A study of an obesity drug has ended after the manufacturer released early and ultimately misleading data, researchers said on Tuesday.
The company, Orexigen Therapeutics, disclosed in March that early results from a clinical trial of its drug Contrave had shown a 41 percent reduction in the risk of heart attacks, strokes and death from cardiovascular causes. Orexigen’s stock shot up, and the information no doubt helped lift sales of Contrave.
But the academic researchers who oversaw the study said on Tuesday that Orexigen had violated an agreement that the early results were not going to be shared widely, even within the company.
Moreover, as participants in the trial were followed for a longer period of time, the benefit of the drug in reducing cardiovascular risks vanished.
The researchers, in a news release issued by the Cleveland Clinic, said they took the unusual step of terminating the study and releasing the more updated results.
“We felt it was unacceptable to allow misleading interim data to be in the public domain and be acted upon by patients and providers,” Dr. Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic and head of the trial’s steering committee, said in an interview.
He said Orexigen had “acted improperly and unethically in violating the data access agreement” and the premature release of data had made it difficult to continue the study.
It’s unlikley that patients would want to stay in the trial and risk getting a placebo if they thought the drug, which is already available on the market, could reduce their risk of heart attacks.
The Food and Drug Administration, citing similar reasons, has already ordered Orexigen to conduct another large study of the drug to rule out an increase in cardiovascular risk.
Orexigen said in a statement on Tuesday that it had wanted to shut down the older study in December. It also denied misleading anyone, saying that it had stated “plainly and clearly” that the data it released was preliminary and that the cardiovascular benefits of Contrave had not been established.
Contrave, which was approved in September, is one of four new prescription weight-loss drugs that have come to market since 2012, following more than a decade in which there were no new medicines.
Despite the fact that one-third of American adults are obese, the drugs have not sold well for a variety of reasons, including lack of coverage byMedicare and some insurers, modest weight loss, a history of safety problems with diet drugs, and a feeling among doctors and patients that obesity is not a disease.
Still, Contrave is off to a stronger start than the others, with United States sales of $11.5 million in the first quarter. The drug is closing in on Belviq, which has been on the market longer, for the lead in prescriptions, according to Simos Simeonidis, an analyst at RBC Capital Markets. Belviq was developed by Arena Pharmaceuticals and Eisai.
The F.D.A. declined to approve Contrave in 2011 because the drug slightly raised blood pressure and pulse rates, a sign that it might increase the risk of heart attacks and strokes. The agency told Orexigen to conduct a large study to rule out that risk.
Under agreement with the F.D.A., Orexigen looked at the data after 94 cases of heart attack, stroke or death from cardiovascular causes had occurred — about 25 percent of the expected total in the trial. Those early results effectively ruled out that Contrave doubled the risk of cardiovascular problems, clearing the way for the drug to be approved.
But in an agreement with the academic steering committee, the data was supposed to be known only by a small group within Orexigen charged with filing the application for F.D.A. approval.
Dr. Nissen said many more people were told. And when the company found out that those getting Contrave actually had a 41 percent lower risk of a heart attack, stroke or death from cardiovascular death, the company filed a patent application covering use of the drug to prevent cardiovascular problems.
When the patent was granted in early March, Orexigen disclosed this in a filing to the Securities and Exchange Commission, apparently viewing it as material to the company. The filing contained the preliminary trial results.
The company’s action drew an unusual rebuke from a senior F.D.A. official, who said in interviews that data from so early in a trial was very unreliable.
The steering committee said on Tuesday that as the trial continued, more patients getting the drug began having heart attacks and strokes, or died. After 192 adverse cardiovascular events the trail was halfway completed, and the earlier reported benefit was no longer statistically significant. There were 102 events in the placebo group compared with 90 among those who received Contrave.
Orexigen also said it was fighting with its marketing partner, Takeda Pharmaceutical in part over which company will have to pay for the new cardiovascular trial. Orexigen said Takeda had initiated a formal dispute process claiming a material breach of the agreement between the companies.
No comments:
Post a Comment