A negative review from Food and Drug Administration staff bodes ill for a new blood thinner from Johnson & Johnson.
An FDA staff report released Tuesday recommends against approving Xarelto for preventing strokes in patients with a common irregular heart rhythm called atrial fibrillation. It says an additional study is needed.
The report states that data from a late-stage study of more than 14,000 patients, known by the acronym ROCKET, doesn't make clear how safe Xarelto is, or whether it's as effective as widely used warfarin.
Johnson & Johnson and partner Bayer Healthcare of Germany developed the drug, known chemically as rivaroxaban.
"ROCKET does not show convincingly that rivaroxaban is as effective as warfarin when the latter is used skillfully," states the 388-page report by three FDA staff reviewers.
The report adds that there are several reasons to deny the makers' request to include a claim in the detailed package insert that Xarelto is superior to warfarin. Among the reasons, it says such a claim "might induce physicians to switch patients who are doing well on warfarin to rivaroxaban."
Xarelto was approved in July for reducing the risk of deadly blood clots in patients getting knee and hip replacements, a small part of the potential patient pool. That approval followed a delay of roughly two years due to FDA concerns about internal bleeding risk _ a side effect listed on the package insert along with itching, muscle pain, blisters and fainting.
On Thursday, a panel of outside advisers to the FDA is to review data on use of Xarelto in patients with atrial fibrillation, including the staff report and a presentation by the makers. The advisers will then vote whether to recommend that the agency approve it.
They could urge an additional patient study be done, which would cause a long delay before the drugmakers could again seek approval. FDA officials often follow advisers' recommendations, but aren't obligated to do so.
"We now see a first-time approval as being unlikely," Jerffries Research analyst Jeffrey Holford wrote to investors. He noted the staff comments "point to poor clinical trial design."
"We're confident in the effectiveness of rivaroxaban in preventing strokes in patients with atrial fibrillation and look forward to presenting our data to address the FDA's questions on Thursday," said Johnson & Johnson spokesman Ernie Kniewitz. "In our book, we've laid out a lot of points that support the effectiveness of rivaroxaban."
Bayer Healthcare already markets rivaroxaban in 110 countries around the world.
The daily pill works by blocking a clotting protein called factor Xa. Older blood thinners, including warfarin, work by preventing platelets from sticking together.
Warfarin, sold as Coumadin and other brands, has its own drawbacks. It's notoriously difficult to get the dose of the drug correct, so patients need frequent blood tests because too much warfarin can cause dangerous internal bleeding.
That's made a replacement for inexpensive warfarin a key goal for numerous drugmakers. Last October, the FDA approved the first alternative to warfarin for atrial fibrillation _ Pradaxa, known chemically as dabigatran, made by the German company Boehringer Ingelheim.
The FDA staff report states that the large RE-LY study used to get approval for dabigatran showed it clearly was superior to warfarin in preventing stroke and dangerous blood clots. But ROCKET did not prove that was true for Xarelto, the report states.
"It seems advisable to make rivaroxaban a third-line agent, behind both warfarin and dabigatran," the report adds.
In late trading, Johnson & Johnson shares were up 40 cents at $64.47.