Citing "safety signals and lack of efficacy," Roche has announced that it is terminating clinical trials of aleglitazar, a dual PPAR agonist that the company had been pursuing as a treatment for type 2 diabetes that lowered cardiovascular risk in addition to controlling glucose.
In a statement on July 10, the company said that the decision was based on a recommendation of the independent Data and Safety Monitoring Board (DSMB) to halt the AleCardio study, a phase III study of aleglitazar in patients with type 2 diabetes and a recent acute coronary syndrome event. The company also has decided to terminate all other studies of the drug.
"While phase II data supported the investigation of the potential benefit of aleglitazar in reducing cardiovascular events in type II diabetes, a lack of efficacy and an increased rate of adverse events including fractures, renal impairment and heart failure were seen in the AleCardio trial, resulting in an unfavorable benefit/risk profile," a company spokesperson said.
"We are disappointed by this outcome as we hoped that aleglitazar would provide significant benefit for patients with type 2 diabetes who are at risk of cardiovascular disease," Dr. Hal Barron, Roche’s chief medical officer and head of global product development, said in the statement. The company "is working with investigators to support the management of patients and their transition from aleglitazar treatment to other blood sugar control therapies," he added.
When the company announced the launch of phase III trials of aleglitazar in June 2009, the drug was described in a Roche statement as "uniquely designed to reduce cardiovascular morbidity and mortality" in high-risk patients with type 2 diabetes. The statement said that the results of SYNCHRONY, a phase II, placebo-controlled dose-ranging study, showed that aleglitazar "had a balanced synergistic effect on both lipid and glucose control with a good safety and tolerability profile" in type 2 diabetes patients.
Roche plans to analyze the data from the AleCardio study and will present the results at a medical meeting, according to the statement announcing the end of the study.
Aleglitazar is a peroxisome proliferator–activated receptor (PPAR) co-agonist, activating both PPAR-alpha and PPAR-gamma. As of July 10, nine studies of aleglitazar were listed as either recruiting or as active and not recruiting on clinicaltrials.gov.
The results of the SYNCHRONY study were published in 2009 (Lancet 2009;374:126-35).