segway personal transportation device or a wheelchair. "For me, it's fabulous," she said. "If you can prevent MS, that's great, but what about the millions of people who have it? They need something that keeps the cells from dying. This just holds so much promise."
Wieden's father, Dan Wieden, co-founder of Portland-based Wieden + Kennedy advertising agency, set up a fund in his daughter's name -- the Laura Fund for Innovation in Multiple Sclerosis Research -- to support MS research that pushes traditional boundaries to discovery. The discovery by Forte, Bourdette and their team, which was funded in part by the foundation, fits the bill, he said.
"It goes to prove that sometimes the big breakthroughs do not come from the more traditional lines of inquiry," he said.
"What I appreciate about our relationship with OHSU is that there seems to be a sense of urgency about these projects. And it's been beneficial for us to develop a more personal relationship with the researchers. That way it becomes not just an academic exercise, but a very passionate inquiry on their part."
Other study funders were the National Institutes of Health, the Department of Veterans Affairs and the Nancy Davis Center Without Walls.
Note: This story has been adapted from a news release issued by Oregon Health & Science University.
By Randy Dotinga
Monday, May 14, 2007; 12:00 AM
MONDAY, May 14 (HealthDay News) -- Testosterone gel may slow the progression of multiple sclerosis in men with the disease, a new study suggests.
Only 10 men took part in the research, all had milder forms of MS, and more studies will be needed before doctors determine whether the treatment really works. Still, the researchers were impressed that the men's mental decline ceased, and the shrinking of their brains returned to the normal levels expected due to aging.
"We saw an improvement which was exciting," said study co-author Dr. Rhonda Voskuhl, professor of neurology at the University of California, Los Angeles. "This looks like it would be neuroprotective, which would be great."
But another expert, Dr. Moses Rodriguez, professor of neurology and immunology at the Mayo Clinic, said he was skeptical that the treatment would become common and noted that MS research has had a history of promising therapies that ultimately failed.
A treatment that protects the central nervous system against multiple sclerosis would be a major breakthrough for the 400,000 Americans with the disease. MS is thought to be caused when the immune system attacks the myelin sheath, a fatty substance that insulates nerves in the brain and spinal cord. It can cause a wide range of symptoms, from cognitive decline and pain to severe fatigue and difficulty walking. Most people with the disease have normal or near-normal life spans.
Women are two to three times more likely to get the disease, and there has been speculation that testosterone -- the male hormone -- could protect men against MS.
While injection drugs can slow the progress of the disease, researchers have been trying to find a way to boost their effectiveness.
In the new study, the researchers followed 10 men with mild MS who, for a variety of reasons, chose not to take injection treatments. The average age of the participants was 46. After the researchers monitored the men's conditions for six months, each man applied 10 grams of a gel containing 100 milligrams of testosterone to his upper arms once daily for 12 months.
"The cognition improved instead of declining," Voskuhl said. "We were pretty surprised by seeing an improvement." The study authors also found that the rate of brain atrophy declined by two-thirds, to the rate expected during normal aging. In another promising sign, the men ended up with more muscle mass after undergoing the treatment.
Unfortunately, testosterone treatment would not be feasible in women because of its side effects, Voskuhl said. But researchers are looking into other possible treatments for women.
Voskuhl also thinks that testosterone treatment -- if it turns out to work in other studies -- could lead to better therapies for diseases such as Alzheimer's and Parkinson's.
The findings are published in the May issue of theArchives of Neurology.
But the Mayo Clinic's Rodriguez, who's familiar with the study findings, said he doubts that testosterone therapy will become standard, because it has side effects and has been connected to an increased risk of prostate cancer. Also, much promising but preliminary MS research fails to bear fruit, he said.
Voskuhl said further research will take three to five years, largely because it takes time to get funding. Doctors could legally give testosterone to MS patients now, but she said it's not approved for that purpose.
"You really should wait until the larger trials are finished and we go for FDA (U.S. Food and Drug Administration) approval," Voskuhl said.
However, Rodriguez believes MS patients would be taking a "great risk" if they underwent testosterone treatment before it was federally approved for that purpose.
Learn more about MS from the National Multiple Sclerosis Society.
SOURCES: Rhonda Voskuhl, M.D., professor of neurology, University of California, Los Angeles; Moses Rodriguez, M.D., professor of neurology and immunology, Mayo Clinic, Rochester, Minn.; May 2007,Archives of Neurology
Thu May 24, 2007 12:34 PM BST
LONDON, May 24 (Reuters) - GlaxoSmithKline Plc (GSK.L: Quote, Profile , Research) said on Friday it had appointed Dr. Jingwu Zang to head a major new research and development centre in Shanghai, which would focus on neurodegenerative diseases.
The centre aims to create new drugs for disorders like multiple sclerosis, Parkinson's and Alzheimer's disease. It will eventually direct global discovery and development activities in its therapeutic area, from drug-target identification to late-stage clinical studies.
Zang, the founding director and a professor at the Institute of Health Sciences in Shanghai, will take up his position in June.
Glaxo's research head Moncef Slaoui, who told its annual meeting on Wednesday that an announcement on building a fully integrated R&D centre in China was imminent, said the move marked a significant expansion of the group's research effort.
"We intend to be part of a future in which the phrase 'discovered in China' is heard as often as 'made in China' is heard today," he said in a statement.
Glaxo already has an R&D presence in China via collaborations with the Shanghai Institute of Materia Medica, the drug research institute of the Chinese Academy of Sciences.
Its new move mirrors efforts by other major drugmakers to tap into the country's skills in life sciences.
China is rapidly growing in importance for the pharmaceuticals industry -- as a centre of research, production and future sales.
The country is set to become the world's fifth-largest medicine pharmaceuticals market by 2010, with sales nearly doubling to $25 billion from $13 billion in 2005, Boston Consultancy, an independent consulting group, said last year.
In the past Western drugmakers have been wary of investing in China because of a reputation for weak patent protection. But industry executives say patent enforcement is now improving.
© Reuters 2007. All Rights Reserve
May 23, 2007
Two exclusive licensing agreements to commercialize potential treatments for multiple sclerosis and psoriasis have just been completed by UC Davis InnovationAccess and Airmid Inc., a startup company based in Redwood City, Calif.
The agreements cover patents held by UC Davis and UC Irvine on two novel compounds that could be used to treat autoimmune diseases, in which the body's own immune system attacks healthy tissue. The agreements allow Airmid to pursue further testing and commercial development of the compounds.
"Airmid is the latest of the startup companies emerging from the UC campuses -- in this case from both UC Davis and UC Irvine. I'm delighted we've concluded this license with the company, and look forward to their growth and success," said David McGee, executive director of UC Davis InnovationAccess.
"We at Airmid are extremely excited about the prospect of working with the University of California and its world-renowned researchers to bring these potential therapies to the millions of sufferers of autoimmune diseases, who so desperately need safer and more effective treatments," said Airmid CEO George Miljanich.
The first compound, ShK(L5) is a synthetic version of a component of sea anemone venom. It prevents the activity of human immune cells that are implicated in conditions such as multiple sclerosis and is effective in animal models of multiple sclerosis and rheumatoid arthritis.
The second, PAP-1, is derived from a shrub, the common rue. In the laboratory, it can suppress skin inflammation in rats. It could have potential as a treatment for psoriasis.
Both compounds act to block channels that allow potassium ions to flow in or out of cells. These ion channels appear to play an important role in regulating the activity of cells in the immune system and are especially abundant on a type of immune cell implicated in diseases such as multiple sclerosis and psoriasis.
"This could be a completely new mechanism of immune suppression for patients who do not respond to or have side effects from current therapies," said UC Davis' Heike Wulff, assistant professor of medical pharmacology and toxicology.
The compounds were discovered by Wulff and George Chandy, professor of physiology and biophysics at UC Irvine, as a result of work in Chandy's laboratory going back more than two decades. Chandy and Wulff are also among the co-founders of Airmid.
Both compounds have been tested in the laboratory but not yet studied in humans. UC Davis' InnovationAccess unit negotiated the licensing agreements on behalf of both campuses.
Airmid is a privately held pharmaceutical company based in Redwood City, Calif. Airmid is focused on developing its novel potassium ion channel blockers as safer and more effective medicines for a variety of autoimmune diseases that are inadequately treated by current therapies. These diseases include multiple sclerosis, psoriasis, type 1 diabetes and rheumatoid arthritis.
About UC Davis InnovationAccess
UC Davis InnovationAccess actively manages a patent portfolio of 841 inventions reflecting the diversity of the campus's research base, and seeks opportunities to commercialize these via licensing, with 485 currently active licensees. UC Davis has also seen an upsurge in startup companies emerging from campus research and technologies, with nearly 20 companies founded since 2005. The UC Davis InnovationAccess team is comprised of more than 20 professionals with PhDs, JDs, and MBAs with significant private-sector experience.
UC Davis InnovationAccess
Andy Fell, UC Davis News Service, (530) 752-4533, firstname.lastname@example.org
Tuesday, May 08, 2007
MultiCell Technologies Signs Key Formulation and Supply Agreement With Merck KGaA & Co. Spittal/Drau
Agreement Brings MultiCell Closer to Initiation of Phase IIb Clinical Trials
SAN DIEGO, CA--(MARKET WIRE)--Apr 18, 2007 -- MultiCell Technologies, Inc. (OTC BB:MCET.OB - News) has entered into an agreement with Merck KGaA & Co. Spittal/Drau Austria for the formulation and supply of one of the active components of MCT-125, MultiCell's Phase IIb drug for the treatment of chronic fatigue in patients with multiple sclerosis (MS).
About two million people worldwide are afflicted with MS, and an estimated 10,000 new MS cases are diagnosed yearly in the USA. Over 75% of MS sufferers report chronic fatigue and 50% to 60% report chronic fatigue as the worst symptom of their disease. Chronic fatigue severely affects an individual's quality of life. In approximately 30% of MS patients, chronic fatigue is the first symptom, and there is no FDA-approved treatment available for this disease.
In a 138-patient, multi-center, double-blind, placebo-controlled Phase II clinical trial conducted in the United Kingdom, MCT-125 demonstrated efficacy in significantly reducing the levels of fatigue in all three types of MS patients enrolled in the study. MCT-125 demonstrated effectiveness within 4 weeks of the first daily oral dosing. Patients enrolled in the Phase II trial also reported few if any side effects following daily oral dosing of MCT-125. The initial trials were conducted by Amarin Corporation plc who developed the drug as LAX-202.
"We are pleased to have the opportunity to work with an outstanding company like Merck KGaA & Co. Spittal/Drau, and look forward to a long-term relationship. This contract is another key component required for us to commence planned Phase IIb human clinical trials. We are building a solid foundation for the future development of this much need therapeutic, and each new agreement brings this plan closer to reality," stated Dr. Stephen Chang, President and CEO of MultiCell Technologies.
About Merck KGaA & Co. Spittal/Drau
Merck KGaA & Co. Spittal/Drau Austria manufactures bulk and finished pharmaceutical products for third parties, including solid oral dosage forms, semisolids, and liquid products. Merck KGaA & Co. Spittal/Drau is well known for its high quality, excellent customer service, pharmaceutical technology know-how, and optimizing production processes in coordination with its customers. For more information about Merck KGaA & Co. Spittal/Drau Austria see http://www.merck-spittal.at.
About MultiCell Technologies
MultiCell Technologies, Inc. is developing first-in-class drugs based on advanced immune system modulation technologies, and is an integrated biopharmaceutical company committed to the development of breakthrough therapeutics based on a portfolio of therapeutic candidates and patented drug development technologies. MultiCell's drug development program focuses on modulation of the immune system.
MultiCell's therapeutic pipeline includes:
MCT-125 a Phase IIb drug for the treatment of chronic fatigue in MS
MCT-175 for the treatment of relapsing-remitting MS.
MCT-275 for the treatment of juvenile diabetes.
MCT-465 for the treatment of virus infection and cancer.
MCT-475 for the treatment of colorectal cancer.
The Company also holds unique cell-based technology for use in drug discovery screening applications, and is a leading producer of the cell lines needed by the pharmaceutical industry to develop new drugs. For more information about MultiCell Technologies, please visit http://www.multicelltech.com.
Caution Regarding Forward-Looking Statements
Any statements in this press release about MultiCell's expectations, beliefs, plans, objectives, assumptions or future events or performance are not historical facts and are forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"). These statements are often, but not always, made through the use of words or phrases such as "believe," "will," "expect," "anticipate," "estimate," "intend," "plan," "forecast," "could," and "would." Examples of such forward looking statements include statements regarding the timing, design, scope, and anticipated results of our clinical development programs. MultiCell bases these forward-looking statements on current expectations about future events. They involve known and unknown risks, uncertainties and assumptions that may cause actual results, levels of activity, performance or achievements to differ materially from those expressed or implied by any forward-looking statement. Some of the risks, uncertainties and assumptions that could cause actual results to differ materially from estimates or projections in the forward-looking statement include, but are not limited to, the risk that we might not achieve our anticipated clinical development milestones, receive regulatory approval, or successfully commercialize our products as expected, the market for our products will not grow as expected, and the risk that our products will not achieve expectations. For additional information about risks and uncertainties MultiCell faces, see documents MultiCell files with the SEC, including MultiCell's report on Form 10-KSB for the fiscal year ended November 30, 2006, and all our quarterly and other periodic SEC filings. MultiCell claims the protection of the safe harbor for forward-looking statements under the Act and each assume no obligation and expressly disclaim any duty to update any forward-looking statement to reflect events or circumstances after the date of this news release or to reflect the occurrence of subsequent events.
MultiCell Technologies, Inc.
Dr. Stephen Chang, 858.200.0598
Source: Market Wire (Wednesday April 18, 9:00 am ET)