Roche has terminated its development of aleglitazar, a dual peroxisome proliferator-activated receptor-α (PPARα) and PPARγ agonist for type 2 diabetes.

The lowdown: Roche pulled the plug on its programme for aleglitazar owing to the lack of efficacy and toxicity signals flagged by an independent data and safety monitoring board in a Phase III trial known as AleCardio.

This may be the final nail in the coffin for modulators of PPARs, as aleglitazar was the last remaining agent in late-stage trials. This follows major failures and programme terminations from numerous other companies, as well as the long-running controversy over the cardiovascular risks of the PPARγ agonist rosiglitazone (Avandia; GlaxoSmithKline).

Roche pushed ahead with aleglitazar in the hope that its receptor-binding profile might sidestep the cardiovascular risks seen with other dual PPARα and PPARγ agonists (Nature Rev. Drug Discov. 9, 668–669; 2010). Eyes now turn to the small number of remaining candidates in Phase II trials, which include Genfit's GFT505, a dual PPARα and PPARδ agonist for non-alcoholic steatohepatitis, and InteKrin's INT-131, a partial PPARγ agonist for type 2 diabetes.