The odds of Merck & Co. getting its two niacin combination drugs on the market in the next five years aren't looking good. That's because FDA wants to see cardiovascular outcomes data on the investigational cholesterol meds, MK-0524A (niacin/laropiprant), previously known as Cordaptive , and the follow on, MK-0524B (niacin/laropiprant/ simvastatin).

Although Merck already has a 20,000-patient outcomes trial ongoing, HPS2-THRIVE, the study won't be completed until January 2013. The timeline pushes back the likely refiling for MK-0524A until at least 2013, which - unfortunately for Merck - comes after Cozaar / Hyzaar and Singulair start to lose patent protection.

Patents covering Cozaar/Hyzaar expire in 2010, and patent protection for Singulair expires in 2012.

The company updated investors on the regulatory status of MK-0524A and MK-0524B June 20 following a meeting with FDA in which the agency expressed concerns over safety and efficacy.

Word of the delay comes as little surprise, though, since MK-0524A was deemed "not approvable" by the agency on April 28, with the agency also nixing the name Cordapitve (¹ Also see "Merck: Second “Not Approvable” Letter In Two Days – This Time, Cordaptive" - Pink Sheet, 28 April, 2008.).

Plus, FDA recently has been pushing for more outcomes data, following the Vytorin debacle - another combination drug for which Merck is a partner.

Still, Merck said it is holding out hope for an earlier MK-0524A filing, if the firm is able to provide the agency with data addressing the issues raised by FDA ahead of the completion of HPS2-THRIVE.

"In that event, the earliest Merck would file a complete response to the FDA action letter would be 2010," the company said, adding that it will not seek approval for MK-0524B in the U.S. until it files a "complete response" for MK-0524A.

The firm had previously indicated it would file MK-0524B later this year.

Despite the news, Merck remains confident it can meet its double-digit compound annual earnings per share growth goal from 2005 through 2010. Sales of Cozaar/Hyzaar and Singulair in the U.S., however, account for roughly $4.2 billion in sales (based on 2007 figures), and the loss of those drugs will be a significant hit to the top line after 2010.

A few months ago, Cordaptive seemed like a fairly straightforward new-drug combination, with a fair shot at FDA approval. Extended-release niacin has been on the market for years in the form of Abbott's Niaspan , and the addition of laropiprant - a selective prostaglandin D2 receptor-1 antagonist - is intended to limit the flushing side effect associated with niacin.

Merck is not saying exactly what FDA's specific issues are with the drug, but since laropiprant is the new agent in the combination, the agency's concerns likely lie there. One factor hurting Merck's case for approval is that laropiprant addresses an annoying side effect associated with niacin, but not a life-threatening one.

Despite doubts on the part of FDA, the combination was given a positive opinion from the EU Committee on Medicinal Products for Human Use in April, and Merck said it will continue to pursue approval for both drugs in other countries around the world.

-Jessica Merrill (j.merrill@elsevier.com)

FDA Seeks Outcomes Data For Merck’s MK-0524A

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