Otsuka Holdings Co., Ltd.

RSS Tweet Share Otsuka Pharmaceutical Co., Ltd. (Otsuka) and H. Lundbeck A/S (Lundbeck) announce that Otsuka has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding the supplemental New Drug Application (sNDA) for use of REXULTI® (brexpiprazole) in combination with sertraline for the treatment of adults with post-traumatic stress disorder (PTSD). The CRL states that the FDA has completed their review but cannot approve the application in the current form, further stating that the application does not provide substantial evidence of effectiveness to support the approval. The sNDA for brexpiprazole in combination with sertraline for the treatment of adults with PTSD was accepted for review by the FDA in June 2024 and was based on data from three randomized clinical trials that evaluated the safety and efficacy of brexpiprazole in combination with sertraline in adult patients with PTSD. The FDA decision follows a meeting of the Psychopharmacologic Drugs Advisory Committee on July 18, 2025. The committee voted 1-10, determining that the efficacy of brexpiprazole, when initiated concurrently with sertraline, has not been established for the treatment of PTSD based on the available data presented. Although data from three clinical studies were submitted, the FDA stated in the CRL that not all of these studies are capable of contributing to the substantial evidence of the submission and should Otsuka and Lundbeck be interested in proceeding with the indication, additional positive, adequate and well-controlled trials would be needed to provide substantial evidence of effectiveness. "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," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka. "Otsuka and Lundbeck will take time to review the contents of the letter with the FDA to determine the appropriate path forward." Johan Lutham, executive vice president of Lundbeck Research & Development, commented, "Post-traumatic stress disorder places a significant and often overlooked burden on patients, their families, and society. We are grateful to the participants, their families, the clinical trial site investigators and staff, and the entire program team for their dedication and commitment to advancing care for those living with PTSD." About Brexpiprazole Brexpiprazole was approved in the U.S. by FDA in 2015, as an adjunctive therapy to antidepressants in adults with major depressive disorder (MDD) and as a treatment for schizophrenia in adults. Most recently, brexpiprazole was approved in the U.S. for the treatment of agitation associated with dementia due to Alzheimer's disease, in May 2023. Brexpiprazole has also been approved in more than 60 countries worldwide, including the European Union, Canada and Japan. Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck. The mechanism of action of brexpiprazole is unknown. Brexpiprazole has high receptor binding affinity to norepinephrine, serotonin and dopamine receptors. It is an antagonist at norepinephrine α1B and α2C receptors and serotonin 5-HT2A receptors, as well as a partial agonist at serotonin 5-HT1A and dopamine D2 receptors.

RSS Otsuka Pharmaceutical Co., Ltd. (Otsuka) announces that the Japanese Ministry of Health, Labour and Welfare（MHLW）has approved NEXLETOL®（bempedoic acid） for the treatment of hypercholesterolemia and familial hypercholesterolemia. NEXLETOL is an oral, non-statin treatment with a novel mechanism of action. It inhibits ACLY (adenosine triphosphate citrate lyase), an enzyme upstream of the statin target in the liver's cholesterol synthesis pathway, which ultimately leads to a reduction in blood LDL-cholesterol levels. NEXLETOL was created by Esperion Therapeutics, Inc. (Esperion). NEXLETOL is marketed as a treatment for hypercholesterolemia in several regions around the world, including the United States and Europe. In 2020, Otsuka acquired exclusive development and commercialization rights for NEXLETOL in Japan from Esperion and has been advancing its development. (https://www.otsuka.co.jp/en/company/newsreleases/2020/20200420_1.html) Some patients with hypercholesterolemia are unable to achieve their target cholesterol levels despite taking statins (insufficient response to statins), while others find it difficult to continue treatment with statins due to adverse events. NEXLETOL is expected to offer a new therapeutic option for these patients in Japan. A Phase 3 trial (NCT05683340) was conducted in Japan as a placebo-controlled, randomized, multicenter, double-blind, parallel-group comparative study, in 96 patients with high LDL cholesterol and in whom statins had insufficient effect or whom statin therapy is not suitable. Trial participants were orally administered either 180 mg of NEXLETOL or a placebo once a day, for 12 weeks to evaluate the efficacy and safety of NEXLETOL. The percentage change from baseline in LDL-C at Week 12, the primary endpoint, was -25.25% in the group receiving NEXLETOL group and -3.46% in the placebo group, demonstrating positive outcomes with statistical significance compared to placebo (p<0.001). Furthermore, the safety and tolerability of NEXLETOL were favorable, and no serious adverse events were observed. About Otsuka Otsuka Pharmaceutical Co., Ltd. is a total healthcare company that focuses on each individual's potential to enhance their well-being. Our medical-related business provides treatments and diagnostics for both physical and mental health. Our nutraceutical business supports daily health maintenance and improvement. Otsuka's unique products and services are based on scientific evidence, under the guidance of our corporate philosophy: Otsuka-people creating new products for better health worldwide. For further information, please visit www.otsuka.co.jp/en/

iStock, Anton Vierietin VectorY Therapeutics will evaluate the use of SHP-DB1, a capsid developed by Shape Therapeutics, to deliver therapies to the brain, including VectorY’s developmental Huntington’s and Alzheimer’s disease treatments. VectorY Therapeutics is joining with Shape Therapeutics in an option-and-license agreement worth potentially north of $1 billion. The deal, announced Thursday, gives VectorY the option to evaluate Shape’s adeno-associated virus (AAV) capsid called SHP-DB1, developed to penetrate and deliver therapies deep into the brain. As per terms of the partnership, VectorY will assess the capsid’s ability to deliver antibody payloads for three therapeutic targets. If the evaluation is successful, VectorY can obtain an exclusive license for SHP-DB1. A specific financial breakdown of the agreement was not provided in the announcement , but Shape is entitled to an upfront payment, plus a potential $1.2 billion in fees and milestones. Upon VectorY exercising its option, Shape will be eligible for regulatory, development and commercial milestones that could hit up to $338 million for rare disease applications and $503.5 million for non-rare disease programs. The collaboration will enable intravenous administration of programs already in the company’s pipeline, according to VectorY, including VTx-003, an antibody targeting mutant huntingtin (mHTT) and TDP-43 for treating Huntington’s disease, as well as VTx-005, an antibody against phosphorylated tau for Alzheimer’s disease. SHP-DB1 is an engineered AAV capsid, which according to the companies’ announcement, is designed to “overcome the limitations of naturally occurring AAV serotypes.” The engineered capsid can penetrate deep into the brain while avoiding liver and dorsal root ganglion toxicities that are a concern for other AAV vectors. Two deaths associated with Sarepta’s Elevidys, for example, were due to acute liver failure, as was the death of a patient in a clinical trial for an investigational limb-girdle muscular dystrophy gene therapy. These developments prompted some experts to look beyond AAVs as delivery vehicles for this type of therapy. “We designated AAV5 as our capsid of choice from the company founding,” VectorY CEO Jim Scibetta said in a statement announcing the deal, “and are deploying an AAV5 capsid in our lead asset, VTx-002, a TDP-43 motor neuron (non-deep brain) targeting vectorized antibody for ALS,” for which the company plans to investigational new drug application by the end of 2025. Shape has done multiple deals over the years to leverage tech developed in-house. In 2023 , the company linked with Otsuka in a deal worth up to $1.5 billion, where Otsuka gained access to Shape’s AI-developed AAV capsid discovery platform. Two years earlier, in 2021, Shape partnered with Roche in a pact valued at more than $3 billion, in which the Swiss pharma would use Shape’s RNA editing and AAV technology to develop gene therapies.