Ever since the very first Betaseron needles appeared in 1993, the one question I have heard more than any other is “when will we have a pill for MS?” Now that that day has arrived I thought I would update you on what is now available and what is expected in the next year or so.
As most of you know, there is already one pill on the market for relapsing MS. It was approved by the FDA in September, 2010 and is called fingolimod, brand name Gilenya, made by Novartis. It is taken once a day and in the research studies appeared to be quite effective. Relapses were reduced by >50% compared to both placebo and to beta-interferon, and disability progression was also reduced relative to placebo (but not to interferon). New lesions on MRI were also reduced.
The drug does have side effects, of course, and has not been in widespread use for as long as some of the others. In the research trials it was tested at 2 doses, 1.25 mg/day(high dose) and 0.5 mg/day(low dose). The low dose did as well as the high dose as far as treating the MS, but had fewer side effects, and so only the low dose was approved by the FDA.
Gilenya tends to cause slowing of the heart rate when first given, so patients have heart monitoring for 6 hours after the first dose. It can also cause swelling of the macula in the back of the eye. This is reversible but monitoring by an eye doctor is required. Other problems include low white blood counts, high blood pressure, and liver inflammation. Also, a patient recently died shortly after his first dose of Gilenya. Autopsy results are not yet known, but it may be that more extensive cardiac monitoring and/or screening will be required in the future.
In summary, the drug is well tolerated by most, and it does seem to be effective, but there are certainly enough safety concerns to warrant caution in its use.
So what’s on the horizon? The most exciting drug is called BG-12 (aka dimethyl fumarate). This is a pill made by Biogen (Avonex, Tysabri) which is taken 2 or 3 times a day. It also seems to be quite effective, reducing the relapse rate by about 51% and the rate of disability progression by 24%. It did significantly better than Copaxone in the head to head trial as well. How does it work? That’s not entirely known yet but it seems to reduce inflammation and protect both nerve cells and myelin in the brain.
So far the safety profile seems good, but about 38% of patients have had facial flushing and some have had gastrointestinal symptoms. Because this drug is approved in Europe for psoriasis, there is a longer period of safety data available and so far no serious effects have turned up. The timetable for possible FDA approval is unclear, as it is with all of these, but I will keep you posted.
Two other oral medications are currently being studied as well, teriflunomide and laquinimod. Teriflunomide (Aubagio) is the active metabolite of leflunomide (Arava) which is approved for use in rheumatoid arthritis, another autoimmune disease. It is made by Genzyme/Sanofi and has already been submitted to the FDA for approval. It prevents proliferation of T-lymphocytes, inflammatory cells which cause the myelin damage in the brain. Studies so far show that it reduces relapses by 31%, disability progression by 30%. In the trials so far the side effects have been very mild, but Arava, which is similar, has been associated with rare cases of fatal liver failure and at least one case of PML in a patient with lupus. In addition, it is a type of medication known to have the ability to cause birth defects, so great care will be needed treating patients with childbearing potential.
Laqinimod, made by Teva, has shown somewhat more modest effects compared to the two drugs above, although the safety and tolerability have been good so far. It may have a neuroprotective effect on the brain. Relapse rate was down by 23% and rate of progression by 36%. It also slowed brain shrinkage by 33%. The dose is 0.6 mg daily.
These new drugs will present a challenge to all of us. Who should stay with their current drug and who should consider one of these newer ones? What about Tysabri patients? Stay tuned, I will address these issues soon.