Monday, December 03, 2007

Prasugrel: Lilly Tries to Stop the Bleeding (Part 2)

The speculation about the prospects for Lilly’s clot prevention drug prasugrel continues.

The latest turn has been a rebound for Lilly, prompted at least in part by a November 28 note by Credit Suisse analyst Catherine Arnold. The note reports some interesting survey data on projected use of prasugrel by cardiologists. What Arnold heard in the responses is further support for her view that the drug will indeed be a significant new product for Lilly, with peak sales in the range of $2.5 billion.

Lilly shares have been on a rollercoaster ride for six weeks now surrounding release of the pivotal trial data for prasugrel. Unfortunately for Lilly, most of the ride has been downhill. (We wrote about Lilly CEO Sidney Taurel’s response to the media and investor frenzy surrounding prasugrel last week.)

For now, many analysts remain concerned about an increased risk of major bleeding associated with the drug. In today’s world, they fret that even a demonstration of superior efficacy vesus the market leader, Bristol-Myers Squibb/Sanofi Aventis’ clopidogrel (Plavix), isn’t enough to overcome any hint of a safety risk.

The pivotal trial data undeniably limit the market for prasugrel (approximately 20% of the patients enrolled in the trial were in one of three subgroups Lilly says shouldn’t get the drug). Some analysts expect that the impact will be greater than that, with doctors choosing the more conservative approach of using Plavix first as much as possible. And the biggest fear of all is that FDA simply won’t approve the drug.

Arnold, clearly, is in the more bullish camp. In her view, investors have over-reacted to the safety issue. Even with limitations on the patient population, prasugrel only needs to capture about a 25% share of the current market for Plavix to generate $2.5 billion in peak revenues.

That type of market share is very achievable, Arnold says. The survey suggests that cardiologists will use prasugrel in more than a third of their PCI patients.

“Surprisingly, the respondents were also very likely to use prasugrel in patients with coronary artery disease who are being medically managed (patients with unstable angina or a recent MI who do not undergo PCI) and patients with established peripheral arterial disease,” Arnold reports. “These are large segments of the antiplatelet market where there is no data to support the use of prasugrel currently but, based on these results and other research we have conducted, we think prasugrel will generate modest off-label use.”

That sure sounds like good news for Lilly. But is it?

The willingness of cardiologists to shrug off the safety questions about prasugrel may be perfectly justified medically, and it would certainly be a great boost for the drug commercially. But it is also exactly the reason why FDA has been so tough on NDAs—and why Congress has given the agency new drug safety tools to control the use of new drugs after approval.

To us, the path for approval of prasugrel seems clear. First, Lilly needs to convince FDA that the subpopulations it has identified where the drug should and should not be used are indeed supported by the data. Lilly says the risk/benefit profile is not supported for the drug in patients over 75 years of age, patients who weigh less than 60 kg, and patients with a prior history of stroke or transient ischemic attack. If those patients are excluded from treatment, the relatively benefits of prasugrel look even better compared to Plavix.

Second, and most important, Lilly will need to convince FDA that the drug will in fact only be used by the subpopulations for which it is appropriate. In that case, the perception that cardiologists are eager to use the drug more broadly actually hurts—rather than considering the risk benefit profile if only the right patients use it, FDA has to consider the risk benefit profile if the wrong patients use it.

FDA’s decision on prasugrel will almost certainly come down to Lilly’s ability to present a credible risk management plan that will give FDA the confidence to say yes to the drug. In that context, the survey data showing a readiness for cardiologists to use prasugrel off-label is an obstacle, not an opportunity.

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