The enormous rough diamond, called vorapaxar, that Merck (MRK 0.25%) picked up in the Schering-Plough merger has been cut smaller and smaller during costly late-stage development. The first big setback was a pricey phase 3 trial that measured the prevention of clinical events in patients with acute coronary syndrome. In November 2011, the company announced that the drug did not meet its original endpoint. This failure basically buried the drug's chances of being a primary blood thinner for anyone at risk of heart attack.
Less than half a year later, Merck presented data from a phase 3 trial that measured vorapaxar's ability to reduce risk of cardiovascular events as a secondary prevention in patients with a previous heart attack or stroke. This trial did reach its endpoint, but there was a significant increase in intracranial hemorrhage among patients that had previously suffered a stroke. Again, the potential patient pool for vorapaxar became smaller.
A must win
The FDA intends to kick off the year with a series of three cardiovascular and renal drugs advisory committee meetings. On Jan. 15, they'll be discussing a New Drug Application, or NDA, from Merck for vorapaxar. The FDA accepted the NDA for standard review in July. Merck is seeking its approval for the secondary prevention of cardiovascular events in patients with a history of heart attack, but no history of stroke or ischemic attack.
The advisory committee meeting on the 15th could be the final nail in vorapaxar's very expensive coffin. A recent study conducted by the McKinsey Center for Government shows the regulator is strongly aligned with the opinions of its independent advisory committees. During NDA and BLA focused meetings that include voting, the FDA approved nearly 88% of drugs endorsed by the committee. Over the period from 2001-2010, only two of 14 drugs not endorsed by an advisory committee later won approval.
Some success
So far it doesn't look like much of a competitor. Although vorapaxar employs a different method of preventing clots than Plavix, it is hardly the wonder drug that Merck hoped it would be. The TRA-2P trial enrolled thousands of patients that had previously suffered heart attack or stroke. About 11.2% of those taking vorapaxar suffered cardiovascular death, myocardial infarction, stroke, or urgent coronary revascularization, versus 12.4% in the placebo group. The decrease of 1.2% might be statistically significant, but hardly exciting when combined with the documented risk of cranial hemorrhaging.
Questionable now equals excluded
Vorapaxar isn't the only blood thinner likely to experience pressure from cheap generic clopidogrel. Pharmacy benefit manager Express Scripts (ESRX) is hammering away at higher cost drugs with incremental benefits. During the three months ended Sept. 30, the company raised its generic fill rate to 80.7% from 78% during the same period of the previous year. For 2014, the company updated its National Preferred Formulary to exclude 48 high-cost medications of questionable benefit with covered preferred alternatives. For Express Scripts, "preferred" usually means "inexpensive" generics.
The competition
The FDA approved generic versions of the Bristol-Myers Squibb blockbuster clopidogrel (Plavix) in May 2012. If vorapaxar does woo the committee, then later win approval, it will be competing for recent heart attack patients with an inexpensive option that physicians have had plenty of time to become comfortable with.
Luckily for Eli Lilly (LLY 0.54%), its blood thinner Effient is on the Express Scripts formulary. U.S. sales of the clot preventer reached $339 million in 2012. During the first nine months of 2013, overall sales of Effient rose 12% on year.
Effient is marketed specifically to patients that have undergone an artery opening procedure, but not necessarily sufferers of a previous heart attack. If approved, vorapaxar is likely to compete with this platelet inhibitor for some patients. Like vorapaxar, Effient also has a history of bleeding complications.
Also escaping the exclusion list is Brilinta from AstraZeneca (AZN 0.39%). This blood thinner is approved for the primary prevention of cardiovascular events in patients with acute coronary syndrome, not necessarily those with a history of heart attack. If approved, vorapaxar will likely compete with this platelet inhibitor, along with generic versions of Plavix.
AstraZeneca and Brilinta could take a serious turn for the worse in the near future. Both, the US Department of Justice and EU regulators are investigating the phase 3 trial, named PLATO, that pitted Brilinta against Plavix. Data from PLATO was used to show superiority over Plavix, and in turn to demand a much higher price. Drugmaker investigations are rarely worth getting excited about, but this one comes on the heels of a journal article published in the International Journal of Cardiology criticizing the reliability of trial data.
Take the shot
Pleasing the advisory committee on Jan. 15 would almost certainly cement a chance for vorapaxar to recoup some of the resources spent acquiring and developing the compound. The drug's different mechanism of action might be enough for payers and physicians to try it alongside existing treatments. Also, if the investigation of the PLATO trial turns out badly for AstraZeneca, it could play right into Merck's hand.
It's a long shot, but with both trials already paid for, it's certainly one worth taking. Let's just hope Merck doesn't initiate another vorapaxar trial if it doesn't win this time around.
