Takeda's soticlestan fails key goal in two epilepsy trials

Takeda Pharmaceutical's experimental drug, soticlestat, recently underwent rigorous testing in two late-stage clinical trials to evaluate its efficacy in treating Dravet syndrome and Lennox-Gastaut syndrome. Despite high hopes, the trials did not achieve their primary endpoints. However, the company highlighted some encouraging aspects, suggesting that the drug's potential may still be worth exploring.

Sarah Sheikh, head of global development at Takeda, acknowledged the mixed results but emphasized the positive aspects. “While we would have wished for more definitive outcomes on the primary endpoints, we are encouraged by positive outcomes seen in the totality of the data and are looking forward to engaging health authorities to determine the best path forward," Sheikh stated.

The SKYLINE study focused on 144 pediatric and young adult patients suffering from refractory Dravet syndrome, a severe form of epilepsy. Meanwhile, the SKYWAY trial included 270 pediatric and adult patients with Lennox-Gastaut syndrome, another challenging epilepsy variant. Participants in both studies were randomly assigned to receive either soticlestat or a placebo, administered twice daily over a 16-week period, in addition to their existing antiseizure medications.

The primary objective of the SKYLINE study was to observe the percent change from baseline in convulsive seizure frequency over a 28-day period. Similarly, the SKYWAY trial aimed to measure the percent change from baseline in major motor drop (MMD) seizure frequency over the same timeframe. The top-line results showed that soticlestat narrowly missed achieving the primary endpoint in the SKYLINE study, with a p-value of 0.06. Despite this, Takeda reported that the drug achieved clinically meaningful and nominally significant results in several secondary measures, such as responder rate and scales for seizure intensity and duration.

Takeda did not disclose how soticlestat performed on secondary endpoints in the SKYWAY trial. However, the pharmaceutical company indicated that soticlestat, also identified as TAK-935, was generally well tolerated across both studies. This safety profile is crucial for potential future use of the drug in treating these severe epileptic syndromes.

The financial implications of these trial results are yet to be fully assessed. Takeda mentioned that they would evaluate the financial impact, including any potential impairment loss for intangible assets. This consideration follows the nearly $200 million Takeda paid in 2021 to regain full rights to soticlestat from Ovid Therapeutics.

In summary, while soticlestat did not meet its primary endpoints in these late-stage trials, the drug demonstrated some promising secondary outcomes. Takeda remains optimistic and plans to engage with health authorities to determine the most appropriate path forward. The pharmaceutical company balances cautious optimism with a commitment to thoroughly evaluating both the financial and clinical implications of the trial outcomes.