Longboard’s shares triple as epilepsy med halves seizure rates in early-stage trial

What do you get when you halve the number of seizures across a group of difficult epilepsy disorders in an early-stage trial? For Longboard Pharmaceuticals, you get a tripling of your share price.

The California biotech’s bexicaserin reduced seizures by 53.3% across a population of patients with developmental and epileptic encephalopathies (DEE), according to a Tuesday morning press release. The results come in well above the 20.8% seen in a placebo group.

The results sent Longboard’s shares skyrocketing nearly 200% as the markets opened for the first day of 2024. The company closed out 2023 at $6.03 and opened the new year at $18.10.

The phase 1b/2a PACIFIC study included 52 patients ages 12 to 65 years old with different seizure disorders, including Lennox-Gastaut syndrome and Dravet syndrome. Dosing began with a 15-day titration schedule and then continued with the highest-tolerated dose for a maintenance period of 60 days. The patients were allowed to stay on a regimen of up to four anti-seizure medications during the study.

Breaking down the results by disorder, bexicaserin led to a 72.1% mean reduction in Dravet-related seizures, 48.1% in Lennox-Gastaut and 61.2% in DEE other, Longboard said.

The early-stage results will provide a push off for the phase 3 program, although Longboard executives were mum on specific next plans.

There was a high rate of side effect-related events during the trial, with 35, or 81%, of the 43 patients reporting treatment-emergent adverse events (TEAEs), including 28, or 65%, that were deemed drug-related. Just nine led to discontinuation of treatment. This compared to eight TEAEs in the placebo group, three of which were deemed drug-related, and zero discontinuations.

Chief Medical Officer Randall Kaye, M.D., said on a Tuesday conference call (PDF) that the majority of these events—including somnolence, decreased appetite, constipation, diarrhea and others—occurred during the initial titration period. Once patients got past the first 15 days on the study drug, the incidents mostly subsided.

“It was striking, if you get patients into the titration period, move them through the titration period at a dose that they can tolerate, when they get into the maintenance period, they maintain it,” he said. “So an important concept that is intrinsically part of the current study design is to start low and go slow. Wait for participants to tolerate the medication and when they tolerate it, then they can go on to the next step.”

This is a key learning that Longboard will apply to the phase 3 program, he noted.

Kaye said that the use of other seizure medications in the trial provided a “real world experiment” to show incremental benefit with bexicaserin above and beyond the standard care.

Longboard previously conducted market research with neurologists and epileptologists who treat patients with existing seizure meds including UCB’s Fintepla and Jazz Pharmaceuticals’ Epidiolex, as well as patient caregivers or parents of children living with DEEs.

About 74% of doctors surveyed said they would prefer Longboard’s bexicaserin if it had a seizure reduction of around 40%, CEO Kevin Lind said on the call. Today’s results, of course, exceed that number. The research also looked at physician preference if the seizure reductions reached 50%, with 85% preferring bexicaserin over Fintepla or Epidiolex. Caregivers, meanwhile, preferred Longboard’s medicine to the other options by more than 85%.

There’s much more data to come from the PACIFIC study, as today’s readout was just topline results. Analysts peppered the executives with questions about different data points missing from the readout, with Kaye and Lind promising more at a future medical conference.

One key missing data point is the pediatric population, as the lower age group of 12 to 17 was added later in the study, according to Lind. The youngest patient was 12 years old, while the trial had a mean age of 23. But the fact that bexicaserin seemed to work in older patients—who had been on numerous other treatments and potentially had a high seizure burden—is notable, according to the executives.

“One of the concerns we had early on was, are we going to be able to demonstrate as significant of an effect in these older patients, where they've really been on a lot of medications and they've been on a very, very long journey,” Lind said. “So for us to demonstrate this level of effect, not in two-year-olds, not in three-year-olds—where I think the consensus would be that's a lot easier to demonstrate—we're really excited about how strong the effect we showed was.”