Roche diabetes pipeline shrinks to two
Roche's efforts to expand its cardiometabolic pipeline stalled Wednesday when the Swiss company announced it halted development of its experimental diabetes medication aleglitazar. The company said in a statement that an independent Data and Safety Monitoring Board recommended closing the study over “safety signals and lack of efficacy.”
The New York Times reports that these safety issues in the AleCardio study included increased risk of fractures, kidney problems and heart failure. Hints of potential kidney issues popped up in the 2012 results of the Phase II AleNephro study, which indicated that type 2 diabetes patients with moderate renal impairment experienced decreased renal function that was reversible.
The cohort for the AleCardio study comprised patients with a recent acute coronary event, but Roche said it will end all aleglitazar studies, meaning the other two in its pipeline line-up—cardiovascular risk reduction in type 2 or pre-diabetes, type two diabetes—are now wiped from the board of possible regulatory submission.
The drug's promise was threefold—its potential to reduce the risk of heart attack and stroke, as well as to keep an eye on glucose levels for type 2 diabetics. If successful, the drug could have enabled patients to knock out three major concerns with one medication. Aleglitazar attempted to do this by targeting two peroxiosome proliferator-activated receptors (PPARs), with one targeting triglycerides and another insulin sensitivity.
GlaxoSmithKline's Avandia, which belongs to a different class of PPAR agonists, focuses on insulin sensitivity. The FDA recently voted to lift restrictions put in place three years ago over Avandia's heart-risk concerns. Takeda's Actos, which acts on the same type of PPAR agonists as Avandia, has also been scrutinized for possible risks.
Roche is not the only one to fail in bringing a new PPAR agonist to market. Bristol-Myers Squibb bailed on a similar approach in 2005 after the FDA wanted additional data, while Takeda, Merck and AstraZeneca were forced to abandon similar efforts, over side effects including liver problems, tumors and kidney issues.
Roche is still studying two diabetes medications: dual agonist peptide analogue RG7697, which is similar to GLP-1 and GIP hormones, and the oral SGLT2 inhibitor tofogliflozin, in partnership with Chugai.