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Safety Risks, Generic Threat Scale Down Big Hopes
Lilly's new blood thinner, prasugrel, got top billing at the American Heart Association's (AHA) annual bash in Orlando, FL, last weekend, but its performance had few pulses racing.
When the drugmaker unveiled much-anticipated results from its giant, gutsy Phase III Triton study pitting its clot-buster against the $6 billion market leader, Plavix, the verdict was decidedly mixed. As expected, the experimental ADP receptor inhibitor, which Lilly codevelops with Daiichi Sankyo, was 19 percent more effective than its older sibling, marketed by BMS and Sanofi-Aventis, in stopping cardiovascular death, nonfatal heart attacks, and strokes. Yet prasugrel also proved riskier than Plavix, causing 32 percent (a total of 35) more cases of serious bleeding, the blood-thinner market's Achilles' heel.
"It was no surprise that prasugrel was found to be more potent and more consistent across different patients groups than Plavix," Wood Mackenzie life sciences Principal Analyst Martyn Link said. "The safety news was what we were all waiting for. While the increased risk was relatively small, the data raise enough concern that, taken with other challenges, we have to reevaluate prasugrel's prospects." He added that his firm had cut the drug's estimated sales for 2013 in half, to $770 million.
Most other analysts were quick to downgrade prasugrel's fortunes, despite—or because of—the fact that the Triton data are extremely complex. While prasugrel beat Plavix on every benefit measure, teasing out the variables (such as low weight and previous cardiac events) for an acceptable level of risk is a far more formidable task. "Assessing whether a patient is a good candidate for the drug or not is going to be a complicated message for doctors to buy into, especially when they're already comfortable with Plavix's safety profile," Link said.
Not surprisingly, Lilly offered a much sunnier take. "The large majority of patients in the Triton trial—some 80 percent—demonstrated a significant improvement in net clinical benefit," John Alexander, MD, global head of R&D at Daiichi Sankyo. "For the 20 percent at risk of increased bleeding, the net clinical benefit of prasugrel was comparable to [Plavix]."Numerous cardio specialists also lined up at the AHA meeting to praise the new treatment option, including frequent industry gadfly Steven Nissen, MD, chairman of cardiology at the Cleveland Clinic. "The drug ought to be approved with careful warnings," Nissen told Bloomberg News. "I would prefer this drug if I were a patient. I wouldn't use it in frail, elderly patients where the benefits aren't nearly as clear."
The drugmakers are full steam ahead with plans to submit prasugrel for FDA approval by year's end. But they're also hedging their bets, having just announced the launch of a late-stage trial pitting prasugrel against Plavix in a new group of patients—those with acute coronary syndrome, including angina and heart attacks. These folks typically end up in emergency rooms, and would presumably look more kindly on prasugrel's higher efficacy, higher-risk profile than many other patients, especially in short-term doses.The 10,000-person trial will be up and running by mid-2008. Whether FDA will wait for these results before giving prasugrel the nod remains to be seen. But regardless, with generic versions of Plavix ready to flood the market in 2011, Lilly and Daiichi Sanyko have an ever-narrowing window in which to perfect a winning risk/benefit message.