The US Food and Drug Administration (FDA) has asked AstraZeneca for data to help it investigate a possible link between its diabetes drug saxagliptin and heart failure.
The move has been prompted by the results of a study published in the New England Journal of Medicine (NEJM) last year which reported a 27 per cent increased rate of hospitalisation for heart failure for saxagliptin compared to placebo.
The US regulator stressed that the review was part of a wider investigation into the cardiovascular risks posed by drugs to treat type 2 diabetes, but is unwelcome news for AZ as it takes over responsibility for the drug from former partner Bristol-Myers Squibb.
The saxagliptin franchise – which includes monotherapy Onglyza and a combination with metformin called Kombiglyze – is a key part of the diabetes portfolio acquired for $4.1bn from BMS. The franchise has predicted revenues of $1bn-plus a year, although US sales may have already been impacted by the NEJM study.
Last year AZ’s share of saxagliptin revenues was $378m, up 17 per cent on 2012. However, while strong growth was maintained in the fourth quarter outside the US, sales of the DPP-4 inhibitor in the US market were flat because of “less favourable” formulary positions.
“At this time, FDA considers information from the NEJM study to be preliminary,” said the agency. Hospitalisation for heart failure was a secondary endpoint in the trial, which was called SAVOR-TIMI 53.
Saxagliptin failed to show an impact on the primary target, which was to reduce cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke when added to usual care in patients with type 2 diabetes at high risk of cardiovascular disease.
AZ and BMS were obliged to carry out SAVOR-TIMI 53 following the publication of FDA guidelines in 2008 that required all new diabetes drugs to be tested in cardiovascular outcome studies.
The requirement was introduced in the build-up to the withdrawal of GlaxoSmithKline’s Avandia (rosiglitazone) from the European market and restriction in the US on concerns of cardiovascular toxicity. The restricted licence for Avandia in the US was relaxed last year.
Reduces Targacept alliance
Meanwhile, AZ will return rights to several preclinical compounds licensed from US biopharma company Targacept, amending a collaboration that has been ongoing between the two companies since 2005.
The identity of the compounds has not been disclosed, but Targacept said AZ continues to hold an interest in other compounds, including AZD1446, a potential treatment for Alzheimer’s disease.