Novartis adds cardiovascular warning to Gilenya label

Novartis has added a requirement for cardiovascular monitoring to the US labelling for Gilenya, its oral drug for multiple sclerosis, while the EMA has called for similar changes in Europe.

The change to the  drug's US labelling comes in the wake of an FDA review of its safety prompted by the sudden death of patient on Gilenya (fingolimod) within 24 hours of starting treatment last December.

While the cause of death in this case has not been firmly established, is known that Gilenya can cause cardiovascular side effects such as a slow heart rate or palpitations. 

For that reason the drug is contraindicated in patients with history or presence of certain cardiac conditions, including heart attack or stroke in the past six months, second- and third-degree atrioventricular (AV) block and other cardiac rhythm disturbances.

The updated wording notes that all patients starting treatment with the product should have an electrocardiogram (ECG) before the first dose and six hours after, as well as hourly measurements of blood pressure and heart rate.

The same monitoring regimen should be carried out if patients restart Gilenya treatment after an interruption, according to the new labelling. Novartis said the revisions bring the FDA's investigation into the safety of the drug to a close.

Meanwhile, the EMA's Committee for Medicinal Products for Human Use (CHMP) has completed a review of 15 sudden or unexplained deaths among patients taking Gilenya.

It concluded that while a definitive link with the drug cannot be established as all the patients had pre-existing cardiovascular conditions, it would be prudent to contraindicate use of the drug in "patients with a history of cardiovascular and cerebrovascular disease or who take heart-rate lowering medication".

The CHMP also recommended ECG, heart rate and blood pressure monitoring in line with the US label changes, but concluded that with these measures in place the benefits of the drug still outweigh its risks.

Evidence of a further potential risk emerged just last week, when Novartis confirmed that a patient treated with Gilenya, developed a rare form of brain disorder that has been linked to rival drug Tysabri from Biogen Idec and Elan.

The patient who developed the disorder, known as progressive multifocal leukoencephalopathy, had previously been treated with Tysabri (natalizumab) but it is not possible to rule out Gilenya (fingolimod) was involved, according to Novartis.

As of February, approximately 36,000 patients had been treated with Gilenya in clinical trials and in the post-marketing setting, according to pharma company.

The product fulfils an important role as an alternative to injectable beta interferon therapy and is a strong growth product for Novartis, with sales last year reaching $494m and expected to top $1bn at peak.