Takeda Threatens to End Orexigen Partnership Over Stopped Obesity Study
May 13, 2015
By Alex Keown andRiley McDermid, BioSpace.com Breaking News Staff
TOKYO – Early release of cardiovascular trial data for an obesity drug is at the core of Takeda Pharmaceuticals ’s threat to end a collaborative partnership with Orexigen Therapeutics, Inc. , the company confirmed Wednesday.
Earlier this week Takeda sent a dispute letter to Orexigen seeking to end collaboration over development of obesity drug Contrave, which was co-developed by both companies, due to the company’s “breach of the agreement,” a Takeda spokesperson told Bloomberg, who first reported the news. In its formal dispute, Takeda is seeking a new trial fully-funded by Orexigen, which could cost as much as $200 million.
Orexigen said the dispute with Takeda will likely be resolved in arbitration, but in a statement, asserted that Takeda’s claims are without merit.
“Further we intend to vigorously defend all of our rights and remedies, and assert any counterclaims that we have against Takeda,” Orexigen said.
Although the company hopes to vindicate itself for the data release, the company stock took a big hit, dropping from a high of $6.93 per share on May 12, the day the partnership was terminated, to today’s low of $5.48 per share.
Contrave was approved for use in extremely overweight individuals in 2014 by the U.S. Food and Drug Administration (FDA). According to the FDA Contrave is a combination of two FDA-approved drugs, naltrexone and bupropion, in an extended-release formulation. Naltrexone is approved to treat alcohol and opioid dependence. Bupropion is approved to treat depression and seasonal affective disorder and as an aid to smoking cessation treatment. Following approval the FDA required a new cardiovascular outcomes trial as a post-marketing requirement for the “evaluation of the effects of long-term treatment with Contrave on the incidence of major adverse cardiovascular events in overweight and obese subjects with CV disease or multiple CV risk factors,” Orexigen said.
The partnership has been a rocky one, after Orexigen was slapped by regulators for violations early this year. In March Orexigen released information related to the Light Study, a study of approximately 9,000 overweight and obsess patients with certain cardiovascular risks. The preliminary information released from 25 percent of the study appeared to show a reduction in heart-related deaths in patients taking the drug. After the information was released ahead of schedule, federal regulators said the early release damaged the integrity of the trials.
The Cleveland Clinic, which led the steering committee for the Light Study, said at the time of Contrave’s approval last year the FDA “determined that Orexigen had violated the terms of a data access agreement by revealing the 25 percent interim results to both a wide group of individuals within the company and external business partners.”
Data released by the Cleveland Clinic from the next 25 percent of the study earlier this week showed 55 cases of heart attacks, strokes and cardiovascular deaths in patients taking Contrave, compared with 43 in the placebo group.
“These results do not confirm cardiovascular benefits of Contrave claimed by Orexigen in the patent application based on the data obtained at the 25 percent time point in the trial,” Steven Nissen, chair of the study’s executive steering committee and chair of cardiovascular medicine at Cleveland Clinic, said in a statement. “The inconsistency of effects on cardiovascular outcomes between the first 25 percent and the second 25 percent 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.”
In the wake of the collapse of the collaboration and the Light Study, Orexigen has sought to right what it said were inaccuracies reported in the media. The company said it never misled patients involved in the study, nor did it mislead investors.
“At the time of the patent issuance in March, we stated plainly and clearly that the effect of Contrave on CV morbidity and mortality has not been established and that a larger number of MACE are required to precisely determine the effect of Contrave on CV outcomes,” the company said in a statement.
Takeda certainly has the resources to take its business elsewhere, should it choose to do so. In January, the first foreign chief executive of Takeda said he is open to large deals that will help Japan’s largest drugmaker reconfigure its focus and streamline its operations, Christophe Weber told Reuters, and said he’s been busy undertaking a “major review” of all of the firm’s businesses.
"We don't want to be passive and we don't want to watch the train passing," Weber told Reuters at the World Economic Forum in Davos, Switzerland this week. Originally lured away from GlaxoSmithKline last April, Weber became COO in June and is the incoming CEO for the 230-year-old Japanese company.
"Organically, we are doing okay, but I wouldn't mind doing a few deals," Weber said. "Perhaps a deal would be small or perhaps big. It depends what is out there."
He told Reuters he’s used the last nine months to drill down into Takeda’s infrastructure and has pinpointed three key area’s that will receive the most focus: emerging markets, GI therapies and oncology.
"Now we are in a better position to be active externally, which we want. We have zero net debt at Takeda, so we have some room for maneuver," he said. Referring to Takeda’s acquisition of American biotech Millennium, which it now has bringing in around $3 billion annually, Weber said he’d be open to similar deals that allow the company to reach new markets.
Chief among these is India, which Weber sees as a major driver for growth for Takeda moving forward, particularly in the oncology and GI spaces.
"We have now established a presence there to understand the market better,” he said. “It's a difficult market, very competitive and relatively low-margin, but we cannot ignore India.”
Weber also told Reuters that he’d been approached to take the top job at Sanofi but had declined.
“I’m committed to Takeda,” said Weber . “I just arrived and I’m not the kind of guy who would jump like that. It’s a unique opportunity at Takeda and I’m very committed to it.”