There was disappointment for AstraZeneca (AZ) and Bristol-Myers Squibb’s (BMS) this week when their diabetes drug Onglyza failed to show any benefit over placebo in a large-scale cardiovascular outcomes study.
The phase IV SAVOR-TIMI-53 trial involved 16,500 people with type 2 diabetes with a history of cardiovascular disease or multiple risk factors, randomising them to treatment with either Onglyza (saxagliptin) or placebo on top of standard of care.
The dipeptidyl peptidase-4 (DPP-4) inhibitor failed to show any improvement in a composite endpoint of cardiovascular death, non-fatal heart attack or nonfatal ischaemic stroke, according to data due to be presented at the European Society of Cardiology (ESC) meeting later this year.
The results of SAVOR-TIMI-53 had been widely anticipated as a positive outcome could have opened up a new treatment avenue for people with diabetes at high risk of heart disease and lent additional momentum to Onglyza’s sales trajectory.
Last year the drug made sales of a little over $700m, and analysts had suggested that an update of the labelling to include secondary prevention in diabetics could have driven sales upwards of $2bn and provide a way for BMS and AZ to differentiate their product from DPP-4 inhibitor rivals, notably Merck & Co’s market-leading Januvia (sitagliptin) and Novartis’ Galvus (vildagliptin).
The trial was set up in the wake of new US FDA guidelines in 2009 which required pharma companies to perform cardiovascular outcome studies on new diabetes drugs.
Those guidelines were 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.
Onglyza was the first new diabetes drug to be approved by the FDA after the guidance was issued, and AZ and BMS decided to not only try to demonstrate safety with Onglyza with SAVOR-TIMI-53 but also examine a possible protective effect of the drug.
The finding on safety in such a large-scale study is likely to be a benefit to the brand regardless, given that regulators in Europe and the US recently opened investigations into the safety of DPP-4 inhibitors and other so-called incretin mimetics such as glucagon-like peptide 1 (GLP-1) agonists. Those probes are however focusing on links to pancreatitis and cancer.