BMS, AstraZeneca’s Onglyza Enters Murky Regulatory Waters
This article was originally published in The Pink Sheet Daily
Executive Summary
Scrutiny of potential cardiovascular risks looms over new diabetes drugs.
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After a newly disclosed NDA filing, Onglyza is poised to become the second or third DPP-4 inhibitor on the U.S. market, but it comes under review at a time of potentially great regulatory change for diabetes drugs. Bristol-Myers Squibb and Astra Zeneca announced July 23 that it submitted type 2 diabetes drug Onglyza (saxagliptin) in the U.S. and Europe. The firms tendered the U.S. application June 30. They made the first European filing July 1. Onglyza could become the second or third DPP-4 inhibitor on the U.S. diabetes market. Merck's popular Januvia (sitagliptin), approved in 2006, was the first. Takeda submitted alogliptin (SYR-322) at the close of December (1 (Also see "Takeda Files DPP-4 Inhibitor NDA, Poised To Best Bristol/AstraZeneca, Novartis In Race For Second To Market" - Pink Sheet, 4 Jan, 2008.)). Novartis is expected to resubmit its DPP-4 candidate Galvus (vildagliptin) in mid-2009. More cardiovascular data may be needed Onglyza is embarking on the road to approval just after a key meeting of the Endocrinologic and Metabolic Drugs Advisory Committee. Early this month, committee members concluded FDA's approval standards are inadequate to assess the cardiovascular effects of type 2 diabetes therapies and voted to tighten cardiovascular review for all medications (2 (Also see "FDA Should Require Cardiovascular Outcomes Trials For All Type 2 Diabetes Drugs, Panel Says" - Pink Sheet, 2 Jul, 2008.)). Companies may be focusing too much on measuring compounds' ability to reduce blood glucose without sufficiently testing cardiovascular risk, the panel found. BMS declined to speculate about whether its application will suffice in light of the committee's recommendations, arguing that nothing has been finalized and the actual outcome of the vote is still very unclear. However, the firm did note that Onglyza has been tested extensively, with several core Phase III trials supporting the application. Onglyza performed well as a monotherapy for reducing blood glucose in a 24-week Phase III trial reported at the American Diabetes Association meeting in June (3 (Also see "Bristol-Myers Squibb Targets Mid-year Filing For Saxagliptin" - Pink Sheet, 6 Jun, 2008.)). Its adverse event profile was similar to placebo, with side effects including upper respiratory tract infection, nasopharyngitis and sinusitis. There were no confirmed cases of hypoglycemia and the drug was not linked to weight gain. At last year's ADA meeting, results from a Phase III study of over 700 patients showed Onglyza's effectiveness in combination with metformin in reducing blood glucose. The most common adverse events reported in that trial were nasopharyngitis, headache, diarrhea, upper respiratory tract infection, influenza and urinary tract infection. Researchers reported one confirmed case of hypoglycemia in each of four treatment arms (placebo and three doses of Onglyza). Convenience draws doctors to DPP-4s In an annual JP Morgan survey of 100 primary doctors and endocrinologists, 56 percent of respondents had a moderate or strong preference for GLP-1 analogs, such as Amylin's Byetta (exenatide), while only 19 percent showed a moderate or strong preference for DPP-4 inhibitors (4 (Also see "Amylin’s New Byetta Branding Plays Up Weight Loss" - Pink Sheet, 22 Jul, 2008.)). But ease of use with oral administration and lack of acute toxicity are drawing doctors to the DPP-4s in greater numbers, according to the survey, published July 17. Utilization of Januvia was much higher in this year's survey, with 17 percent using the drug, up by more than 50 percent from the 11 percent figure reported in 2007. In comparison, Byetta utilization rate was flat at 11 percent, analysts reported. Preferences have become manifest in sales figures. Januvia earned Merck $668 million in 2007 and $272 million in the first quarter of 2008, up 300 percent from the same period last year (5 (Also see "Merck Revises Guidance To Include $700 Million Less In Vytorin/Zetia Sales" - Pink Sheet, 21 Apr, 2008.)). An 18-week, head-to-head trial comparing Onglyza to Januvia, both as an add-on therapy to metformin, is under way, with results expected in 2009. Separately, data from new Phase III studies on Onglyza are due to be presented at the European Association for the Study of Diabetes meeting in Rome in September. -Emily Hayes ([email protected]) |