A Long Road Ahead for This Embattled Blood Thinner

The enormous rough diamond that Merck picked up in the Schering-Plough merger has been cut smaller and smaller during costly late stage development. Soon, investors will know if it has a chance of recouping its costs.

Jan 6, 2014 at 4:48PM

The enormous rough diamond, called vorapaxar, that Merck (NYSE:MRK) 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 (NASDAQ: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 (NYSE:LLY), 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 (NYSE:AZN). 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.

The Fool's top stock for 2014
There's a huge difference between a good stock, and a stock that can make you rich. The Motley Fool's chief investment officer has selected his No. 1 stock for 2014, and it's one of those stocks that could make you rich. You can find out which stock it is in the special free report: "The Motley Fool's Top Stock for 2014." Just click here to access the report and find out the name of this under-the-radar company.

Cory Renauer has no position in any stocks mentioned. The Motley Fool recommends Express Scripts. The Motley Fool owns shares of Express Scripts. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.

1 Key Step to Get Rich

Our mission at The Motley Fool is to help the world invest better. Whether that’s helping people overcome their fear of stocks all the way to offering clear and successful guidance on complicated-sounding options trades, we can help.

Feb 1, 2016 at 4:54PM

To be perfectly clear, this is not a get-rich action that my Foolish colleagues and I came up with. But we wouldn't argue with the approach.

A 2015 Business Insider article titled, "11 websites to bookmark if you want to get rich" rated The Motley Fool as the #1 place online to get smarter about investing.

"The Motley Fool aims to build a strong investment community, which it does by providing a variety of resources: the website, books, a newspaper column, a radio [show], and [newsletters]," wrote (the clearly insightful and talented) money reporter Kathleen Elkins. "This site has something for every type of investor, from basic lessons for beginners to investing commentary on mutual funds, stock sectors, and value for the more advanced."

Our mission at The Motley Fool is to help the world invest better, so it's nice to receive that kind of recognition. It lets us know we're doing our job.

Whether that's helping the entirely uninitiated overcome their fear of stocks all the way to offering clear and successful guidance on complicated-sounding options trades, we want to provide our readers with a boost to the next step on their journey to financial independence.

Articles and beyond

As Business Insider wrote, there are a number of resources available from the Fool for investors of all levels and styles.

In addition to the dozens of free articles we publish every day on our website, I want to highlight two must-see spots in your tour of fool.com.

For the beginning investor

Investing can seem like a Big Deal to those who have yet to buy their first stock. Many investment professionals try to infuse the conversation with jargon in order to deter individual investors from tackling it on their own (and to justify their often sky-high fees).

But the individual investor can beat the market. The real secret to investing is that it doesn't take tons of money, endless hours, or super-secret formulas that only experts possess.

That's why we created a best-selling guide that walks investors-to-be through everything they need to know to get started. And because we're so dedicated to our mission, we've made that available for free.

If you're just starting out (or want to help out someone who is), go to www.fool.com/beginners, drop in your email address, and you'll be able to instantly access the quick-read guide ... for free.

For the listener

Whether it's on the stationary exercise bike or during my daily commute, I spend a lot of time going nowhere. But I've found a way to make that time benefit me.

The Motley Fool offers five podcasts that I refer to as "binge-worthy financial information."

Motley Fool Money features a team of our analysts discussing the week's top business and investing stories, interviews, and an inside look at the stocks on our radar. It's also featured on several dozen radio stations across the country.

The hosts of Motley Fool Answers challenge the conventional wisdom on life's biggest financial issues to reveal what you really need to know to make smart money moves.

David Gardner, co-founder of The Motley Fool, is among the most respected and trusted sources on investing. And he's the host of Rule Breaker Investing, in which he shares his insights into today's most innovative and disruptive companies ... and how to profit from them.

Market Foolery is our daily look at stocks in the news, as well as the top business and investing stories.

And Industry Focus offers a deeper dive into a specific industry and the stories making headlines. Healthcare, technology, energy, consumer goods, and other industries take turns in the spotlight.

They're all informative, entertaining, and eminently listenable ... and I don't say that simply because the hosts all sit within a Nerf-gun shot of my desk. Rule Breaker Investing and Answers contain timeless advice, so you might want to go back to the beginning with those. The other three take their cues from the market, so you'll want to listen to the most recent first. All are available at www.fool.com/podcasts.

But wait, there's more

The book and the podcasts – both free ... both awesome – also come with an ongoing benefit. If you download the book, or if you enter your email address in the magical box at the podcasts page, you'll get ongoing market coverage sent straight to your inbox.

Investor Insights is valuable and enjoyable coverage of everything from macroeconomic events to investing strategies to our analyst's travels around the world to find the next big thing. Also free.

Get the book. Listen to a podcast. Sign up for Investor Insights. I'm not saying that any of those things will make you rich ... but Business Insider seems to think so.

Compare Brokers