Orexigen Therapeutics said Tuesday it has terminated a required
cardiovascular outcomes trial of its obesity drug Contrave, after
prematurely releasing interim study results in March.
The company noted that the study isn't being terminated because
of the finding of superiority or harm. A new trial is expected to
begin later this year and has a target completion date of 2022,
Orexigen said.
Last September, Orexigen and its Japanese partner Takeda
Pharmaceutical Co. received approval to market Contrave from the
U.S. Food and Drug Administration. At the time, Contrave's label
said the drug's effect on cardiovascular morbidity and mortality
had not been established and warned of increased blood pressure and
heart rate.
The FDA had approved the drug on the condition that the
companies complete several post-marketing trials, including a
long-term cardiovascular study known as Light.
Six months later, Orexigen unexpectedly disclosed interim data
of the study. The 9,000-patient trial was designed to assess the
extent to which the drug may increase the risk of a major cardiac
event, but interim results indicated the drug may actually reduce
cardiovascular risks compared with a placebo. The company, in a
filing with the Securities and Exchange Commission, noted it was
issued a patent for using its Contrave diet drug to prevent
cardiovascular events and that the patent included details of the
continuing study.
Orexigen shares jumped 32% on the news.
The FDA said it wasn't the first time Orexigen had
inappropriately disclosed Light study data and required the company
to begin a new trial later this year. Steve Nissen, a cardiologist
at the Cleveland Clinic who was the lead researcher for the study,
at the time said the disclosure of the incomplete data "was
strictly forbidden."
On Tuesday, Orexigen and Takeda said they have accepted the
recommendation of Dr. Nissen for the early termination of the Light
study.
In a separate statement, Dr. Nissen said the Light study results
"do not confirm cardiovascular benefits of Contrave claimed by
Orexigen in the patent application based on the data obtained at
the 25% time point in the trial."
Dr. Nissen added that the results show neither benefit nor harm,
"but are consistent with the requirement by the FDA that the Light
Trial demonstrate an absence of a doubling of cardiovascular risk
for patients taking the drug."
"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 prejudgment of clinical trial
results based upon an interim analysis and demonstrate why interim
results should remain confidential during any ongoing trial," said
Dr. Nissen, who will lead the new study.
Orexigen and Takeda in 2010 entered into a partnership to
develop and commercialize Contrave, after Orexigen submitted a New
Drug Application to the FDA. Orexigen and rivals Arena
Pharmaceuticals Inc. and Vivus Inc. tried for years to win approval
of their diet drugs. Contrave was initially rejected in 2011;
Arena's Belviq and Vivus's Qsymia won approval in 2012.
Contrave is a combination of two drugs already on the market:
addiction-treating naltrexone and the antidepressant bupropion,
commonly known by the brand name Wellbutrin. In the first quarter,
Takeda reported Contrave U.S. net sales of $11.5 million, for which
Orexigen earned $2.3 million in royalties.
Shares in the company, up 13% this year, fell 0.9% in morning
trading.
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