Stoke Therapeutics, Inc. announced new data from two open-label Phase 1/2a studies and two open-label extension (OLE) studies of children and adolescents ages 2 to 18 with Dravet syndrome who were treated with STK-001. Data from these studies showed clinically meaningful effects, including substantial and durable reductions in convulsive seizure frequency and improvements in multiple measures of cognition and behavior that support the potential for disease modification. These improvements were observed among a highly refractory group of patients who were already taking the best available anti-seizure medicines. STK-001 has been generally well-tolerated in studies to date. The Company also announced clearance from the U.S. Food and Drug Administration (FDA) that allows patients to receive three doses of 70mg followed by continued dosing at 45mg. Based on this regulatory update and these data, the Company plans to meet with regulatory agencies to discuss a registrational study that includes initial doses of 70mg followed by continued dosing at 45mg. The Phase 1/2a studies were multi-center and included children and adolescents who have an established diagnosis of Dravet syndrome. Patients enrolled in these studies were highly refractory to treatment and taking the best available anti-seizure medicines: 85% of patients were taking at least three and 54% were taking at least four medicines to control seizures. Half the patients in the studies were taking concomitant fenfluramine. New data from a combined analysis of 19 clinically evaluable patients who were treated with one, two or three doses of 70mg demonstrated substantial reductions in convulsive seizure frequency compared to baseline at 3 months and at 6 months after the last dose, one of several secondary endpoints in each study. Open Label Extension Studies: Durable reductions in seizures and clinically meaningful improvements in multiple measures of cognition and behavior over 12 months with continued dosing at 30mg and 45mg Eligible patients who completed treatment in the Phase 1/2a studies continued treatment with STK-001 in one of two OLEs. At the time of the analysis, 92% (68/74) of eligible patients had enrolled in the OLEs and 84% (57/68) remained in the studies. Durable reductions in convulsive seizure frequency were observed throughout the course of treatment. This analysis only included patients who received >30mg of STK-001 in the Phase 1/2a studies and then continued treatment with STK-001 (30mg or 45mg) every four months in the OLEs. Clinically meaningful improvements from baseline through 12 months were observed in multiple measures of cognition and behavior, including multiple sub-domains of the Vineland Adaptive Behavior Scale (VINELAND-3). These improvements are in stark contrast to recent natural history study data that showed that, on average, patients with Dravet syndrome experienced no meaningful improvement in convulsive seizure frequency and exhibited widening gaps in cognition and behavior compared to neurotypical peers, despite treatment with the best available anti-seizure medicines. Key Safety Findings:
At the time of the analyses, 81 patients had been treated with STK-001. Safety findings are summarized below. STK-001 was generally well-tolerated across the Phase 1/2a and OLE studies. In the Phase 1/2a studies: 30% (24/81) of patients experienced a treatment-emergent adverse event (TEAE) that was related to study drug. The most common were CSF protein elevations and procedural vomiting; and 22% (18/81) of patients had a treatment-emergent serious adverse event. These events were assessed as unrelated to study drug except for the previously reported case of one patient who experienced Suspected Unexpected Serious Adverse Reactions (SUSARs). A greater incidence of CSF protein elevation was observed in the OLEs. 74% (50/68) of patients in the OLEs had at least 1 CSF protein value >50 mg/dL. No clinical manifestations have been observed in these patients.
Across the studies, one patient discontinued treatment due to study drug. As previously reported, this patient discontinued treatment in the OLE due to elevated CSF protein.