According to Novartis, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has confirmed a positive benefit-risk profile for their once-a-day orally administered drug Gilenya (fingolimod).

In agreement with the CHMP, the company has updated their E.U. product information after the Article 20 review the EMA announced in January 2012, in order to offer further guidance to healthcare providers who want to initiate using Gilenya in MS patients. In the E.U., Gilenya is approved for the treatment of individuals with highly active relapsing-remitting MS, regardless of treatment with beta interferon, or in patients with rapidly evolving severe relapsing-remitting MS.

Gilenya is the first in a new class of sphingosine 1-phosphate receptor (S1PR) modulating compounds and has demonstrated superior efficacy over Avonex (interferon-beta-1a IM), a commonly prescribed treatment. In a pivotal head-to-head trial in patients with relapsing- remitting multiple sclerosis at one year, Gilenya achieved both its primary and secondary endpoints, i.e. a 52% relative reduction of the yearly relapse rate and a 40% relative reduction in the rate of brain atrophy.

A recent sub-analysis at one year revealed that in comparison to interferon-beta-1a (IM), Gilenya achieved a 61% relative reduction in the rate of yearly relapses in patient subgroups with highly active relapsing-remitting MS patients who previously received interferon therapy.

Gilenya has no label restrictions specific to treatment duration and was generally well tolerated during clinical trials with a manageable safety profile. Since February 2012, over 36,000 patients have been treated with Gilenya in clinical trials and in the post-marketing setting, which confirms Gilenya’s long- term effectiveness and safety profile. 2,400 patients have been taking the drug for longer than two years.

The most common adverse events reported were cough, diarrhea, headache, liver enzyme elevations and back pain, whilst other side effects included a mild increase in blood pressure, transient, generally asymptomatic, heart rate reduction and atrioventricular block upon treatment initiation, macular edema, and mild bronchoconstriction.

Overall, the rates of infections, including serious events were similar in all treatment groups. However, patients treated with Gilenya reported a slightly higher rate of respiratory tract infections that consisted mainly of bronchitis. There were only a small number of reported malignancies in the clinical trial, with similar rates between the Gilenya and control groups.

All MS patients who start Gilenya therapy in the E.U. should have an electrocardiogram (ECG) and a blood pressure measurement before taking the first dose and after the six-hour first-dose monitoring period, in addition to having hourly measurements of their blood pressure and heart rate taken during this period. It is also recommended that patients’ with symptomatic bradycardia (low heart rate) receive continuous ECG monitoring for at least six hours after taking the first dose, with those who had ECG abnormalities during the 6-hour monitoring period requiring extended monitoring, as well as those who had very low or their lowest measured heart rate at the six-hour time point.

The recommended label update in the E.U. also warns that Gilenya should not be used in patients who may be less tolerant of or tend to have a higher risk of developing a substantially slower or abnormal heart rate, due to certain underlying conditions or other medications taken at the same time.

Previous clinical trials have revealed insufficient knowledge about using Gilenya in such patients, but if these patients are to be treated, they would require overnight monitoring.

Patients who are already taking Gilenya are not affected by the new first-dose observation recommendations. However, should therapy be interrupted for longer than two weeks, patients should undergo the new recommended monitoring upon re-initiation of the treatment. Patients should not make any changes to any medications, including Gilenya, without first consulting with their doctor.

David Epstein, Division Head of Novartis Pharmaceuticals declares:

“We believe that Gilenya is a valuable treatment option for many patients with relapsing remitting MS, and we welcome the confirmation of the positive benefit-risk profile of the drug which also supports our continued belief of the blockbuster potential of Gilenya. MS is a devastating chronic disease that affects more than 2.1 million people worldwide, and patients need effective treatment options.”

The EU will review the CHMP labeling recommendations, with a final decision expected in June 2012. In terms of any changes to the EU product information, Novartis will notify EU physicians via a Direct Healthcare Provider Communication (DHPC) by end of April 2012.

For the Gilenya information site, click here

Written By Petra Rattue