Merck (MRK) is pursuing approval for the antiplatelet agent vorapaxar in patients with prior MI. Mechanistically, vorapaxar inhibits thrombotic events by antagonizing thrombin-mediated activation of platelets via the protease-activated receptor 1. This arises from a subgroup analysis of the TRA 2°P-TIMI 50 trial testing the drug in patients with prior history of MI or stroke. The initial conclusion form the trial was that Voraxapar did significantly reduce MI, stroke and death, but increased incidence of intracranial hemorrhage (ICH) in the Voraxapar treated group likely outweighs benefit. But, patients with a prior MI, with no history of stroke or transient ischemic attack (TIA), had a reduction in MI, stroke and death not associated with increased incidence of intracranial hemorrhage . The analysis was published in The Lancet with the interpretation "For patients with a history of myocardial infarction, inhibition of protease-activated receptor 1 with vorapaxar reduces the risk of cardiovascular death or ischemic events when added to standard antiplatelet treatment, including aspirin, and increases the risk of moderate or severe bleeding". The moderate and severe bleeding did not include increased risk of ICH, in which there was a statistically non-significant increase. Based on this data, Merck, in 2013, plans to file plans to file applications for this indication in the US and Europe. As this moves forward with regard to forcasting approval (or disapproval), safety will likely be the key issue on regulators' minds with a drug that is associated with the risk of ICH.
Another key issue will be potential market size and revenue. Plavix (clopidogrel) revenue was US$4.1 billion in 2011, but the FDA approved generic version of clopidogrel in May of 2012. Plavix is marketed by Bristol-Myers Squibb (BMY) and Sanofi (SNY). But one key issue that should be considered and already pointed out by Forbes, this study is the first to show a benefit for more than a year with the use of antiplatelet drugs, which could, in theory, increase revenue dramatically. From the Forbes article, lead author Dr Benjamin Scirica commented, "To our knowledge, our study is the first to show a benefit of adding intense antiplatelet treatment to aspirin for long-term secondary prevention of thrombotic events in patients who have had a heart attack."
The market for vorapaxar is potentially large, in the billions of dollars clearly, if it is approved. Merck also plans, according to Reuters, to seek approval for two cardiovascular drugs in 2013 and trials of Anacetrapib, which raises HDL cholesterol (the good cholesterol). Lily (LLY) is developing the second drug in this class, Evacetrapib. Take note, dalcetrapib, also in this class, has had development terminated by Roche Holding (RHHBY). Anacetrapib has a greater impact on HDL cholesterol levels, however. [See Seeking Alpha for a discussion of CETP inhibitors]. Merck is currently seeking approval of a combination drug, ezetimibe and atorvastatin, for treating hyperlipidemia which will also be included in an upcoming review of Merck's pipeline which has included the potential block buster sleep drug suvorexant. According to Yahoo Finance, Merck's current PE is about 21, although not small, it continues to make analyzing Merck's pipeline worthwhile for investors. In the end, buying Merck shares should require analysis of loss of revenue from drugs coming off patent and the potential for new drugs being approved and revenue from these drugs. Vorapaxar may potentially have multibillion dollar revenue for Merck and should be part of this continuing analysis of Merck's pipeline.
Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.