RARE Daily

Stoke Surges After Reporting Positive Results from Dravet Syndrome Study

March 27, 2024

Rare Daily Staff

Stoke Therapeutics’ shares surged 90 percent after the company reported positive new data from two open-label phase 1/2a studies and two open-label extension 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.

Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged, and refractory seizures, beginning within the first year of life. Dravet syndrome is difficult to treat and has a poor long-term prognosis. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. The effects of the disease go beyond seizures and often include intellectual disability, developmental delays, movement and balance issues, language and speech disturbances, growth defects, sleep abnormalities, disruptions of the autonomic nervous system and mood disorders. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. There are no approved disease-modifying therapies for people living with Dravet syndrome. One out of 16,000 babies are born with Dravet syndrome, which is not concentrated in a particular geographic area or ethnic group.

STK-001 is an investigational new medicine for the treatment of Dravet syndrome currently being evaluated in ongoing clinical trials. Stoke believes that STK-001, a proprietary antisense oligonucleotide, has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. STK-001 is designed to upregulate NaV1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological NaV1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure comorbidities. STK-001 has been granted orphan drug designation by the FDA and the EMA, and rare pediatric disease designation by the FDA as a potential new treatment for Dravet syndrome.

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 up to four anti-seizure 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 of STK-001 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.

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 open label extension (OLE) studies. 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). STK-001 was generally well-tolerated across the Phase 1/2a and OLE studies.

Stoke said the U.S. Food and Drug Administration has cleared its request to allow 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 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,” said Edward Kaye, CEO of Stoke Therapeutics. “STK-001 is the first medicine in development to demonstrate substantial and durable reductions in seizure frequency and improvements in multiple measures of cognition and behavior. These effects were observed in patients who were already taking the best available anti-seizure medicines, which confirms our highly differentiated mechanism of action and approach to treating this disease.”

Photo: Edward Kaye, CEO of Stoke Therapeutics

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