By Anna Yukhananov
COLLEGE PARK, Maryland (Reuters) - A new stroke preventer from Bayer and Johnson & Johnson moved one step closer to U.S. approval, but questions remained about restrictions on labeling and the need for more studies.
A Food and Drug Administration advisory panel voted 9-2 on Thursday to recommend approval of the once-a-day anti-clotting pill, called Xarelto.
Xarelto is one of several promising entrants angling to replace warfarin for people with dangerously irregular heart rhythms, called atrial fibrillation (AF).
Warfarin is a problematic decades-old clot preventer originally developed as rat poison.
"I've seen the problems many patients face with warfarin," said Dr. Philip Sager, a panel member and executive committee member of the Cardiac Safety Research Consortium in San Francisco. "I think there's a tremendous unmet medical need for new therapies."
Analysts estimate the stroke-fighting market could top $10 billion annually. Xarelto may lose out on market share if the FDA asks the company to conduct further trials, delaying approval, analysts said.
AF patients' irregular heartbeats can cause blood to pool, increasing their risk of blood clots and strokes. But many are unwilling to take warfarin, which requires regular blood tests, or are unable to tolerate it.
Panelists were divided on whether Xarelto, with the clinical name rivaroxaban, was as effective as warfarin.
In clinical trials that compared Xarelto to warfarin, panelists and the FDA said the older drug was not always given in the proper dosing, making it more difficult to determine if Xarelto was just as good.
"I've heard nothing that convinces me that rivaroxaban should be first-line treatment for many patients," said Allan Coukell, the consumer representative on the panel and director for medical safety at Pew Health Group, adding that Xarelto's label should reflect that.
Earlier this week, FDA reviewers said for conditions such as stroke, which can cause irreversible harm, new drugs must be shown to be at least as effective as older treatments, and called for the agency to delay Xarelto's approval.
In Thursday's meeting, panel members also focused on risks for patients when they come off the drug. Patients who stopped taking Xarelto and resumed warfarin at the end of the main clinical trial had a higher risk of stroke, a so-called "rebound" effect.
"Additional data probably should be obtained regarding how to transition (off of Xarelto) prior to approval," said Dr. Michael Lincoff, chair of the panel and professor of medicine at the Cleveland Clinic.
DELAY IN APPROVAL?
The FDA is set to make the final decision on Xarelto by November 4, Johnson & Johnson said.
"Given the relatively risk-adverse nature of the FDA, even with this panel's recommendation of Xarelto, the agency may want a number of additional studies" before granting approval, said Morningstar analyst Damien Conover.
"So there could be a one-to-two-year delay," he predicted, saying that would greatly hurt the drug's ultimate sales potential.
He said the FDA might be willing to take its time because another effective blood clot preventer, Boehringer Ingelheim's Pradaxa, was approved last year and is already available as an alternative to warfarin.
Conover said he had expected Xarelto to eventually capture 15 percent of the stroke-prevention market among AF patients, but he now expects its market share to be below 10 percent.
Dr Peter Dibattiste, global head of J&J's cardiovascular and metabolic division, said the company will discuss with the FDA the need for additional studies. A study looking at how long Xarelto lasted in patients could be relatively quick, "probably months," he told reporters.
A delay for Xarelto could give the edge to a rival treatment called Eliquis being developed by Bristol-Myers Squibb and Pfizer Inc. If Eliquis is approved, Morningstar's Conover predicted, it could have four times the sales of Xarelto.
Eliquis, also called apixaban, showed superiority over warfarin in effectiveness, safety and saving lives in a clinical trial presented last month at a scientific meeting in Paris, affirming its place as the potential leader of the pack.
Xarelto is approved in the United States and Europe for anti-clotting in patients after knee and hip surgery, a much smaller market than stroke prevention for AF patients.
Earlier this week, analysts from Sanford Bernstein forecast Xarelto sales of $948 million for J&J in 2015, and 800 million euros ($1.1 billion) for Bayer, which has much greater sales outside the United States.
Bayer said it sees peak sales of Xarelto at more than 2 billion euro ($2.8 billion), "irrespective of the decision by the FDA in early November," according to a statement.
Bayer, which co-developed the drug with J&J, sold exclusive U.S. marketing rights for Xarelto to J&J in 2005. As part of that agreement Bayer stands to receive royalty payments of up to 30 percent on U.S. sales.
Bayer said it expects approval of Xarelto in Europe in the third or fourth quarter of this year.
(Additional reporting by Ransdell Pierson in New York and Ludwig Baker in Frankfurt; editing by Bernard Orr, Gary Hill, Dave Zimmerman)
(This story corrects 10th paragraph to show Coukell is consumer representative, not patient representative)