Higher bleeding risk seen in J&J, Bayer clot drug

A blood clot preventer from Johnson & Johnson and Bayer caused a surprisingly high rate of bleeding in a trial of patients with acute illnesses, representing a significant setback for the drugmakers.

Bayer AG.shares were down 2.8 percent at 55.15 euros in Frankfurt. J&J shares were off 0.8 percent at $59.65 on the New York Stock Exchange.

Industry analysts had predicted the trial of rivaroxaban, if successful, would create a potential $2.8 billion-a-year market opportunity for the medicine among the vast patient population represented in the study.

“This will surely impact the chances of admission of the drug and is a serious disappointment,” said Markus Huber, a senior trader at ETX Capital, adding that it could have serious financial repercussions for Bayer.

Other industry analysts said that the trial results do not preclude other big opportunities for the drug, which is already sold in Europe by Bayer under the brand name Xarelto to prevent blood clots in patients undergoing hip and knee surgery.

The drugmakers are developing the pill for other uses with a high sales potential, such as preventing stroke in patients with an irregular heartbeat called atrial fibrillation.

“There is disappointment given the recent (Bayer) share price rally and expectations that this was going to start off a positive run of news flow,” said Emmanuel Papadakis at Collins Stewart in London. “But this is a small subset of Xarelto’s total market opportunities.”

Development of new blood clot preventers has been one of the hottest areas in cardiology. Several pharmaceutical companies are vying to come up with a drug of choice to replace decades-old warfarin and other medicines.

Potential rivals to rivaroxaban include apixaban by Pfizer Inc and Bristol-Myers Squibb, edoxaban from Japan’s Daiichi Sankyo and Pradaxa, already being sold by privately-held Boehringer Ingelheim.

BLEEDING RISK

The 8,101-patient study released on Tuesday compared the bleeding risk and effectiveness of rivaroxaban with that of the standard injectable treatment enoxaparin in patients hospitalized for acute medical conditions, including heart failure, infectious disease and breathing difficulty.

Injections of enoxaparin, sold by Sanofi-Aventis under the brand name Lovenox, are typically given in the hospital, with treatment lasting no more than two weeks.

After 10 days of treatment in the study, rivaroxaban and enoxaparin were deemed equally effective in preventing dangerous blood clots in the extremities and in the lungs.

Although enoxaparin is not typically used for long periods, J&J wanted to assess its long-term effectiveness compared with rivaroxaban. To set up a comparison, patients took enoxaparin for 10 days, and then took placebos for the subsequent 25 days, while rivaroxaban was given for 35 days.

By that measurement, rivaroxaban proved significantly more effective than enoxaparin.

Although enoxaparin is not typically used for long periods, J&J wanted to assess its long-term effectiveness compared with rivaroxaban. To set up a comparison, patients took enoxaparin for 10 days, and then took placebos for the subsequent 25 days, while rivaroxaban was given for 35 days.

By that measure, rivaroxaban proved significantly more effective than enoxaparin.

But patients taking the J&J/Bayer drug had a significantly higher rate of bleeding. Some 2.8 percent of patients taking rivaroxaban had clinically relevant bleeding at 10 days, compared with 1.2 percent of those receiving enoxaparin, a difference that was highly statistically significant.

At 35 days, 4.1 percent of the rivaroxaban group experienced bleeding, versus 1.7 percent taking enoxaparin.

“This is a setback for rivaroxaban because its efficacy is counterbalanced by the risk,” said Dr. Catalin Balan of the University Emergency Hospital in Sibiu, Romania, who was not involved in the trial. “It worsens the overall view of the drug.”

Lead researcher Alexander Cohen of King’s College Hospital in London said the drug fell short because safety was assessed not only by major or fatal bleeding, but also by minor bleeding such as nosebleeds where the patient called a doctor, big bruises and blood in the urine.

Had the trial only included serious bleeding, he said the benefit of rivaroxaban would have outweighed its risks. Seven patients taking rivaroxaban died from major bleeding, versus one for enoxaparin. But 30 patients taking enoxaparin died from lung clots, versus 19 taking the J&J drug.

Peter DiBattiste, vice president of cardiovascular development for J&J, said the company will conduct additional analyses to see if rivaroxaban can be used more selectively in patients hospitalized with acute medical illness.

DiBattiste said that compared to enoxaparin, a higher bleeding risk was not seen for his drug in earlier successful trials among patients undergoing orthopedic surgery.

“This is a different population than we’ve seen before, with different organ systems involved,” he said. “And they’re probably more predisposed to bleeding because of multiple illnesses and multiple medicines.”

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By Ransdell Pierson

NEW ORLEANS