One-third of patients experienced an adverse event related to Stoke Therapeutics’ Dravet syndrome treatment during a midstage clinical trial, sending shares down 30%.
The readout, touted by Stoke as “positive new safety and efficacy data,” comes from several studies in pediatric patients with Dravet syndrome, a rare genetic form of epilepsy. The company’s first compound, an antisense oligonucleotide dubbed STK-001, is being evaluated in two phase 1/2a studies and an open-label extension study in children and adolescents with Dravet syndrome.
In March 2020, the FDA placed a partial hold on one of the trials called Monarch. This past spring, the FDA greenlit the administration of 70 mg single dose in the study, though multiple doses of STK-001 above 45 mg remain under the partial hold.
The biotech has now shared data on reductions in convulsive seizure frequency across three dose cohorts—30 mg, 45 mg and 70 mg—three and six months after dosing. At the highest dose, mean reduction in convulsive seizure frequency was 80% for six patients at three months after last dose, increasing to 89% for three patients at six months.
For 14 patients receiving the 45 mg dose, the mean reduction in convulsive seizure frequency was 19% at three months, jumping to 45% for the eight patients at six months.
This efficacy is lower than expected, given an interim readout last fall that found six patients receiving a 45 mg dose had 55% median seizure reductions. However, the change in measures (mean and median) make it difficult to accurately compare the efficacy changes.
“One of the things that has been really challenging for getting people to understand is—we are treating Dravet syndrome in a completely different way, so everything you learned before you have to forget,” Stoke CEO Edward Kaye, M.D., said on a July 25 investor call. “One of the things I think we've learned is—it takes time for this drug to work.”
Most patients in the study were already taking available anti-seizure medicines, making the reductions in seizures that Stoke observed quite meaningful, Joseph Sullivan, M.D., professor and director of the Pediatric Epilepsy Center of Excellence at the University of California-San Francisco, said in Stoke's July 25 release. He highlighted how STK-001 is designed to address the syndrome itself and not just the seizures, which would be the first therapy of its kind if approved.
Stoke said the therapy was "generally well-tolerated," however, 32% (24) of the 74 patients experienced an adverse event tied to the investigational treatment. The most commonly reported treatment-emergent adverse events were CSF protein elevations, vomiting and irritability. A fifth (20%) of all patients experienced a serious adverse event, though 14 of 15 of the events weren’t considered drug-related. There weren’t any study discontinuations related to STK-001.
Previously, one patient in a study called Admiral received multiple doses of STK-001 at 70 mg and experienced suspected unexpected serious adverse reactions related to the treatment. The patient completed the study and Stoke amended the trial’s protocol to let investigators decide whether to give two or three doses of 70 mgs before patients would be eligible to enroll in the extension trial.
Stoke's shares sunk 30% from $9.53 apiece at market close Monday to $6.70 this morning.
More data is expected in early 2024 after the phase 1/2a studies wrap. Stoke will then share an update on plans for a phase 3 trial.
Stoke is focused on addressing the underlying causes of severe diseases through the up regulation of protein expression using RNA-based medicines. STK-001 has snagged both orphan drug designation and rare pediatric disease designations from the FDA.
Editor's note: This article was updated at 3 p.m. ET on July 25 to include additional background information on the trials and comment from the investor call.