Research News
Initial Trial Results for FTY720 are Encouraging
Data from Phase II studies of FTY720 (fingolimod) for individuals with relapsing-remitting MS (RRMS) show encouraging results at 18 months. FTY720 is an investigational drug for MS that is given orally (by mouth) once per day. Novartis, the company that developed and is testing the drug, presented the data at the American Academy of Neurology's (AAN) Annual Meeting. According to Novartis, the study's two treatment arms (taking 1.25 mg and 5 mg daily) experienced more than a 50 percent reduction in their annualized relapse rate compared to placebo.
These results were initially shown during the first six months of the study, and were maintained through the subsequent 12-month extension (totaling 18 months). Study participants who switched from placebo to one of the treatment arms (receiving FTY720 at either dose) after six months, also experienced the same reduction in relapse rate.
Magnetic Resonance Imaging (MRI) scans were performed in a subgroup of patients. Consistent with what was seen with the MRI scans after six months, the vast majority of these study participants were reported to be free from lesions showing active inflammation after 18 months on the drug.
Adverse events during the first six months of treatment included: first-dose heart rate reduction; increase in blood pressure; alteration in liver function; and mild increase in airway resistance. These did not appear to progress with continued dosing beyond the initial six months. In patients treated for up to 18 months, the most commonly reported adverse events were non-serious infections (colds, influenza) and headache. All participants in the extension study are now on the lower, 1.25 mg dose, since the higher, 5 mg dose, had an increased rate of adverse events, while both doses were equally effective in reducing disease activity.
The drug is believed to work by lowering the number of activated T-cells circulating to the blood stream and central nervous system. This in turn reduces inflammation and myelin damage in the brain and spinal cord. A two-year, Phase III study called "FREEDOMS" (Fingolimod Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis) will include more than 1,000 participants. The study has begun enrolling in Europe; Novartis is currently discussing Phase III trials in the United States with the FDA.
MBP8298 Shows Promise in Treating Subgroup of MS Patients
MBP8298 is an investigational treatment being studied for safety and effectiveness in a subgroup of individuals with secondary-progressive MS (SPMS). The drug shows potential when used for SPMS patients who possess the HLA-DR2 or HLA-DR4 immune response genes. This "responder group" is believed to comprise up to 75 percent of the MS population.
Developed and studied by BioMS, MBP8298 is administered intravenously every six months. According to the company's data presented at the AAN's Annual Meeting, this treatment showed a five-year delay of disease progression for individuals with SPMS. Treatment and follow-up of patients from a phase II clinical study demonstrated that those within the responder group (having the HLA-DR2 or HLA-DR4 immune response genes) had a median time to disease progression (worsening) of 78 months (six-and-a-half years) compared to 18 months (one-and-a-half years) for patients who received a placebo. Disease progression was measured according to the Expanded Disability Status Scale (EDSS). These findings were based on the long-term follow-up treatment and assessment of 20 progressive MS patients with the response genes mentioned.
BioMS is presently enrolling approximately 553 individuals with SPMS in Canada, the United Kingdom, and Sweden. The Phase II/III study will evaluate a 500 mg dose of MBP8298 administrated intravenously every six months, compared to a placebo, over a two-year period. The primary clinical endpoint for the trial will be time to progression, as measured by the EDSS. To date, the trial has successfully completed three safety reviews by its independent Data Safety Monitoring Board.
MBP8298 is a synthetic peptide that consists of 17 amino acids, which are linked in a sequence identical to that of a portion of human myelin basic protein (MBP). More than 26 years of research have gone into this investigational treatment. MS is believed to be an autoimmune disease, caused by an immune attack against normal components of the central nervous system. MBP8298 is a molecular replicate of the site of attack for patients with the HLA haplotypes DR-2 or DR-4. This drug has been designed to work as a decoy for the immune system T-cells which damage the CNS in this subgroup of MS patients.
FDA Advisory Committee Supports Tysabri's Return to Marketplace; Review Period Extended by 90 Days
Following the Food and Drug Administration's (FDA) Peripheral and Central Nervous System Drugs Advisory Committee Meeting on March 7 and 8, 2006, members of the Committee decided that Tysabri's effectiveness outweighs the potential for serious adverse events, recommending its return to the marketplace for treating individuals with the relapsing-remitting form of multiple sclerosis (MS).
Manufactured and marketed by Biogen Idec and Elan Corporation, Tysabri¨ (natalizumab) is an investigational drug being studied for the treatment of MS. It was given early approval in November 2004, but was voluntarily suspended three months later after progressive multifocal leukoencephalopathy (PML), an often-fatal brain disorder, was confirmed in three patients who had taken the drug.
Although the Advisory Committee's recommendation does not guarantee that Tysabri will be approved, the FDA typically follows the recommendation of its Advisory Committees. According to an FDA spokesperson, a risk-management plan for patients is being planned and a patient registry may also be set-up; additional patient-safety studies will be conducted as well.
Two weeks after the March 2006 Advisory Committee meeting, the FDA posted a statement on the review time for Tysabri. According to the statement, the FDA had extended the regulatory review period up to 90 days, allowing the FDA more time to review the new information supporting the reintroduction of Tysabri for the treatment of MS. The agency hopes to have completed the review of new information before the end of the 90-day extension period.
Serono Submits New Rebif Formulation for FDA Approval
On April 4, 2006, Serono announced that it has submitted an application to the FDA (as well as to the European Medicines Agency) for a new formulation of Rebif¨ (interferon beta-1a). This drug is presently approved for the treatment of relapsing-remitting MS (RRMS) and is given via subcutaneous injections three times per week.
According to Serono, this new formulation results in a substantial improvement in overall tolerability, including injection site reactions. Additionally, trial data show that the incidence of antibody formation with this new formulation is reduced. Serono plans to present this data at a major medical conference in the second half of this year.
— Susan Wells Courtney
