Orexigen has released a statement to reporters on the release of data from the largest study of is weight-loss drug, Contrave, by the Cleveland Clinic. The statement also comments directly on my earlier story, in which the study's lead investigator, Cleveland Clinic cardiologist Steven Nissen, said that Orexigen's refusal to publish data that undermined its earlier claims that Contrave might prevent heart attacks and strokes misled patients and investors. The statement was also read by Orexigen's chief executive, Mike Narachi, at the Bank of American Merrill Lynch Health Care Conference.
I'm going to print the entire 858 word statement, as well as a pair of shorter statements from Takeda, Orexigen's marketing partner in North America. But first I want to point out two pieces of news.
- Orexigen confirms that it disagreed with the academics who ran the clinical trial of Contrave about releasing data. The company says that it felt that the data should not be released until they had been fully vetted and analyzed after the closeout of the study. The academics, including Nissen, thought it was important to clear the record, because Orexigen had used an early cut of the data to argue that Contrave prevented heart attacks, strokes, and cardiovascular deaths and the new data did not support that conclusion.
- Orexigen also announced that, because the Food and Drug Administration will no longer accept the study because of the company's premature data release, Takeda has notified Orexigen that it has initiated a formal dispute process claiming material breach, and asking that Orexigen pay for the entire $200 million estimated cost of the new clinical trial that will have to be started to take the place of the one that was stopped today.
The full statements from both companies follow.
Orexigen statement:
This morning we and Takeda announced termination of the Light Study. We agreed with our partner, and together discussed our preferences with the U.S. Food and Drug Administration (FDA), that it was best to conclude the study in an orderly fashion, search for and gather all CV events and other safety data, have the CV events properly adjudicated, carefully analyze the final data and have these data presented and published in a scientific forum.
Since continuation of the Light Study was not a postmarketing requirement (PMR), and the majority of patients are no longer on blinded study drug, Orexigen had long advocated shutting down the study in December 2014, corresponding with the time of the 50% interim analysis, and focusing resources on new studies to further evaluate the therapeutic profile of Contrave.
We are pleased that the Light Study is now being terminated and want to thank the patients and all of those involved in the study. This trial has yielded important information about the safety profile for Contrave.
We have been informed that Takeda is on track to initiate a PMR cardiovascular outcomes trial (CVOT) later this year and recently achieved the first planned milestone with FDA acceptance of the study protocol in April.
Today some of the 50% interim analysis of the Light Study was disclosed by a third party. Because most of our management team remains blinded to the 50% data, we are unable to comment.
There have been a lot of challenges surrounding the use of interim data from ongoing studies for regulatory purposes. There are competing tensions for data confidentiality to preserve study integrity, transparency laws, and guidelines from regulatory bodies. With respect to the Light Study, Orexigen filed patent applications based on the unexpected result of the 25% interim analysis of LIGHT Study data. The first of those applications was granted and issued in March, and the full clinical study report that was submitted to FDA in the patent application was disclosed by the USPTO.
A few articles on this topic have been published in the media today that include misleading statements about our company. Contrary to allegations cited today by a journalist, Orexigen has never misled patients. 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.
Also contrary to the same story published today, Orexigen has not misled investors. Over the last 7 weeks, we have been working with the FDA, the Executive Steering Committee (ESC), the Data Monitoring Committee and Takeda to determine how, when and with what context the Light Study should be terminated. Takeda and Orexigen agreed that the appropriate manner to wind down the study was to collect the final information from the study and then to present and publish the study results. There was pressure from the ESC to release the 50% interim data. We maintained we would not be in a position to release data without access to the full data set, which we have not had and still do not have.
On another topic, we would also like to provide an update on Takeda. As you may recall we announced a non-binding term sheet at the time of approval as Takeda attempted to renegotiate the collaboration agreement. These discussions led to a previously disclosed non-binding term sheet. Since then, we have had the time to conduct our own diligence and the merits of Takeda’s claims, and have continued to negotiate the terms of an amended collaboration agreement. Today, Takeda initiated a formal dispute process claiming material breach. Takeda is seeking, among other things, Orexigen to pay the entire cost of the new cardiovascular outcomes trial.
As a result of this claim, Takeda and Orexigen will now enter into a dispute resolution process, which may include arbitration, unless our differences can be resolved otherwise. The protocol for dispute resolution is set out in the collaboration agreement.
We are currently evaluating the assertions made by Takeda and believe they are without merit. Further we intend to vigorously defend all of our rights and remedies, and assert any counterclaims that we have against Takeda.
As you know, cardiovascular safety has been a major issue in the obesity pharmacotherapy field. We look forward to the completion of the final analysis and publication once the Light Study is closed out and believe it can contribute important information about the overall safety profile of Contrave.
Takeda statement regarding the dispute letter:
Takeda sent a dispute letter to Orexigen on May 12 whereby Takeda seeks termination of its collaboration agreement (the “Agreement”) with Orexigen based on Orexigen’s material breach of the Agreement. Takeda is working closely with Orexigen to try to resolve the situation and avoid termination of the Agreement. As these discussions are ongoing, we cannot further comment.
Takeda statement regarding termination of Light study:
Takeda and Orexigen accepted the recommendation of the Executive Steering Committee, chaired by Dr. Steven Nissen of The Cleveland Clinic, for early termination of the Light Study, a cardiovascular (CV) outcomes trial that compared the obesity drug Contrave® (naltrexone HCI and bupropion HCl extended-release tablets) to placebo, in addition to diet and exercise counselling, in 8,909 overweight and obese patients with certain CV risk factors.
We believe that Contrave plays an important role in the treatment of obesity and Takeda stands behind the benefit/risk profile of Contrave. Takeda is committed to evaluating the effects of long-term treatment with Contrave on the incidence of cardiovascular events in overweight and obese patients with CV disease or multiple CV risk factors, as part of post marketing requirements.
There is no change to the indication of Contrave or its status on the market. Takeda strongly believes that Contrave helps to address a significant unmet need in the treatment of obesity and that it is an important medicine that can help patients reach weight loss goals.
