Phase 3 trial results published for two MS oral drugs in development

The New England Journal of Medicine recently published the results of three major studies of oral therapies being tested for treating MS:

• FREEDOMS -- a two-year trial of fingolimod (aka FTY720) that was completed by 1,033 subjects given either high-dose or low-dose fingolimod or placebo
• TRANSFORMS -- a one-year trial of fingolimod that was completed by 1,153 subjects given either high-dose or low-dose fingolimod or Avonex (interferon-1a)
• CLARITY -- a two-year trial of oral cladribine that was completed by 1,184 subjects given either high-dose or low-dose oral cladribine or placebo

Oral cladribine is being developed by Merck Serono and fingolimod is being developed by Novartis. These two drugs are thought to have the best chances to become the first oral disease-modifying drugs approved for treating MS. Their biological effects are different. Fingolimod works to trap immune cells in lymph nodes, preventing them from circulating; it may also have a neuroprotective effect. Cladribine wipes out T and B immune cells and thereby dampens the inflammatory response. Fingolimod is taken on a daily basis, while cladribine is taken over the course of a few weeks in a year.

Each of these trials found the study drug to be significantly superior to placebo (CLARITY and FREEDOMS) or Avonex (TRANSFORMS) in multiple aspects. Both drugs showed a relative reduction in relapse rate (on the order of 40-60%) compared to placebo or Avonex, as well as better MRI results. CLARITY and FREEDOMS also found a beneficial effect of the two drugs on delaying disability progression. However, the results also describe a number of adverse events that occurred during the trials. Most of these were mild or moderate, but there were also some serious adverse events including a few fatalities. Reported adverse events included infections, such as herpes virus infections, cardiac abnormalities, macular edema (swelling of the retina), and various cancers/tumors. In addition, as we've seen with Tysabri, other adverse events may come to light with longer-term usage of these drugs. As the authors of the studies themselves point out, fingolimod and cladribine may have many potential benefits for treating MS, but these benefits need to be weighed against the potential risks.

These results are available to read for FREE on the journal's website (just click on the name of the study in the list above). You can also read an editorial by Dr. William Carroll discussing these studies, or see the press releases provided by Novartis and EMD Serono. I highly encourage anyone who is considering trying cladribine or fingolimod if/when they are approved by the FDA to take advantage of this opportunity to learn more about these drugs.