Gilenya NDA covers highly active relapsing-remitting MS and rapidly evolving severe relapsing-remitting MS.
While the EMA’s Committee for Medicinal Products for Human Use (CHMP) doled out negative opinions for Biogen Idec’s and Merck KGaA’s multiple sclerosis (MS) drugs, Novartis won the committee’s approval for Gilenya. CHMP recommended that Gilenya 0.5 mg daily could be used as a disease-modifying therapy for patients with highly active relapsing-remitting MS despite treatment with beta interferon or in patients with rapidly evolving severe relapsing-remitting MS.
CHMP, however, recommended against the sanction of Biogen Idec’s Fampyra® tablets as a therapy to help improve walking ability. It also reiterated a previous negative opinion on Merck’s Cladribine tablets, which are designed to be a short-course, disease-modifying drug.
Novartis points out that CHMP’s decision on Gilenya was based on the largest clinical trial program submitted to date for a new MS medication. It included data from clinical studies showing significant efficacy in reducing relapses, the risk of disability progression, and the number of brain lesions detected by MRI.
Gilenya, licensed from Mitsubishi Tanabe Pharma, if approved would be the first in a new class of drugs called sphingosine 1-phosphate receptor (S1PR) modulators. In MS the immune system damages the covering that protects nerve fibers in the central nervous system (CNS). Gilenya is thought to work by reducing the immune system’s attack on the CNS by retaining lymphocytes in the lymph nodes, Novartis explains.
This prevents the white blood cells from reaching the CNS, where they could potentially attack the protective covering around the nerve fibers, resulting in less inflammatory damage to the nerve cells.
The white blood cell retention is reversible if Gilenya treatment is stopped, the company adds.
The EU application included data showing Gilenya 0.5 mg reduced relapses by 52% at one year compared with interferon beta-1a IM (Biogen Idec’s Avonex®). Data from a two-year placebo-controlled study showed a reduction in the risk of disability progression among Gilenya patients (30% reduction confirmed at three-month follow-up). In clinical studies, treatment with Gilenya also resulted in statistically significant reductions in brain lesion activity as measured by MRI.
Gilenya has been studied in more than 4,000 MS patients. The most common side effects are back pain, cough, diarrhea, headache, influenza, and liver enzyme elevations. Other Gilenya-related side effects include transient, generally asymptomatic heart rate reduction and atrioventricular block upon treatment initiation, mild blood pressure increase, macular edema, and mild bronchoconstriction.
The rates of infections overall, including serious infections, were comparable among treatment groups, although a slight increase in lower respiratory tract infections (primarily bronchitis) was seen in patients treated with Gilenya. The number of malignancies reported across the clinical trial program was small, with comparable rates between the Gilenya and control groups, Novartis reports.