Orexigen Therapeutics on Tuesday terminated a required cardiovascular outcomes trial for its obesity drug Contrave amid controversy over the publication of interim results that the lead trial researcher called misleading and unreliable.
The 9,000-patient trial was being conducted at the Cleveland Clinic and lead by cardiologist Steven Nissen. In March, Orexigen released interim data from the trial suggesting that the drug did more than help patients lose weight; it also reduced the risk of heart attack, stroke, and cardiovascular disease deaths by 41%.
Study: These six activities could prevent 70% of heart attacks
Shortly after the company released the data, Nissen objected to the early announcement, saying the data was premature and not reliable. John Jenkins, the head of the FDA's Office of New Drugs, agreed with Nissen.
This week, Cleveland Clinic issued a press release in which Nissen offered data to support his objection to the interim study findings.
Specifically, the new data showed that the heart benefit nearly disappeared and became statistically insignificant as the trial progressed. Moreover, the data suggested that Contrave patients were more likely to experience chest pains or die for reasons not related to heart disease.
Johns Hopkins IDs a new risk of obesity: 'silent heart damage'
"Patients were misled, investors were misled," says Nissen. "It is so critically important that investors and other people understand why early data in a trial are unreliable or unstable."
FDA approved the drug in September 2014, but the label said the drug's effects on cardiovascular morbidity and mortality had not been determined. But later, the Securities and Exchange Commission issued Orexigen a patent for using Contrave for cardiovascular purposes. The filing for the patent included details of the ongoing trial—a disclosure that Nissen says was forbidden by the terms of the study.
More broadly, Nissen warns, "The inconsistency of effects on cardiovascular outcomes between the first 25% and the second 25% of the Light Study clearly illustrates the risks inherent in pre-judgment of clinical trial results based upon an interim analysis and demonstrate why interim results should remain confidential during any ongoing trial."
Orexigen has not commented on the new data, but it says it did not mislead patients or investors when it released data earlier this year.
The jobs that are hardest on your heart
The company expects to begin a new trial later this year, with a target completion date of 2022. Nissen says the now-terminated study would have finished in 2017 (Herper, Forbes, 5/12; Chen, Bloomberg Business, 5/12; Beilfuss, Wall Street Journal, 5/12; O'Riordan, Medscape Medical News, 5/12).
Next in the Daily Briefing
Report: NYC hospitals poised for $1B deficit—and ACA cuts will make it worse