Marinus Pharma (MRNS) Announces Top-line Results from Phase 2 Study of Ganaxolone in PCDH19 Pediatric Epilepsy

September 29, 2016 9:04 AM EDT
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Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a biopharmaceutical company dedicated to the development of innovative therapeutics to treat epilepsy and neuropsychiatric disorders, today announced top-line results from a Phase 2 exploratory open-label clinical trial evaluating ganaxolone, its CNS-selective GABAA modulator, in females with PCDH19 pediatric epilepsy. In the trial, ganaxolone reduced seizure frequency from baseline in the majority of patients enrolled in the study and was generally safe and well tolerated. PCDH19 pediatric epilepsy is a rare, serious epilepsy characterized by early-onset cluster seizures, cognitive and sensory impairment, and behavioral disturbances, with no approved treatments. In 2015, the U.S. Food and Drug Administration granted Orphan Drug Designation to ganaxolone for the treatment of PCDH19.

Top-Line Results:

  • 64% (7 of 11) of patients showed a seizure reduction compared to baseline.
    • 57% (4 of the 7 patients) showed a reduction of greater than 50% compared to baseline.
  • 73% (8 of 11) of patients showed an increase in seizure-free days.
  • 73% (8 of 11) of patients showed CGI-I (Clinical Global Impression of Improvement) scores of very much improved, much improved or minimally improved at their last visit when administered by the parent/caregiver, which correlated with overall seizure reduction and participation in the study extension.
  • Consistent with earlier studies, ganaxolone was generally safe and well tolerated. The most common drug-related adverse event was somnolence.

Michael G. Chez, M.D., a pediatric neurologist at Sutter Medical Center in Sacramento, California, and an investigator in the Phase 2 trial, commented, “The benefit that ganaxolone provided in reducing seizures is clinically meaningful for these difficult-to-treat patients with a severe, rare epilepsy. Children with PCDH19 epilepsy are faced with many comorbidities that impact the quality of life for them and their families. In addition to seizure reduction, the patients that I treated with ganaxolone displayed improved behavior and cognitive skills during treatment. A drug that can lessen seizure burden and behavioral comorbidities caused by this disease would be welcomed by patients, their families and the medical community.”

The open-label Phase 2 exploratory study enrolled 11 female children between 4 and 15 years of age at seven sites in the United States and one site in Italy. Enrolled patients had a confirmed PCDH19 genetic mutation and uncontrolled seizures despite antiepileptic pharmacotherapy. Ganaxolone was studied as an adjunctive treatment, administered as either oral liquid suspension or capsules, for 26 weeks after establishing up to 12 weeks of baseline seizure frequency. The primary efficacy measure was the percent change in seizure frequency per 28 days relative to the baseline. Secondary measures included percent increase in seizure free days from baseline and evaluation of the safety and tolerability of ganaxolone as adjunctive therapy.

The following table summarizes selected key efficacy measures for each patient:

Patient% Reduction in Seizure Frequency from Baseline% Increase in Seizure Free Days from Baseline
1 100.0% 22.5%
2 72.8% 852.8%
3 69.5% 31.6%
4 53.8% 4.9%
5 26.6% 27.4%
6 18.7% 7.5%
7 2.6% 32.2%
8 (3.5%) 9.2%
9 (140%) (2.9%)
10 (256%) (9.7%)
11 (1031%)* (89.5%)

*Seizure calendar data not verified with caregiver

A majority of patients experienced reduced seizures during ganaxolone treatment and elected to enter the study extension following completion of 26-weeks of ganaxolone treatment. All patients that experienced reduced seizures also experienced an increased number of seizure-free days. Ganaxolone was generally safe and well tolerated with somnolence (4/11), headache (3/11), seizure (3/11) and fatigue (3/11) reported as the most common drug related adverse events. Three adverse events were reported as serious (one patient with rash and two patients with seizures). Of the five patients who discontinued the study, two patients discontinued due to lack of efficacy and three due to an adverse event. Further data will be presented in future publications and medical meetings.

Albena Patroneva, M.D., Chief Medical Officer of Marinus Pharmaceuticals, commented, “I am excited by the positive signal seen in this first proof-of-concept clinical study in females with the rare genetic mutation of PCDH19. This clinical trial confirms that the PCDH19 mutation affects every child differently with respect to severity and frequency of seizures and comorbidities. The knowledge gained from this study will be invaluable in informing our overarching pediatric plan for ganaxolone. We are now enrolling patients with other pediatric genetic epilepsies who we believe are underserved by current approved therapeutic options and who may benefit from ganaxolone treatment.”

Marinus has expanded enrollment in this clinical trial to include patients with CDKL5, Lennox-Gastaut Syndrome and other pediatric genetic epilepsies. Data from these additional patient populations will be available in 2017 and, along with interactions with regulatory agencies, will inform the Company’s future pediatric orphan clinical development strategy.

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