Multiple Sclerosis Relapse Rate Reduced By Nearly Half With Use of Two New Drugs

Cladribine and fingolimod, two new oral drugs, have been shown to decrease the relapse rate in people who suffer from multiple sclerosis. The drugs could become the first treatments for the disease that does not require regular injections or infusions, if they gain approval by the U.S. Food and Drug Administration (FDA).

Multiple sclerosis (MS) is a chronic and frequently disabling disease that attacks the central nervous system. According to the National Multiple Sclerosis Society, the condition affects about 400,000 Americans and is the most frequent cause of neurological disability other than trauma in people from ages 20 to 50. Symptoms vary among patients and can range from mild to severe and may cause numbness of the limbs, paralysis and even loss of vision. The progression and severity of the disease are unpredictable.

Relapsing/Remitting Multiple Sclerosis (RRMS) is one of four recognized forms of MS. However, approximately 85 percent of people presenting with Multiple Sclerosis are first diagnosed with RRMS. This form of MS is characterized by relapses that may last for days, weeks or even months, during which new symptoms can appear and old symptoms may resurface or worsen. These relapses are followed by periods of remission in which the patient fully or partially recovers from the effects that occur during relapse periods. Recovery may be gradual or practically instantaneous.

In the Phase III study of 1,200 patients with the RRMS, approximately 80 percent of MS patients who took the drug cladribine remained relapse-free for two years compared to only 61 percent of those participants given a placebo. Side effects of cladribine were mild and included headaches, colds, flu, and nausea. The patients were followed for almost two years and monitored with the use of MRI scans. The study participants all had been living with MS for an average of six to seven years, and suffered from at least one relapse in the year prior to the study.

During the study, led by Gavin Giovannoni, M.D., of the Barts and London School of Medicine and Dentistry, participants received either four courses of low-dose cladribine tablets, six courses of higher-dose cladribine tablets, or a placebo. According to Giovannoni, this means, “that individuals with MS only have to take tablets for 8 to 20 days a year. That should improve compliance.”

The study participants who received cladribine were found to be 55 to 58 percent less likely to suffer from a relapse within a year than those given a placebo. In addition, the cladribine recipients were 33 percent less likely to experience deterioration in their disabilities, such as increase in the difficulties of walking. Based on MRI scans, participants taking cladribine were also found to have considerably brain and spinal cord lesions that are typical for MS patients.

Cladribine is already licensed and marketed under the name Leustatin for the treatment of leukemia and is believed to work in the fight against MS by suppressing the autoimmune responses thought to cause the disease. Merck Serono plans to apply for FDA approval within months.

In another successful phase III study of over 1,200 patients with RRMS, 80 to 84 percent of MS patients who were given daily dosages of the drug fingolimod remained relapse-free after one year in comparison to only 67 percent of study participants who received Avonex, a typical injectable drug used to treat MS. Participants in this study had been living with MS for an average of seven years, and all had suffered from an average of two relapses within two years prior to the study. Jeffrey Cohen, M.D., of the Cleveland Clinic, led the study.

Participants taking fingolimod were found to be 38 to 52 percent less likely to suffer from a relapse within a year and also experienced fewer lesions than participants who received the Avonex injections. The length of the study was insufficient to allow conclusions to be drawn on fingolimod’s effects on disabilities. The most common side effects experienced included, headache, head colds and fatigue. However, eight cases of skin cancer as well as four cases of breast cancer did occur and it remains unclear as to whether or not fingolimod was responsible for these events.

Fingolimod also suppresses the autoimmune responses thought to cause MS. There are two other ongoing studies of fingolimod for which results are expected within a few months. The maker of the drug, Novartis, anticipates application to the FDA for approval by the end of this year.

The phase III studies for both cladribine and fingolimod were presented at the annual meeting of the American Academy of Neurology. Because both drugs suppress the autoimmune responses, concerns remain regarding the safety of long-term use, as T cells are necessary for fighting infections, and particularly viral infections. Cladribine damages the ability of the T cells to reproduce and proliferate while fingolimod locks T cells inside the lymph nodes, preventing them from traveling through the bloodstream and into the brain and spinal cord. More studies of both drugs will be required to determine safe measures for their use.