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June 13, 2016

Marinus Epilepsy Candidate Ganaxolone Fails Phase III Trial

  • Marinus Pharmaceuticals said today that it will end its clinical program to develop its lead product candidate ganaxolone in adult focal-onset seizures after the epilepsy treatment failed a Phase III trial.

    Instead, the company added, it will focus its ganaxolone development efforts on advancing the candidate in status epilepticus and pediatric orphan indications.

    Ganaxolone missed its primary endpoint of demonstrating a statistically significant difference from placebo in adults with drug-resistant focal-onset seizures, Marinus acknowledged.

    Ganaxolone missed the trial’s primary endpoint of percent change in the 28-day seizure frequency from baseline, with a median percent reduction of focal-onset seizures in the ganaxolone treatment arm of 21.28%, compared to 10.25% with placebo during the titration and 12-week treatment period.

    “We are disappointed with the outcome of this study, and the unfortunate impact on the epilepsy community and particularly the patients suffering from drug-resistant focal-onset seizures who are benefiting from ganaxolone treatment,” Marinus CEO Christopher M. Cashman said in a statement.

    Investors responded to the news by selling off shares of the company’s stock, whose share price in morning trading plunged 67% as of 10:15 am, to $1.75 from a close of $5.34 on Friday.

    The Phase III multinational, double-blind, randomized, placebo-controlled study was conducted at 61 sites in the U.S., Germany, Poland, Australia, Bulgaria, and Russia.  The study randomized 359 patients into two arms—179 patients to ganaxolone 1800 mg/day and 180 to placebo.

    The mean age of the study population was 41, with 63% of the participants being female, Marinus said. Of the patient population, 76% were receiving two or more concomitant available antiepileptic drugs, while 12% had been treated with a vagus nerve stimulator.

    Ganaxolone is a central nervous system (CNS)-selective gamma-aminobutyric acid A (GABAA) modulator being developed in three different dose forms—intravenous, capsule, and liquid—and intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Ganaxolone has been studied in more than 1300 subjects, both pediatric and adult, at therapeutically relevant dose levels and treatment regimens for up to 2 years.

    In these studies, Marinus said, ganaxolone was generally safe and well tolerated, with the most commonly reported adverse events of somnolence, dizziness, and fatigue.

    “We remain confident in the safety profile of ganaxolone and its ability to effectively reduce seizures in targeted patient populations,” Cashman added. “We are committed to building our ganaxolone franchise and are confident in the potential of ganaxolone in the treatment of status epilepticus and pediatric orphan seizure and behavior disorders. We will provide an update in the upcoming weeks on our clinical programs in these indications.”

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