An experimental oral medication for people with multiple sclerosis has shown positive results in a second phase clinical trial that took place in Europe recently. The trial's findings were released at a European neurology conference in June.1
New Oral Therapy?
The drug is called temsirolimus (tem-sir-AH-lih-mus). It belongs to a class of drugs known as rapamycin analogs,2 and works by blocking an enzyme used to control a cell's life cycle; the drug prevents cells from dividing into new cells. As such, it is also being tested as a therapy for certain cancers.3
Additionally, temsirolimus works by blocking the build-up of T cells—immune system cells that are believed to play a role in the onset of MS by attacking parts of the central nervous system. Specifically, temsirolimus blocks T cells called into action by a so-called messenger protein known as interleukin 2.
"The efficacy and safety of temsirolimus were evaluated in patients with clinically definite relapsing-remitting MS or secondary progressive MS with relapses," wrote Ludwig Kappos, MD, a neurologist at University Hospital in Basel, Switzerland, and his colleagues who released their study results at the annual meeting of the European Neurological Society.
Nine-Month Treatment Schedule
For the Phase 2 randomized, double-blind, controlled trial, nearly 300 patients aged 19 to 57 years old were enrolled. Patients were eligible for the trial if they had certain minimum disability scores and at least one documented relapse in the preceding 12 months.
Each patient was then assigned at random to receive three doses of temsirolimus (2, 4, or 8 mg once per day) or a group receiving a placebo. Treatment continued for a total of nine months.
During the trial, investigators performed magnetic resonance imaging (MRI) scans of each patient to locate any brain lesions. The objective was to determine the number of new lesions that had formed by the time the study ended. Other data collected on the patients included total brain volume, their total number of relapses during the study, and their average level of disability.
Highest Dose was the Most Effective
By the end of the trial, Kappos and his team found that those patients receiving the 8-milligram dose of temsirolimus had achieved significant reductions in the number of new lesions, based on their MRI exams. On average, patients in this group had nearly 50% fewer lesions at the end of the 9-month trial period, the investigators reported, compared with those in the group given only the placebo.
Brain atrophy decreased, and there was a 51% reduction in the number of new relapses in the treatment group compared to those taking the placebo. "Dose-related trends in percentage of relapse-free patients and progression of disability were also noted," Kappos and his colleagues wrote.
Serious side effects occurred during the trial, but happened about as often across all the treatment groups. The most commonly reported side effects (by those in the group given the 8 mg-dose) included mouth ulcerations (aphthous stomatitis), high blood lipids, rashes, and menstrual abnormalities.
"An oral, 8-mg dose of temsirolimus administered over 9 months in patients with relapsing forms of MS resulted in significant beneficial effects on the incidence of new enhancing MRI lesions and number of relapses, with an acceptable risk/benefit profile," Kappos and his team concluded.
1. Kappos L, Barkhof F, Desmet A et al. The effect of oral temsirolimus on new magnetic resonance imaging scan lesions, brain atrophy, and the number of relapses in multiple sclerosis: results from a randomized, controlled clinical trial. 15th Meeting of the European Neurological Society. 2005 June 18 June 22. Vienna, Austria.
2. National Cancer Institute. Temsirolimus.
3. Wyeth Pharmaceuticals. News Release. FDA grants fast track status to temsirolimus, an investigational drug for first-line treatment of patients with advanced renal cell carcinoma.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
