FDA Approves New Oral Drug for Multiple Sclerosis

People affected by multiple sclerosis (MS) got some good news this week when the Food and Drug Administration (FDA) approved Tecfidera® (dimethyl fumarate) for the treatment of relapsing forms of the disease. MS is a chronic, incurable autoimmune disease of the central nervous system; people with MS experience progressive damage to myelin, the outer covering of nerve cells. The disease disrupts communication between the brain and the body, interfering with movement, sensation, coordination, and thinking. Patients may lose the ability to walk or speak. Most people with MS experiences relapses, in which symptoms increase and functioning may deteriorate; relapses may be followed by periods of remission.

FDA Approval

Tecfidera, formerly called “BG-12,” is made by Biogen Idec, based in Weston, Massachusetts. It comes in capsule form and is taken twice daily.

The FDA approval came after two-phase III clinical trials. The DEFINE trial involved 1,200 people and was designed to test whether the drug reduced the proportion of patients who experienced relapses. Some subjects took two 240 mg doses each day; others took three. After two years, 26 percent and 27 percent of the two treatment groups had experienced relapses, compared to 46 percent of the subjects who took the placebo. Progression of patients’ disability also appeared to have been reduced; 16 percent and 18 percent of patients in the two treatment groups progressed, compared to 27 percent of the patients who received the placebo. Patients in the two treatment groups also had fewer new, growing, or active lesions as revealed in MRIs.

The CONFIRM trial involved 1,400 patients. Two Tecfidera treatment groups received either two or three 240 mg doses per day, while other patients received either a placebo or Copaxone® (glatiramer acetate), an injectable drug made by Teva Pharmaceuticals. Both drugs were compared to the placebo, but the study did not specifically compare Tecfidera to Copaxone.  The average number of relapses in a year was reduced by 44 percent in the twice-daily group and 51 percent in the group taking three doses of Tecfidera, as compared with the patients who took the placebo. Relapses were reduced by 29 percent among the patients who took Copaxone.

Side effects of Tecfidera included nausea, vomiting, diarrhea, and abdominal pain. Decreased white blood cell count also was reported, but there were no reports of opportunistic infections. It is expected that Tecfidera will be used as a first-line treatment for MS. Tecfidera’s safety profile is said to compare favorably with the two oral drugs that the FDA previously approved. Gilenya®, made by Novartis, is the subject of safety concerns because it slows the heart rate. Individuals taking their first dose must be observed for six hours. The FDA required Aubagio to bear a “black box” warning because of risks of potentially fatal liver disease and birth defects.

European Approvals

The Committee for Medicinal Products for Human Use (CHMP), an expert committee of the European Medicines Agency, issued positive opinions on two oral drugs for MS. In addition to Tecfidera, the CHMP approved Aubagio® (teriflunomide), made by Sanofi, for first-line treatment of MS.  Aubagio was not designated a “new active substance” (NAS), however, so its exclusive marketing rights in in the European Union would be limited to three years. The NAS designation protects Tecfidera until 2028.

Pricing

Drugs to treat MS are highly lucrative. The price of Tecfidera has not yet been announced, but the prices of MS drugs have jumped by double digits each year since 2008. And patients pay a premium for the convenience of oral medication. According to the New York Times, the list price of Gilenya is $60,000. Aubagio’s price was discounted to the mid-$40,000 range.