Federal health officials say a Johnson & Johnson drug helps prevent deadly blood clots in patients getting hip or knee replacement, but it also carries a risk of serious internal bleeding.
Johnson & Johnson and partner Bayer have asked the Food and Drug Administration to approve their once-daily pill, rivaroxaban, as an anticlotting drug to stop blood clots in legs and those that can travel to the lungs. More than 800,000 U.S. patients receive hip or knee replacements each year, and an estimated 40 to 60 percent are at risk of blood clots.
But FDA regulators said in documents posted online Tuesday that the drug carries nearly twice the risk of bleeding of Sanofi-Aventis' Lovenox, the top-selling blood thinner used by patients receiving orthopedic implants.
On Thursday the agency will ask a panel of cardiology experts to weigh in on the drug's risks and benefits. The FDA is not required to follow the advice of its panel, though it usually does.
After reviewing four studies with more than 12,000 patients, the FDA said major bleeding occurred in 0.4 percent of patients on the J&J drug, compared with 0.2 percent of those taking Sanofi's drug, known chemically as enoxaparin. The drug was Paris-based Sanofi's biggest product last year, with sales of $3.5 billion.
"The evidence that administration of rivaroxaban could lead to bleeding events in significantly more patients relative to enoxaparin amplifies this safety concern," states the FDA's review, posted online Tuesday.
Other potential risks
Regulators also voiced concerns about potential risks of liver injury or toxicity, a common side effect with blood-thinning drugs. Bayer and J&J have proposed that the drug would be used for only two weeks by knee surgery patients and five weeks by hip surgery patients.
But the FDA is concerned doctors could use it for longer periods. The agency will ask its panelists whether there is enough information to gauge the risks of the drug over the long term.
The agency said it asked the companies to develop a lower-dose version of rivaroxaban that could be used by patients with liver or kidney problems. According to the agency, the companies "regarded this modification as unnecessary."
But a J&J spokesman said the company "is actively working with the FDA on this issue to assure the best balance of benefit and risk."
The FDA also said the companies declined to design a risk minimization strategy for their drug, or a plan to help doctors and patients use the drug safely. But the company said it has submitted a number of plans to reduce the drug's risks, including education and outreach programs.
The agency will have to weigh rivaroxaban's risks against its promise as a lifesaving medication.
Designed to be safer
In four studies of knee and hip replacement patients, rivaroxaban cut the risk of blood clots or death in half, to 0.6 percent, compared with 1.3 percent for patients taking Lovenox.
Rivaroxaban is one of several new anticlotting drugs designed to be safer and more effective than older treatments. One mainstay of anticlotting treatment, Coumadin or warfarin, requires patients to undergo frequent blood tests because a too-high or too-low dose can lead to strokes or dangerous bleeding.
"If we look at our program, we believe we have a very effective drug with a very positive benefit risk profile," J&J Vice President Peter Wildgoose said in an interview last week.
J&J is studying the drug in more than 60,000 patients for additional uses, including stroke prevention and treatment of coronary artery disease.
If the drug is approved, Johnson & Johnson's Ortho-McNeil business will sell the drug in U.S., while Bayer HealthCare AG will have marketing rights in other countries.