Marinus Pharmaceuticals announces results from two ganaxolone studies

Marinus Pharmaceuticals announced “positive” results from its Phase 2 clinical trials evaluating ganaxolone intravenous, or IV, and oral in women with postpartum depression, or PPD. Based on these results, the company is advancing both studies into the next phase of development to evaluate IV and oral dose regimens. There was a clear dose response relationship seen for three groups of patients receiving ganaxolone IV at median doses of 60, 90 and 140 microg/kg/h.The 140 microg/kg/h dose group demonstrated the most robust results, with a clinically meaningful 5.6-point reduction in Hamilton Rating Scale for Depression, or HAM-D17, compared to placebo at 48 hours that was durable through the last visit, day 34. These patients had a mean HAM-D17 reduction of 16.9 and 15.7 points from baseline at 60 hours and day 34, respectively. Overall, 75% of patients were responders, as defined as having a 50% reduction from baseline, at day 34 and 67% were responders at 60 hours. Additionally, 50% of patients achieved remission from depression, as determined by a HAM-D17 of 7, at day 34 and 33% achieved remission at 60 hours. Ganaxolone was safe and well-tolerated in all dose groups. Consistent with previous ganaxolone studies, the most common reported adverse events were sedation and dizziness. There were no serious adverse events reported, no discontinuations due to a treatment related adverse event and consistent with prior studies, there were no reports of syncope or loss of consciousness. The Clinical Global Impression of Improvement, or CGI-I, as well as the Edinburgh Postnatal Depression Survey, or EPDS, and Spielberger State-Trait Anxiety 6, or STAI-6, showed highly similar trends that were consistent with HAM-D17. Overall, 58 patients with PPD were randomized on a 1:1 basis to receive one of three ascending fixed IV 60-hour dose regimens of ganaxolone or placebo. No initial up titration was required and patients were down titrated over the final 12 hours of the 60-hour infusion. A bolus injection of ganaxolone prior to the 60-hour infusion was explored to test the safety and tolerability of a very short, high dose infusion. None of the dose groups were powered to generate statistical significance. Patients with a HAM-D17 score of 26 were considered for enrollment in the study. HAM-D17 measurements were conducted by a centralized rater and taken at various timepoints spanning from baseline to day 34. Enrollment is ongoing in the company’s oral study, a Phase 2 clinical trial to evaluate the safety, tolerability and efficacy of oral ganaxolone in women with PPD. Patients with a HAM-D17 score of 20 but less than 26 are being considered for enrollment in the study. Cohorts of patients enrolled in the initial open label phase of the study receive ascending dose regimens with oral ganaxolone. The efficacy endpoint is change from baseline in the HAM-D17 score. Patients in the most recent dose cohort who took oral ganaxolone for four weeks had a mean HAM-D17 reduction of 13.2 points 28 days from a baseline of 24.7 and a reduction of 15.7 points at day 36. This cohort is on-going and not all patients have reached day 28. As with IV, oral ganaxolone was generally safe and well-tolerated with no serious adverse events reported and no discontinuations due to treatment related adverse events. The company is advancing both the Magnolia and Amaryllis studies with data expected in the first half of 2019. The second part of the Magnolia Study will evaluate a short IV infusion followed by oral ganaxolone administration and the Amaryllis study will continue to optimize oral ganaxolone dosing.

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