Seizure frequency reduced as much as 85% in phase 1/2a studies of Dravet syndrome drug

Key takeaways:

• Participants given STK-001 in one dose experienced a 43% median seizure reduction at 3 months.
• Clinically meaningful improvements were reported from baseline to 12 months in cognition and behavior.

Seizure frequency was reduced as much as 85% at 3 months in young patients with Dravet syndrome treated with a proprietary antisense oligonucleotide, according to results of phase 1/2a studies released by the manufacturer.

In a press release, Stoke Therapeutics reported positive results from two open-label clinical trials and their respective open-label extension (OLE) studies of STK-001 to treat the rare condition in patients aged 2 to 18 years.

Analysis of 19 participants who were treated with one, two or three doses at 70 mg revealed substantial reductions in convulsive seizure frequency compared to baseline at both 3 and 6 months. Participants in the one-dose cohort experienced a 43% median reduction at 3 months and 57% at 6 months. Participants in the two- or three-dose cohort saw a median reduction of 85% and 74%, respectively.

A total of 68 of 74 eligible participants who completed treatment in the parent studies continued treatment in one of two OLEs, with 57 of 68 remaining for further treatment.

Among patients who received 30 mg or 45 mg of STK-001 in the parent studies who continued treatment every 4 months in the OLEs, data showed consistent and durable reductions in convulsive seizure frequency throughout the course of treatment. Clinically meaningful improvements were also reported from baseline to 12 months in multiple measures of cognition and behavior, including multiple sub-domains of the Vineland Adaptive Behavior Scale (VINELAND-3), per the release.

STK-001 was also generally well-tolerated, with 30% of participants experiencing a drug-related treatment-emergent adverse event (TEAE) and 22% reporting a serious TEAE, with all but one event unrelated to the study drug.

“The totality of these data provide compelling evidence that support the potential for STK-001 to be a disease-modifying medicine for patients with Dravet syndrome by treating the underlying cause of the disease, rather than just the symptoms,” Stoke CEO Edward M. Kaye, MD, said in the release.

Based on FDA clearance and data from the studies, Stoke said it plans to meet with regulatory agencies to discuss a pending registrational study that includes initial doses of 70 mg followed by continued dosing at 45 mg.