Pfizer Inc. and Bristol-Myers Squibb Co.’s experimental drug apixaban wasn’t safer or more effective than a standard treatment in stopping blood clots in the legs and lungs of patients after hospitalization, a study found.
The trial, reported today at the American Heart Association meeting in Orlando, Florida, is the second to show new anticoagulants don’t provide a benefit in severely ill patients more than Sanofi’s injected drug Lovenox, the current standard. Johnson & Johnson and Bayer AG’s Xarelto failed to beat the standard therapy in a trial reported last April.
The potentially deadly clots occurred in 2.7 percent of those given apixaban, also known by the brand name Eliquis, compared with 3.1 percent of those given Lovenox, the results showed. The difference wasn’t statistically significant, researchers said. While the drugs’ benefits increased over time, both also triggered more major bleeding.
“We’ve made great headway in preventing deep vein thrombosis and pulmonary embolism in surgical patients and hospitalized medical patients,” said lead author Samuel Goldhaber, director of the venous thromboembolism research group at Brigham and Women’s Hospital and professor at Harvard Medical School, in a statement. “Where we have failed to make progress is the after-hospital discharge medical patient.”
8 Million Patients
There are about 8 million U.S. patients a year that are at moderate to high risk of venous thromboembolism, Goldhaber said. About 1 percent of patients develop symptoms from the clots after they are released from the hospital, and they are most common in the following three months, said Mary Cushman, director of the thrombosis program at the University of Vermont.
Pfizer, the world’s biggest drugmaker, and Bristol-Myers are both based in New York. The companies are evaluating the results and haven’t decided what their next steps will be, said MacKay Jimeson, a Pfizer spokesman.
Researchers in the apixaban study and earlier trial of Xarelto, made by New Brunswick, New Jersey-based Johnson & Johnson, and Bayer, of Leverkusen, Germany, were looking to see if longer treatment with the new pills could cut death rates and prevent complications from leg clots that occur in as many as 600,000 Americans each year.
Hospitalized patients, such as those with pneumonia or heart failure, are at high risk for the clots.
The chance of success in the study was slim given the difficulty of treating such sick patients, especially after the Xarelto setback, said Seamus Fernandez, an analyst with Leerink Swann & Co. in Boston, in a Nov. 4 note to investors.
Apixaban is in development to prevent stroke in patients with atrial fibrillation, an erratic heartbeat that occurs in 2 million Americans a year. If approved, it will compete against Xarelto and Boehringer Ingelheim GmbH’s Pradaxa in a market estimated to top $10 billion in annual sales.
Analysts predict apixaban may take the lead after a study presented in August found it reduced deaths and bleeding rates more than warfarin, a form of rat poison used to treat the condition for more than five decades, unlike its rivals.
“Afib is clearly the primary indication for apixaban,” said Marc Goodman, an analyst at UBS AG in New York, in a note after the results were released. While the drug was forecast to generate about $100 million in 2015 for medically ill patients, the results should have “no meaningful impact” on the companies’ shares or the drug’s eventual sales, he said.
In hospitalized patients, the risk of the dangerous clots were lower with apixaban as the trial progressed and patients stopped getting Lovenox, which was given for longer than patients now get it in routine care, Goldhaber said. That raises the possibility that another study may find a benefit, he said.
“There is no question this is a tremendous opportunity to design and carry out a new trial,” he said in an interview. “I have been in this field for 30 years, and I have no doubt that it is going to happen.”
Bleeding occurred in 7.73 percent of patients on apixaban, up from 6.81 percent of those given Lovenox. Major bleeding was 2.5-fold higher in patients given apixban, occurring in 0.47 percent of those given the experimental drug versus 0.19 percent of those on Lovenox.
The increased risk of major bleeding poses a problem since few patients released from the hospital will ultimately develop symptoms from the clots, which the drug was designed to prevent, said Cushman from the University of Vermont. Cushman, who wasn’t involved in the trial, reviewed the findings at a press conference at the heart meeting.
The study was funded by Pfizer and Bristol-Myers and published in the New England Journal of Medicine. Johnson & Johnson, maker of Xarelto with Germany’s Bayer, is based in New Brunswick, New Jersey.