Marinus Pharmaceuticals reported Monday that its IV drug met only one of two key endpoints in a Phase 3 study for prolonged seizures.
In the Phase 3 RAISE study, 96 patients with refractory status epilepticus (RSE) — prolonged seizures that don’t respond to two previous antiseizure medications — were given either an IV formulation of Marinus’ treatment ganaxolone or placebo on top of standard care. Marinus markets an oral suspension of ganaxolone as Ztalmy.
Eighty percent of patients saw their seizure cease within 30 minutes of beginning IV ganaxolone compared to 13% of placebo patients — meaning the study met its first co-primary endpoint.
However, the trial failed to hit its second co-primary endpoint. In the study, 63% of patients did not progress to IV anesthesia for 36 hours following initiation of IV ganaxolone, compared to 51% of patients who received placebo. The difference in the two arms was not statistically significant, with a p-value of 0.162.
A study with two co-primary endpoints typically has to hit both to be considered successful.
Efficacy questions were initially raised in April, when the company had announced that the study was continuing past an interim analysis.
Marinus said in a press statement that it plans to discuss a “potential path forward for IV ganaxolone” with the FDA in refractory status seizures.
“Phase III data of IV ganaxolone in RSE life-threatening seizures confirms our view the study failure was due to a high placebo response (rather than a lack of drug activity). [Marinus] will meet with the FDA to determine a path forward, and the most likely scenario would be to run another study,” Jefferies analyst Andrew Tsai wrote in an investor note Monday morning.
Joseph HulihanIn a press statement, Marinus’ chief medical officer Joseph Hulihan pointed to factors that could impact the study outcomes, including that several baseline characteristics between the two study arms were not balanced. Duke University Medical Center neurologist Aatif Husain, who’s on Marinus’ scientific advisory board, said in the statement that future studies should consider using “objective measures such as EEG” instead of endpoints “dependent on a proxy measure such as use of IV anesthesia.”
While IV anesthesia is used to treat uncontrolled seizures after patients have failed previous medications, Tsai noted that its use “could be due to several factors, such as a rebound in status or RSE patients having other underlying medical issues (e.g. respiratory depression) – so variability can occur within 36 hours.”
Marinus also noted that hypotension was more common in the treatment arm, but overall incidence of adverse events was similar between the study arms.
The company said full data will be shared at an upcoming medical meeting.