Multiple Sclerosis Drug Pipeline Expanding

Minneapolis—When the US Food and Drug Administration (FDA) approved interferon beta-1b, a biotechnology product, in 1993, the treatment approach regarding multiple sclerosis (MS) changed, according to Gary M. Owens, MD, president of Gary Owens Associates in Glen Mills, Pennsylvania. Recently, there has been another shift in managing MS. There are now 5 disease-modifying therapies (DMTs) available, and the FDA approved fingolimod last year as the first oral agent intended for MS. In addition, several more agents may be approved soon, creating coverage and management issues for health plans and pharmacists. Dr. Owens spoke during a satellite symposium at the AMCP meeting titled Optimizing New and Emerging Therapies for Treatment and Symptom Management of Multiple Sclerosis in Managed Care. He said the following therapies are now in late-stage trials: cladrabine, dimethyl fumarate, laquinimod, alemtuzumab, terifulnomide, and new formulations of existing disease modifiers. Bruce L. Hughes, MD, associate professor in neurology at Des Moines University College of Medicine in Des Moines, Iowa, said MS is characterized by a focal disorder in the central nervous system. Approximately 400,000 people in the United States have MS, and there are 2 or 3 times more women than men with MS. Dr. Hughes said the cause of MS is unknown. However, the risk of developing MS occurs in the first 15 years of life, although people do not develop MS until years or decades later. The peak onset of MS is at 31 years of age, with a typical range of 18 to 55 years. There are 4 clinical subtypes of MS: relapsing-remitting multiple sclerosis (RRMS), secondary progressive, primary progressive, and progressive-relapsing. Dr. Hughes said 85% of patients begin with RRMS and then may progress to another type of MS. When treating MS, healthcare professionals have numerous drug options that are FDA approved: interferon beta-1b, interferon beta-1a, glatiramer acetate, mitozantrone, natalizumab, and fingolimod. Dr. Hughes said there is a 2-pronged approach to managing MS: treating the symptoms of MS and then treating the disease itself. “We’re getting good at prevention [of MS], but we’re bad at restoration of the central nervous system,” Dr. Hughes said. Dr. Hughes discussed a few placebo-controlled, randomized trials of first-line DMTs for patients with RRMS. For instance, interferon beta-1a administered through intramuscular injection reduced the relapse rate by 18%; interferon beta-1a administered subcutaneously reduced the relapse rate by between 27% and 32%; interferon beta-1b administered subcutaneously reduced the relapse rate by 34%; and glatiramer acetate reduced the relapse rate by 29%. Mitoxantrone and natalizumab, second-line DMTs, also reduced relapse rates during placebo-controlled, randomized trials. Dr. Hughes then spoke about the FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis) study, a 24-month, phase 3 trial of 1272 patients with MS. The authors found that 0.5 mg and 1.25 mg of fingolimod were significantly superior in reducing the annualized relapse rate of MS compared with placebo (P<.001 in both comparisons). Both doses of fingolimod were statistically superior compared with placebo in reducing disability progression (P=.024 and P=.017 for 0.5 mg and 1.25 mg fingolimod, respectively). In addition, the phase 3 TRANSFORMS (Trial Assessing Injectable Interferon vs FTY720 Oral in RRMS) study found both doses of fingolimod significantly reduced the annualized relapse rate at 12 months compared with interferon beta-1a (P<.001 for both comparisons). However, the FDA approved only 0.5 mg of fingolimod due to toxicity issues associated with 1.25 mg of the agent.