Dive Brief:
- Stoke Therapeutics on Tuesday revealed study results from a pair of small, mid-stage trials testing a medicine designed to target the underlying cause of Dravet Syndrome, a rare form of genetic epilepsy.
- The results showed patients on the highest tested dose experienced a median of 42% fewer seizures through three months after treatment, versus 18% and 28% reductions for those on lower doses. The data were below analysts’ expectations and, for the middle dose, were worse that what Stoke reported last November.
- Stoke claims a different "point" analysis better captures its drug’s effects, which may deepen with time. It pointed to data showing that, at three months after the last treatment, those on the highest dose had a median of 80% fewer seizures. At six months, the median reduction was 89%, Stoke said.
Dive Insight:
Stoke has tried for several years to develop what CEO Ed Kaye describes as a “Spinraza for genetic epilepsy.”
The company was co-founded by the inventor of Spinraza, a Biogen medicine for the rare neuromuscular disease spinal muscular atrophy, or SMA. Stoke claims its technology — a way of making RNA-based medicines that increase production of key proteins — could lead to a similarly effective drug for Dravet. The condition typically starts in infancy, and is characterized by long-lasting and potentially fatal seizures as well as cognitive and behavioral changes.
Stoke faces a different challenge than Biogen did, though. There were no SMA medicines available when Spinraza came along, while there are now several that can rescue Dravet patients from seizures or forestall them from happening. Stoke seeks to prove its drug can both prevent seizures and slow cognitive decline.
However, so far in testing the company has had trouble establishing that higher doses are superior to lower ones on measures of seizure control. Notably, the benefit reported for what was previously the highest tested dose — a 45 milligram infusion — hasn’t held up as more patients have enrolled.
In a recent research note, Leerink Partners analyst Rudy Li wrote that investors wanted to see at least a 50% median reduction in seizure frequency from the 45 milligram dose in Tuesday’s update. Instead, that number was 18% through three months and 26% through six.
According to Kaye, Stoke initially thought it would take about one month for patients to start responding to treatment. The company now believes the drug’s effects take longer to kick in and get more powerful with time, said Kaye, who was previously CEO of Sarepta Therapeutics.
Future studies will therefore need to be longer, likely a year, to fully show the drug’s benefit, he said in an interview.
To support that argument, Stoke pointed to results from a newly tested, 70 milligram dose, and by comparing to baseline patients’ seizure rates at a specific time following treatment, rather than during and after treatment. There have also been signs in an extension study that the drug affects behavior and cognition over time.
“We're starting to see evidence that it's working as we had hoped it would be,” Kaye said.
The company intends to test its theory by giving patients a 70 milligram infusion as a loading dose, and 45 milligrams every four months afterwards, Kaye said.
But Stoke faces considerable skepticism. Shares lost more than one-third of their value Tuesday and, at less than $7 apiece, trade at their lowest levels since the company’s initial public offering in 2019.
Safety also remains a question. The most common side effects reported so far have been vomiting and irritability. The company is watching elevations of cerebrospinal fluid, or CSF, protein, which was observed in some treated patients and may compound with additional treatment. Kaye said this is a known effect of other approved therapies infused into the spine, and Stoke hasn’t seen any complications.
“We’ll continue to observe these patients and make sure that case,” he said.
On Tuesday, the company reported that one patient given multiple 70 milligram doses of Stoke’s drug experienced a “suspected unexpected serious adverse reaction” that a trial investigator attributed to treatment.
According to Kaye, the reaction was linked to Stoke’s drug because, after several months of investigation, no other cause could be found. The patient, who completed the study, experienced some changes in behavior as well as on a neurologic exam, Kaye said.
Stoke plans to report additional results next year.
Editor's note: This story has been updated to correct the name of Leerink Partners, which was previously known as SVB Securities.