Roche scraps diabetes drug as pRED racks up another PhIII fiasco

Once again, Roche's pRED group has a big Phase III snafu to answer for. The Basel-based R&D side of the pharma giant ($RHHBY)--distinct from the gRED operations at Genentech--has pulled the plug on the diabetes drug aleglitazar, once tapped as a blockbuster hopeful.

The company reports that investigators detected "safety signals and lack of efficacy" during the late-stage AleCardio study, which involved thousands of patients. A spokesperson tells FierceBiotech that patients experienced side effects that involved their kidneys and hearts.

"Whilst phase II data supported the investigation of the potential benefit of aleglitazar in reducing cardiovascular events in type II diabetes, 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," noted the spokesperson in an email.

"Roche is working with investigators to support the management of patients and their transition from aleglitazar treatment to other blood sugar control therapies," said Hal Barron, head of global product development at Roche. The drug turns on protein receptors known as PPARs. In Phase II, a small group responded well to the drug.  

Analysts weren't surprised by the failure, though. AstraZeneca ($AZN) and Bristol-Myers Squibb ($BMY) had their own late-stage setbacks in the same field 7 years ago, leading many observers to wonder why Roche continued to pursue its work on the drug. Four years ago, Dr. Bernard Charbonnel, of the University of Nantes in France, noted in a piece on PPARs that more than 50 such drugs had failed clinical trials due to safety concerns. The defeat of muraglitazar and tesaglitazar in Phase III was the crowning setback for many experts, casting a permanent pall on the whole field.

Long after safety questions were raised, though, Roche was still highlighting aleglitazar as a solid blockbuster hopeful in the late-stage pipeline. Now Roche can add another high-profile failure after setting up a study with 7,000 patients, despite the odds that they were exposing patients to serious side effects.

John Reed

Roche's pRED also pursued work on dalcetrapib after Pfizer's ($PFE) rival therapy had succumbed to safety issues. After Roche announced it was scuttling dalcetrapib the company set out to reorganize pRED, shutting down its sprawling complex in Nutley, NJ--though a translational R&D group of about 200 will move to new facilities Manhattan at the end of the year. An outsider, John Reed, was also brought in from Sanford-Burnham several months ago to take charge. Since then the pRED group has been reevaluating its research strategy as it tries to come up with a workable formula while its West Coast group under Genentech continues to come up with top new cancer drugs.

Some analysts think they might want to try some new research fields.

"The fact is, Roche isn't particularly good in metabolic and cardiovascular drugs and should exit its research in these areas," Zuercher Kantonalbank analyst Michael Nawrath told Reuters.

Andrew Pollack at The New York Times notes that the Roche failure could also influence the FDA's review of GlaxoSmithKline's Avandia. While aleglitazar activated both PPAR alpha and gamma, Avandia targeted primarily the gamma receptor. Questions about its safety spurred European regulators to red-flag the drug while the FDA severely restricted its use. But an advisory panel recently called on the agency to loosen its restrictions. Now the FDA will likely consider whether the risks Roche saw in Phase III  could reflect problems for Avandia, or whether they might ease regulators' concerns. 

- here's the press release
- read the Reuters story
- get the story from The New York Times

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