Allison Gandey

October 29, 2010

October 29, 2010 (Gothenburg, Sweden) — The first oral treatment for multiple sclerosis (MS) is entering the market and is changing the prescribing landscape. Many specialists anticipate an excited push by patients to trade injections for tablets, yet many remain wary of the long-term safety and say they will be slow to switch patients.

During a news conference here at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Jon Lycke, MD, from Sahlgrenska University in Sweden, told reporters that he plans to leave his patients, who are on injections and doing well, on their current standard medications.

"Tablets are much easier and more convenient for patients, so I think there will be an urge by some to switch, but we still have a long way to go, and I'd like my patients who are doing well to remain on their injections," he says.

Dr. Ludwig Kappos

Ludwig Kappos, MD, from University Hospital in Basel, Switzerland, told reporters that although new options are exciting, the decision-making process isn't getting any easier. "There are advantages and disadvantages, and we will have to weigh these carefully against the evolving side effect profile of new drugs."

In a Medscape expert video commentary, Andrew Wilner, MD, from Lawrence and Memorial Hospital in New London, Connecticut, said, "This is a total game changer." There's no question, he added, that the biggest news at this meeting is the new drugs that are available for the treatment of MS.

Fingolimod (Gilenya, Novartis) is the first oral agent approved in the United States. It acts as a superagonist to sphingosine-1-phosphate receptors on the surface of thymocytes and lymphocytes, reducing the overall number of circulating lymphocytes available to mount an autoimmune reaction to the myelin sheath surrounding axons in MS.

Novartis announced earlier this month the average annual cost of fingolimod will be US $48,000.

Cladribine (Merck Serono) was also in the race for first oral agent for the treatment of MS. Although the drug was previously granted fast-track status by the US Food and Drug Administration in 2006, the agency refused to file the company's new drug application in 2009 amid speculation about tabulation errors and potential safety concerns. Cladribine was recently approved in Russia and Australia but received a negative opinion from European regulators in September, a decision the company plans to appeal.

Other oral MS treatments in development include laquinimod (Teva), teriflunomide (Sanofi-Aventis), and BG-12 (Biogen).

This is a total game changer.

During an interview with Medscape Medical News, Stanley Cohan, MD, medical director at the Providence Multiple Sclerosis Center in Portland, Oregon, said he also plans to leave most of his patients on injections. "I definitely won't consider fingolimod a first-line agent," he said.

"It is very unclear at this point when people should be started on this drug," Dr. Wilner agreed. "It has an annualized relapse rate approximately half that of the interferons."

Sidney Spector, MD, from the Veterans Affairs Medical in Phoenix, Arizona, said that he doesn't believe fingolimod provides any great benefit. "Convenience is the main advantage for the patient," he suggested. "Some people will demand it, but this will have to be weighed carefully against the adverse events. I think many neurologists will choose to wait and see."

Enthusiasm Tempered by Vigilance

Enthusiasm, Dr. Spector added, should be tempered by vigilance about the potential risks of the new immunomodulator.

These concerns were echoed In September at the American Neurological Association annual meeting. Peter Calabresi, MD, a FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) trial investigator, acknowledged the strong efficacy numbers for fingolimod but also its safety signals.

Dr. Calabresi at Johns Hopkins in Baltimore, Maryland, is principal investigator of the original phase 3 trial, also known as FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis, which has US Food and Drug Administration (FDA)-mandated safety measures. The new postmarketing phase 4 study is anticipated to include about 6000 patients.

Patients will have to be closely monitored.

"My personal feeling is that physicians should have access to this drug, but patients will have to be closely monitored," he said during an interview. "I am concerned about the dermatological effects, malignancies, and infections."

In another recent trial of fingolimod, 2 patients died of herpetic infections. The Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS) showed a benefit with fingolimod against interferon beta and against placebo, but the adverse events were significant. One patient died of disseminated primary varicella zoster and another of herpes simplex encephalitis.

One problem, Dr. Calabresi said, is that neurologists may not feel entirely equipped to closely monitor the entire body to assess complications of the skin, cancers, and infections. Still, he says, "If you prescribe it, you're responsible for it." And he calls on clinicians to remain vigilant.

Clinical trials of fingolimod were supported by Novartis Pharmaceuticals. Dr. Calabresi has received financial support from the company. The other commentators have disclosed no relevant financial relationships.

26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). October 13-16, 2010.

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