Soticlestat

Takeda previously noted the “totality of the data” to make the case soticlestat had a future in Dravet. \n Takeda has axed plans to seek approval for its failed epilepsy drug candidate soticlestat. The Japanese drugmaker pulled the plug on the program after the FDA pointed out the shortcomings of its clinical data package.Soticlestat, a cholesterol 24 hydroxylase inhibitor, failed phase 3 trials in two forms of epilepsy last year. The studies showed the molecule was statistically no better than placebo at reducing the frequency of seizures in people with Lennox-Gastaut syndrome (LGS) and Dravet syndrome. Takeda soon removed the LGS program from its pipeline and reported a $140 million charge related to the molecule.Yet, Takeda noted the “totality of the data”—a favorite phrase of sponsors of failed trials—to make the case soticlestat had a future in Dravet. The FDA quashed Takeda’s hopes. According to Takeda, the U.S. regulator said the current data is incapable of showing substantial evidence of effectiveness in Dravet.Takeda uploaded the phase 3 data to ClinicalTrials.gov late last year. The update shows Dravet patients on soticlestat experienced a 22.16% reduction in convulsive seizure frequency per 28 days, compared to an 8.64% reduction in the placebo group. The difference fell short of statistical significance, yielding a p-value of 0.061. Takeda linked the drug candidate to nominally significant changes on six secondary endpoints, tracking positive shifts in responder rate, measures of caregiver and clinician global impression of improvement, and seizure intensity and duration scales over the 16-week treatment period. Coupled with the relatively narrow miss on the primary endpoint, Takeda thought the secondary measures could get it over the line.The company’s inability to convince the FDA of the strength of the data package has implications for Ovid Therapeutics and Ligand Pharmaceuticals. Ovid inked a deal with Takeda in 2021 and sold part of its royalty rights to Ligand in 2023. The failure of the phase 3 soticlestat trials sparked changes at Ovid, which would have been in line for milestones and royalties if the molecule had come to market. The removal of soticlestat wasn\'t the only change that Takeda revealed today. The company also announced that Julie Kim, president of Takeda’s U.S. Business Unit, will take over from CEO Christophe Weber when Weber retires in June 2026.

Several months into a multiyear quest to “rigorously prioritize” its pipeline, Takeda is cutting a handful of programs. The company revealed the changes on Thursday in its third-quarter earnings report , in which CEO Christophe Weber announced plans to retire in June 2026. Weber last year laid out the road map for a broad restructuring aimed at simplifying the company’s structure, removing layers and broadening roles. Takeda has also made several pipeline cuts over the last year, and it’s now ending work on a Phase 3 program for soticlestat in a form of epilepsy. In 2024, soticlestat failed separate Phase 3 trials in Dravet syndrome and Lennox-Gastaut syndrome, and Takeda had already discontinued development in the latter condition. After meeting with the FDA about an indication for Dravet syndrome, a genetic form of epilepsy, regulators said current data “would not be capable of demonstrating substantial evidence of effectiveness,” Takeda said. The company added that soticlestat’s financial impact on full-year results is “expected to be immaterial.” Another Phase 3 program is also getting the boot. Takeda said it’s stopping work on the Exelixis-partnered drug Cabometyx in combination with Roche’s Tecentriq in metastatic castration-resistant prostate cancer. Cabometyx was originally developed by Exelixis, and then Takeda inked a deal for commercial and development rights in Japan in 2017. The drug is currently approved in the US for thyroid cancer, hepatocellular carcinoma and renal cell carcinoma. Takeda said the decision to pull the Cabometyx-Tecentriq combo in metastatic castration-resistant prostate cancer was “based on the trial results and assessment of Takeda’s development strategy.” A Phase 1 trial for TAK-500 in solid tumors was also closed “due to dose-limiting toxicities.” For the second consecutive quarter, Takeda raised its full-year revenue guidance. The company said in October that it expects full-year revenue to come in flat or slightly increase. It now expects an increase in revenue by a low single-digit percentage. The company also touted three Phase 3 readouts coming in 2025, including oveporexton in narcolepsy type 1, zasocitinib in psoriasis, and rusfertide for a rare blood disorder called polycythemia vera. “We are focused on advancing our promising late-stage pipeline and preparing for future launches. I couldn’t be more excited about what lies ahead for Takeda,” Weber said during an analyst call.