FDA-Approved Medications: New Data
Company: Novartis Pharmaceuticals Corp.
- Oral medication; 0.5 mg capsule taken once daily
- Approved for relapsing forms of MS
Gilenya is the first in a class of immuno-modulatory drugs called “S1P-receptor modulators.” It is similar in structure to a naturally occurring component of cell-surface receptors on white blood cells. (White blood cells are produced by the immune system to fight infection and disease.) Gilenya blocks potentially damaging T cells from leaving lymph nodes, lowering their number in the blood and tissues. It may reduce damage to the CNS and enhance the repair of damaged nerves within the brain and spinal cord.
Although Gilenya was approved for relapsing-remitting MS (RRMS) in 2010, clinical trials have continued to evaluate its role in MS. The 36-month INFORMS trial evaluated the effect of Gilenya relative to placebo on delaying the time to sustained disability progression in patients with PPMS. As there is presently no FDA-approved medicine for PPMS, this was an important study for the field.
The enrollment of 969 PPMS patients into the INFORMS trial was completed in 2011, and the trial’s data analysis was completed in 2014. Novartis announced in December 2014 that unfortunately, the primary outcome of the study was not met. Gilenya did not show a significant difference from placebo on a combination of disability measures.
A novel, primary-composite disability endpoint was used in the trial, based on the increase in disability as measured by the Expanded Disability Status Scale (EDSS), the 25-Foot Timed-Walk Test (T25FW), and the 9-Hole Peg Test (9-HPT). Other key endpoints were the formation of new lesions and percentage of brain-volume change (PBVC), or brain atrophy (the shrinking or reduction of brain volume). Detailed results of the trial were presented in spring 2015. Gilenya did not prevent the accumulation of disability in patients with PPMS any greater than placebo. Furthermore, PBVC did not differ between the Gilenya and placebo groups.
Unsurprisingly, given this agent’s success in reducing relapses and new MRI lesions in RRMS patients, there were fewer new MRI lesions seen in the Gilenya-treated patients. The safety results were generally consistent with this medication in prior MS trials. It is certainly disappointing that Gilenya did not significantly slow disease progression in PPMS. These findings, like those of Tysabri in SPMS, have important implications for the understanding of progressive disease, and will no doubt allow researchers to refine how this is studied moving forward.
Another ongoing Gilenya clinical trial is a Study Evaluating Safety and Efficacy of Two Doses of Fingolimod Versus Copaxone.3 This 12-month trial will compare the marketed dose of Gilenya with one-half this dose, using Copaxone as a comparison, on annual MS relapses and several MRI measures of disease. The goal of this study, which was required by the FDA, is to assess if a lower dose of this medication may be equally effective at reducing the number of relapses in patients with relapsing forms of MS. This study is expected to report data in 2016.