Stoke Therapeutics is gearing up for a pivotal trial of its lead program for a rare genetic epilepsy disease and announced positive results from its Phase I/IIa study in children with Dravet syndrome.
Courtesy of Stoke Therapeutics
Stoke Therapeutics is gearing up for a Phase III trial studying its lead candidate in children with Dravet syndrome after announcing positive results from a Phase I/IIa study Monday.
Stoke’s STK-001 targets the haploinsufficiency of the SCN1A gene and, if approved, could be the first therapeutic to address the root cause of Dravet syndrome.
The trials included children aged 2-18 who had already been treated with three or more anticonvulsant medications. The dataset is still small, as the trial works on a dose escalation of the drug. The six patients at the highest dose observed so far, 45 mg, had a 55% median reduction in convulsive seizure frequency.
The Phase I/IIa studies are ongoing to hone in on the therapeutic range for drug dosing that will be utilized in Phase III. More patients will be treated with the 45mg while an addition of 70mg dosing will be trialed. Additional data is anticipated in 2023 from these cohorts.
Stoke will move ahead into discussions with regulatory authorities and plans for a Phase III trial in 2024. This trial will include the same age group, with the potential for an additional study in younger patients. Most Dravet diagnoses occur before age one, but seizures are less frequent in those initial years, so establishing data for the trial is complicated.
Current treatments only address the symptom of seizures as patients are placed on one or more anticonvulsant medications to reduce the frequency. The goal of STK-001 is to bring a new, more effective option for treatment to the Dravet community.
“What we’re hoping to do is to really treat the entire disease and try to address not only the seizures but other aspects of the disease,” said Dr. Edward M. Kaye, CEO of Stoke, in an interview with BioSpace.
“That’s why we like the idea of trying to treat the genetic cause rather than simply treat the seizures. We’re hopeful that we’re going to have a much broader effect on this disease and all the symptoms these patients have.”
The company’s proprietary research platform, TANGO, applies to diseases where one copy of the gene functions normally, but the other does not. The team designs antisense oligonucleotides that bind to the pre-mRNA of the healthy gene and “stoke” protein production to compensate for the non-functioning copy.
Kaye is no stranger to rare disease drug development. In his six years at Sarepta Therapeutics, he drove the development of Exondys 51, the first drug approved by the FDA for Duchenne Muscular Dystrophy. The approval proved a bit controversial in 2017 but has been a big earner, delivering $122 million in net revenue this year for Sarepta in Q3 alone.
While STK-001 isn’t claiming to be a cure for Dravet syndrome, Kaye is hoping it will make a dramatic difference in the quality of life for patients and their families. Clinical studies are showing early signs of improvement in non-seizure comorbidities after long-term treatment.
The biotech is running open-label extensions to continue to assess these improvements. Kaye said the quality-of-life improvement will be “an important part of some of the discussions we have with regulatory authorities.”
Patients treated with the therapy so far are also not showing sedation or some of the other common anticonvulsant side effects, despite being on three or four different medications. Adding another drug to patients’ current regimens typically results in compounding side effects.
“In clinical practice, I had an opportunity to follow these children,” Kaye said, referring to his time as a pediatric neurologist.
“One of the most frustrating things was you would reach a point when there were absolutely no medicines anymore you could use. You ran out. Sometimes you’d go through 20 different medicines in a single patient, and there was nothing else that you can do.
“What we’re trying to do is provide hope for people who have run out of their therapeutic options and hope that we can provide some type of an alternative and give them an improvement in their life,” he continued.
If approved, Stoke plans to take the drug to market itself in the U.S. and Europe, with the potential for a partner in the Asia Pacific region.
The biotech is also moving ahead in a program for Rett syndrome with partner Acadia Pharmaceuticals.
