Paroxetine Hydrochloride

Rexulti’s PTSD snub was largely expected after an overwhelmingly negative vote on the drug’s approvability at an FDA advisory committee meeting in July. Following a negative FDA advisory committee vote earlier this year, the other shoe has dropped for Lundbeck and Otsuka Pharmaceutical’s post-traumatic stress disorder (PTSD) hopeful.The FDA has issued a complete response letter to the partners, scuppering their ambition to launch the atypical antipsychotic Rexulti—in combination with Viatris’ Zoloft (sertraline)—as a novel treatment for PTSD, Lundbeck and Otsuka said in a Sept. 20 press release.In the regulator’s letter, the FDA said it completed its review of the Rexulti application but could not currently approve it, citing a lack of substantial evidence of effectiveness in PTSD, according to Lundbeck and Otsuka.The partners used three separate phase 3 trials to support their application, which the FDA accepted for review last June.After its review, the FDA indicated to the companies that “not all of these studies are capable of contributing to the substantial evidence of the submission,” Lundbeck and Otsuka said in their release. Should the partners wish to continue pursuing a PTSD nod for Rexulti, they have been told they will need to run additional trials to establish stronger efficacy data.Both companies appear committed to Rexulti’s potential in the trauma-induced mental health condition, which is estimated to affect around 5% of the U.S. population, according to the National Center for PTSD.“While we respect the FDA’s decision, we continue to believe in the potential of Rexulti in combination with sertraline to help address this serious unmet need,” John Kraus, M.D., Ph.D., Otsuka’s EVP and chief medical officer, said in a statement. “Otsuka and Lundbeck will take time to review the contents of the letter with the FDA to determine the appropriate path forward.” The current treatment landscape for PTSD largely consists of the selective serotonin reuptake inhibitors (SSRIs) Zoloft and Paxil (paroxetine), both of which have had generic versions on the market for years.Rexulti’s PTSD snub was largely expected after an overwhelmingly negative vote on the drug’s approvability at an FDA advisory committee meeting in July. The panel of outside experts voted 10 to 1 against greenlighting Rexulti plus Zoloft in PTSD, arguing that the existing clinical data don't support the combo’s efficacy.In materials prepared ahead of the meeting, the FDA suggested that a “clearly and convincingly negative” phased 3 study had sewn doubts in reviewers' minds about the ability of the combination to demonstrate improvements over Zoloft alone.Otsuka and Lundbeck argued that Rexulti and Zoloft showed comparable reductions in the severity of PTSD symptoms across the three studies, while acknowledging that one of the trials failed to reach statistical significance. Rexulti holds approvals in three other psychiatric indications: major depressive disorder, schizophrenia and agitation associated with Alzheimer’s disease dementia.Lundbeck in February reported (PDF) total 2024 sales of Rexulti at 5.2 billion Danish kroner (about $822 million), an increase of 16% at constant currencies. The molecule was originally discovered by Otsuka before the Japanese pharma entered a co-marketing and development collaboration with its now longtime partner Lundbeck. 

Bengaluru: The U.S. Food and Drug Administration's panel of independent advisers on Friday voted against the efficacy of Otsuka Pharma's antipsychotic drug in combination with Viatris' antidepressant Zoloft for treating adults with PTSD. The panel voted 10-1 to say the available data does not establish the efficacy of the drug, brexpiprazole , in combination with Zoloft, chemically known as sertraline, for treating the condition. Its decision is in line with the FDA staff reviewers' assessment on Wednesday. Otsuka's application was based on the data from one mid-stage and two late-stage studies testing the combination treatment compared to sertraline plus placebo. It had failed to meet the main goal of significantly reducing severity of PTSD symptoms in one of the late-stage studies. PTSD, a disorder caused by very stressful events, affects about 4% of U.S. adults and is commonly associated with war veterans. But natural disasters, abuse or other trauma may also trigger the condition in civilians. "We simply cannot negate one negative study and say we are going to approve based on two other positive studies," said panelist Pamela Shaw, biostatistician at Kaiser Permanente. The advisers discussed possible side effects such as weight gain and movement disorders associated with long-term use of antipsychotics, but noted that the combination may be a better treatment option for patients who respond poorly to sertraline alone. "The big question for me is knowing that antipsychotics can cause real problems, especially with long-term use, and the modest benefit that the combination treatment potentially can offer," said panelist Walter Dunn, assistant clinical professor of psychiatry at University of California, Los Angeles. Otsuka said it would continue to work closely with the FDA as it completes its review of the application. The FDA, originally set to decide on the company's application by February 8, delayed its decision to seek the advisory panel's input. The agency has not set a new action date for the drug. The health regulator typically follows the advice of its expert advisers, but is not required to do so. If approved, the combination drug would be the first PTSD treatment to gain U.S. nod in more than two decades after Zoloft and GSK's Paxil. Brexpiprazole, branded as Rexulti and co-developed by Otsuka and Danish drugmaker Lundbeck, is approved in the U.S. to treat agitation in patients with the Alzheimer's disease and for adults with major depressive disorder and schizophrenia. (Reporting by Siddhi Mahatole and Mariam Sunny in Bengaluru; Editing by Shilpi Majumdar)