Merck’s Simvastatin/Niacin Combination Delayed By Formulation Issues
This article was originally published in The Pink Sheet Daily
Executive Summary
Regulatory submission of the investigational HDL-raising, LDL-lowering fixed-dose combination, MK-0524B, had been planned for 2007.
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Merck will not file its fixed-dose combination drug, MK-0524B, combining MK-0524A (extended-release niacin and a niacin flushing inhibitor) and Zocor (simvastatin), in 2007 as originally anticipated due to formulation problems, the company announced Sept. 29. The drug maker will continue running its late-stage clinical program to support the regulatory filing, but did not announce a new timeline for submitting an NDA for the triple combination. In comments to "The Pink Sheet" DAILY, Merck said it remains committed to the clinical development program for the fixed-dose combination formulation. The delay marks the second time Merck has announced formulation issues with the drug, but the first to impact the regulatory filing timeline. In March, Merck announced it was having problems formulating the drug, but said it would continue with a Phase III clinical trial by co-administering the separate components (1 (Also see "Merck’s HDL-Raising Cholesterol Combo Has “Formulation Issues”" - Pink Sheet, 8 Mar, 2006.)). The firm's plans to bridge that data from the co-administration to the MK-0524B fixed-dose combination "remain unchanged." Merck is independently developing MK-0524A, the fixed-dose combination of extended-release niacin and a DP-1 selective inhibitor to combat the flushing side effect of the drug. The firm said it remains on track to file that combination in 2007. Oxford University is also moving ahead with preparations for patient enrollment in a 20,000-patient study, HPS2-THRIVE, studying MK-0524A plus simvastatin, Merck added. That $79.2 mil. trial, Treatment of HDL to Reduce the Incidence of Vascular Events, was announced in May (2 (Also see "Merck’s Niacin Combination Drug To Be Evaluated In Heart Protection Study 2" - Pink Sheet, 30 May, 2006.)). Merck is developing MK-0524A for the treatment of atherosclerosis with the aim of raising HDL-cholesterol and lowering LDL. MK-0524B would have the added cardiovascular benefit of simvastatin, while providing Merck with a means to supplant its cholesterol franchise after Zocor went generic in June. The company announced it was moving the two novel cholesterol therapies into Phase III, highlighting them as core pipeline projects during its annual business meeting in December (3 (Also see "Merck Unveils HDL-Cholesterol Drug Candidates" - Pink Sheet, 15 Dec, 2005.)). Merck recently ended development of a Phase II G protein-coupled receptor which also could have boosted its cardiovascular franchise (4 (Also see "Merck Ends Development Of Phase II Artherosclerosis Candidate" - Pink Sheet, 26 Sep, 2006.)) The delay in filing could give Pfizer a competitive edge with its own HDL-raising therapy, depending upon the outcome of its data. The company is developing a fixed-dose HDL-raising/LDL-lowering cholesterol combination with torcetrapib and Lipitor (atorvastatin). That combination could be filed as early as 2007. Pfizer expects to have data on the combination's impact on LDL and HDL levels, and imaging data on remodelling of the cardiovasculature by the end of 2006. But data from ongoing cardiovascular morbidity and mortality studies will not be available until 2008, and it is unclear what will be needed to secure FDA approval for HDL elevation. The combination has also been associated with a slight increase in blood pressure. -Jessica Merrill ([email protected]) |