J&J, Bayer’s Xarelto Curbs Clots, Raises Bleeding Risk in Clinical Study
By Michelle Fay Cortez and Naomi Kresge - Apr 5, 2011
Johnson & Johnson and Bayer AG (BAYN)’s experimental pill Xarelto worked as well as a standard injection to prevent blood clots from forming in critically ill hospital patients, though it raised bleeding rates in a study.
A second analysis found giving Xarelto for more than 10 days cut clots in the legs and lungs by 23 percent, according to the study, which was presented today at the American College of Cardiology’s annual meeting in New Orleans. Longer use more than doubled the risk of major bleeding compared with patients given a placebo after the standard 10 days of treatment with Sanofi- Aventis SA’s Lovenox.
Johnson & Johnson is evaluating the findings and hasn’t decided if it will file for marketing approval for hospitalized patients based on the results, said Peter DiBattiste, vice president of cardiovascular development at the New Brunswick, New Jersey-based company. Doctors at the meeting said they are eager for the drug because patients immobilized in the hospital are at high risk, especially after they are discharged.
“When very sick patients seem to be recovering, nothing is worse than a setback with a pulmonary embolism or deep vein thrombosis” caused by blood clots that lodge in the lungs or legs, said Richard Becker, director of Duke University’s cardiovascular thrombosis center in Durham, North Carolina. “This may be a way to temper that risk,” said Becker, who wasn’t involved in the study.
Xarelto, which is awaiting U.S. regulatory approval for preventing strokes in heart patients and clots after surgery, may generate $640 million in sales worldwide by 2015 for sick hospital patients, said Jack Scannell, an analyst with Bernstein Research in London, in a March 31 note to investors. Sanofi’s Lovenox, which is losing patent protection, generates about 1.4 billion euros ($2 billion) for the same group, he said.
Sales Forecast
The findings don’t change Bayer’s forecast that Xarelto will bring in more than 2 billion euros in annual sales, said Frank Misselwitz, head of Bayer’s cardiovascular unit, in an interview. The partners are in discussions with the European Medicines Agency in London and other regulators, he said.
The study involved 8,101 patients with limited mobility because of infections, heart failure, breathing difficulties, stroke and cancer. The lack of movement during a hospital stay puts patients at an 8-fold increased risk for blood clots, according to Johnson & Johnson (JNJ), and those patients account for almost one-quarter of the potentially deadly clots.
More than 200,000 people in the U.S. develop the clots known as venous thromboembolism each year, according to the Dallas-based American Heart Association. Nine percent of those with clots in the legs die within a month, as do 15 percent with clots that lodge in the lungs, according to a 2004 study in the American Journal of Medicine.
Magellan Trial
The new trial, dubbed Magellan, found 2.7 percent of patients getting either Xarelto or Lovenox for 10 days developed a blood clot or died as a complication of one. Almost all of the clots were found using ultrasound scans before they started causing symptoms. Bleeding that required medical care occurred in 2.8 percent of Xarelto patients, compared with 1.2 percent of those taking Lovenox.
After 35 days of Xarelto, 4.4 percent of patients had the clots, compared with 5.7 percent of patients who got Lovenox for 10 days, then placebo. The bleeding risk was 4.1 percent with Xarelto, compared with 1.7 percent for the Lovenox group. Most of the bleeding was detected with laboratory tests rather than symptoms, or stemmed from the need for a transfusion. Johnson & Johnson is trying to identify patients who may be at higher risk for bleeding to help control the unwanted effects, DiBattiste said in an interview.
‘Deeper Dive’
“We have demonstrated efficacy and we want to understand better how the risks and benefits play out,” he said. “We need to do a deeper dive.”
When researchers designed the trial three years ago, they considered it a “blue-sky scenario” to think all patients would require Xarelto, Misselwitz said. “This was quite a realistic outcome that only certain patients would require it.”
It’s not clear if giving patients drugs like Xarelto or competing medicines called anti-coagulants for longer periods will be beneficial, said Robert Califf, a cardiologist and vice chancellor for clinical research at Duke University Medical Center in Durham, North Carolina. It’s not the current standard of care, he said in an interview.
“I don’t think many people are going to rush out to start anti-coagulants in patients with pneumonia or acute respiratory distress syndrome,” said Califf, who has conducted other studies of Xarelto. “But it’s a big market and mortality rates are high.”
Overlooked Study
The study has been overlooked by the market, said Jeffrey Holford, an analyst at Jefferies International Ltd. in London, in a March 20 note to investors. Preventing clots in critically ill patients could generate peak sales of as much as $1.3 billion, including $800 million for Bayer, he said. The drug’s biggest potential stems from preventing strokes in people with erratic heart rates, with $2.8 billion in peak sales, he wrote.
The results of the Magellan study, if positive, may be used to apply for regulatory approval of Xarelto for medically ill patients within six months, with potential approval in the first quarter of 2012, Holford said in the note.
To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net
