Bristol-Myers Squibb Company and AstraZeneca announced that the US Food and Drug Administration's (FDA) Endocrinologic and Metabolic Drugs Advisory Committee determined (by a vote of 10 to 2) that the data supporting the new drug application for Onglyza (saxagliptin) for the treatment of adults with type-2 diabetes were sufficient to rule out unacceptable cardiovascular risk relative to comparators in the programme.
The committee unanimously recommended that the sponsors perform a post-marketing trial to confirm the cardiovascular profile of Onglyza. Bristol-Myers Squibb and AstraZeneca are working on a series of phase-IIIb and IV studies, including a large, controlled, randomized, post-marketing trial, to further characterize the long-term clinical effectiveness as well as the cardiovascular profile of Onglyza. The companies will now work with the FDA to finalize the post-marketing trial design.
"Bristol-Myers Squibb and AstraZeneca are encouraged by the Committee's recommendation. We will work closely with the FDA to support the review of Onglyza," said Brian Daniels, senior vice president, Global Development and Medical Affairs, Bristol-Myers Squibb.
Onglyza is an investigational, selective, reversible inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme. The Onglyza application to the FDA includes use as a monotherapy, as an adjunct to diet and exercise, use in combination with three types of commonly used oral anti-diabetic (OAD) medications - metformin, thiazolidinediones and sulfonylureas (SUs) when the single agent alone does not provide adequate glycemic control, as an adjunct to diet and exercise - and use in initial combination therapy with metformin, as an adjunct to diet and exercise.
The FDA Endocrinologic and Metabolic Drugs Advisory Committee based its recommendation on review of data from the comprehensive Onglyza clinical development program, which included more than 5,000 individuals, more than 4,000 of whom were given Onglyza. Data presented included safety and efficacy results from six pivotal phase-III trials, in addition to comprehensive post hoc pooled analyses evaluating cardiovascular risk in the phase-IIb and phase-III studies, which included individuals followed for up to 2.5 years and more than 3,700 person-years of exposure to Onglyza. The post hoc pooled analyses did not show evidence of a cardiovascular safety signal in individuals taking Onglyza.
The FDA is not bound by the Advisory Committee's recommendations, but takes its advice into consideration when reviewing new drug applications. Bristol-Myers Squibb and AstraZeneca will review the information leading to the Committee's decision and continue to work closely with the FDA to support the review of Onglyza. The new drug application for Onglyza was submitted to the FDA on June 30, 2008, and has an action date of April 30, 2009.
Onglyza, an investigational drug under joint development by Bristol-Myers Squibb and AstraZeneca for the treatment of type-2 diabetes, was specifically designed to be a selective inhibitor with extended binding to the DPP-4 enzyme, with dual routes of clearance. Onglyza is being studied in ongoing and further planned clinical trials.
DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins.