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# Orexigen’s LIGHT Trial Ended Early, Results Unsure
- URL: https://www.fdaweb.com/orexigens-light-trial-ended-early-results-unsure/
- Published: 2016-03-08T12:00:00.000Z
- Updated: 2026-09-15T02:41:53.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5135007

> The LIGHT trial to determine whether the combination of naltrexone and bupropion increases major adverse cardiovascular events was terminated early after an unplanned release of confidential interim data by the sponsor (Orexigen) and the results “remain uncertain and will require evaluation in a new adequately powered outcome trial,” according to a [report](http://jama.jamanetwork.com/article.aspx?articleid=2499275&ref=fdaweb.com) in the *Journal of the American Medical Association*. The report notes that the combination of naltrexone and bupropion reduced weight during Phase 3 clinical trials, but FDA deferred approval based on safety concerns related to small increases in blood pressure and heart rate during the trials.  
>  
> The agency mandated a placebo-controlled, non-inferiority cardiovascular outcomes trial. Both the sponsor and FDA agreed not to disclose the 25% interim analysis until completion of the study. However, while the trial was ongoing, the sponsor publicly released the confidential 25% interim results via a patent publication. The study’s academic leadership recommended termination of the trial due to the breach of confidentiality and the sponsor agreed.  
>  
> Study authors say that FDA recently adopted a two-stage approach to drug approval with the intent of ruling out a high degree of hazard before approval based on an interim analysis of preliminary clinical trial results. “The success of the two-stage approach to drug development relies on the maintenance of strict confidentiality during the time from submission of the initial interim results until completion of the definitive safety study,” they write.  
>  
> Among overweight or obese patients at increased cardiovascular risk, the report says, based on the interim analysis performed after 25% and 50% of planned events, the upper limit of the 95% confidence interval of the hazard ratio for major adverse cardiovascular events for naltrexone-bupropion treatment, compared with placebo, did not exceed 2.0\. However, because of the unanticipated early termination of the trial, it says, it is not possible to assess noninferiority for the prespecified upper limit of 1.4.  
>  
> In an [editorial](http://jama.jamanetwork.com/article.aspx?articleid=2499259&ref=fdaweb.com), former FDA principal deputy commissioner **Joshua Sharfstein** discusses the agency’s two-stage approach and use of interim analyses. He notes that based on interim results, the sponsor filed a patent claiming a cardiovascular benefit for the combination drug. “The sponsor’s statements were highly misleading,” he says. “The interim analysis did not support the conclusion that the drug had a ‘positive effect’ on cardiovascular outcomes…. The LIGHT trial and the surrounding events also highlight how strong regulatory oversight is essential in the development and marketing of prescription drugs. The sponsor disregarded the multiple harms caused by serial breaches of confidentiality, treated the academic investigators unfairly, ignored the data monitoring committee, and defied FDA. Yet instead of receiving sanction, the sponsor won approval for its medication, was relieved of the obligation of paying for the rest of the LIGHT study, and gained the ability to market naltrexone-bupropion in the absence of final results of a cardiovascular safety study until the new study is completed, which is expected to be 2022.”  
>  
> Sharfstein calls on FDA to review its policy of permitting approval based on interim analyses of ongoing safety studies. “At a minimum,” he says, “when a company violates its commitment to confidentiality and FDA requires a new trial, the agency should delay approval at least until a viable replacement study is being conducted. If the drug has already been approved, FDA should use its authority to require Risk Evaluation and Mitigation Strategies to counter misinformation or restrict use of the medication as appropriate.”