FDA updates Gilenya label after safety review

The US Food and Drug Administration (FDA) has revised the labelling of Novartis' oral multiple sclerosis drug Gilenya to contra-indicate its use in patients with a history of heart disease or stroke, after completing a review of the drug's safety.

The review was prompted by the death of a patient in the US less than 24 hours after receiving a first dose of Gilenya (fingolimod) in December 2011. The drug is known to cause side effects such as slow heart rate or palpitations in some patients, and has also now been contraindicated in patients taking anti-arrhythmic drugs.

Novartis recently added a requirement for cardiovascular monitoring to the Gilenya's labelling - with an electrocardiogram (ECG) before the first dose and six hours after, as well as hourly measurements of blood pressure and heart rate, but the FDA's latest revisions go further. 

Specifically, the FDA now recommends that cardiovascular monitoring be extended beyond six hours in certain higher-risk patients, such as those who develop slow heart rate (bradycardia) after the first dose or who have conditions which mean that bradycardia may not be tolerated. Extended monitoring should include continuous ECG monitoring that continues overnight.

"FDA remains concerned about the cardiovascular effects of Gilenya after the first dose," said the agency in a statement, although it stressed that no causative link between the death and Gilenya could be established.

The patient was known to have extensive brainstem MS lesions, which can also lead to sudden death.

"Data show that, although the maximum heart rate lowering effect of Gilenya usually occurs within 6 hours of the first dose, the maximum effect may occur as late as 20 hours after the first dose in some patients," it added.

In Europe, the EMA has also investigated the safety of Gilenya after 15 deaths among patients taking the drug, and concluded last month that while a link to the drug could not be established it would be prudent to contraindicate the MS drug's use in patients with a history of cardiovascular and cerebrovascular disease and those who take heart-rate lowering medication.

Gilenya is the only oral drug for MS on the market, bringing in sales of $494m last year and has been tipped as a future blockbuster. 

That said, earlier peak sales estimates of upwards of $2bn a year have been scaled back a little in light of the safety concerns with the drug, particularly as alternative oral treatments for MS - notably Biogen Idec's BG-12 - are approaching the market.