First Oral Disease-Modifying Therapy Approved in Canada (Gilenya®)
On March 9, 2011, Health Canada approved Gilenya® (fingolimod) capsules, the first oral disease-modifying therapy developed for relapsing-remitting MS.
Gilenya (prounounced Jil-EN-ee-ah) has been approved for use in people who have tried one or more MS therapies, but are unresponsive or intolerant to them. It is indicated for use as a monotherapy for the treatment of people with the relapsing-remitting form of MS to reduce the frequency of clinical exacerbations (relapses) and to delay the progression of physical disability. Health Canada’s approval is based on results from two large-scale placebo-controlled clinical trials, each with over 1,200 participants.
Gilenya is a new class of medication called a sphingosine 1-phosphate receptor modulator, which is believed to act by retaining certain white blood cells (lymphocytes) in the lymph nodes, thereby preventing those cells from crossing the blood-brain barrier into the central nervous system (CNS). Preventing the entry of these cells into the CNS reduces inflammatory damage to the nerve cells.
The medication will be available in Canadian pharmacies by April 1, 2011.
According to Novartis, the company will apply immediately to private/employer health care programs to have Gilenya covered. It is expected that most private insurance plans will cover Gilenya. The company will also apply to the Common Drug Review (CDR) and Conseil du Médicament (Québec) within the next few weeks. The Common Drug Review advises whether or not a drug is cost effective and should be covered by public drug programs. Provincial drug programs then use this information in making their decisions. Depending on the province, this can take anywhere from 8-24 months from initial submission to final recommendation. It should be noted that Quebec conducts its own review, independent of the CDR.
Potential Benefits and Risks:
Gilenya has a well-studied safety and tolerability profile. It has been studied in over 4,000 MS patients around the world. Some are in their seventh year of treatment.
Health Canada’s approval is based on results from two major Phase III trials. Each study was double-blind and controlled in design meaning patients and evaluating physicians did not know whether they were on the Gilenya or the comparison drug. One trial involving 1,272 individuals with relapsing-remitting MS (FREEDOMS) lasted two years and compared Gilenya to a placebo (New England Journal of Medicine, January 20, 2010). Over two years, Gilenya was able to significantly reduce relapse rates (the primary endpoint of the study) and slow disability progression (a secondary endpoint) compared to those on inactive placebo. Gilenya reduced relapses by 54% and reduced the risk of disability progression by 30% as compared to placebo. Gilenya also reduced brain tissue injury and brain atrophy as measured by MRI.
The second trial, a one-year trial with 1,292 individuals with relapsing-remitting MS (TRANSFORMS study), compared Gilenya with Avonex® (interferon beta-1a). In the study, Gilenya (at a dose of 0.5mg) reduced relapses by 52% as compared with Avonex. It also reduced disease activity as measured by the number of new and newly enlarged T2 lesions on MRI scans as compared with Avonex (1.2. v/s 2.6, respectively at one year), and reduced brain lesion activity as measured by MRI.
While benefit of the therapy has been demonstrated, the risks are greater than for those on beta-interferons or glatiramer acetate. The MS Society will closely monitor all information with respect to Gilenya’s safety and efficacy profile and will provide updates as required.
In both studies, two doses of Gilenya were investigated (0.5mg and1.25 mg). The studies determined that the lower dose of Gilenya (0.5mg) was better tolerated and was just as effective. For this reason, only the safer low dose (0.5mg) of Gilenya has been approved for use.
A few participants experienced a transient reduction in heart rate and partial blockage of heart conduction (second-degree atrioventricular conduction block) after the first dose of the medication which normalized spontaneously after several hours. During the second month of therapy, a slight increase in blood pressure was reported in some of the participants. Occasional instances of macular edema (swelling of the center of the retina inside the eye) were seen especially in those on the higher dose of Gilenya in both studies. Skin cancers were reported more frequently in those on Gilenya in the one-year TRANSFORMS study, but not in the longer 2 year FREEDOMS study. Malignancies were more common in those on placebo in the two-year FREEDOMS study.
Elevations in liver enzymes, without accompanying symptoms, were common in those receiving Gilenya. In both studies, a small number of herpes infections occurred such as shingles and there were two deaths from herpes infections that occurred in the TRANSFORMS trial in people taking the higher (not approved) dose of Gilenya.
The safety of Gilenya during pregnancy is uncertain but the drug could potentially cause birth defects.
The long-term safety of Gilenya is unknown at this time. Other Phase III clinical trials of Gilenya, including one involving people with primary progressive MS, are still under way, as are extension studies involving those who have already completed trials.
The MS Society of Canada will closely watch these and other post-approval studies for further information on the long-term safety and efficacy of this oral drug.