Ovid Therapeutics Inc. (NASDAQ:OVID), a biopharmaceutical company committed to developing medicines that transform the lives of people with rare neurological diseases, today announced plans to move ahead with a single pivotal Phase 3 trial of OV101 in pediatric patients with Angelman syndrome based on its End-of-Phase 2 Meeting with the U.S. Food and Drug Administration (FDA). If successful, the Phase 3 efficacy and safety trial called NEPTUNE is intended to support a New Drug Application (NDA) for OV101 in Angelman syndrome. OV101 is a novel delta (δ)-selective GABAA receptor agonist.
Angelman syndrome is a rare genetic disorder that is characterized by a heterogeneous constellation of symptoms, including disturbances in communication, sleep, motor function, and behavior, and for which there are no approved medicines or established treatment paradigms.
Based upon review and discussion of the Phase 2 STARS trial results, the clinical trial design, and the applicability of Clinical Global Impressions of Improvement (CGI-I) as a primary endpoint, the FDA and Ovid are in general agreement that the pivotal Phase 3 NEPTUNE clinical trial to be completed prior to an NDA submission, will include the following elements:
Single 12-week, two-arm, randomized, double-blind, placebo-controlled trial
Approximately 50-60 pediatric patients aged 4 to 12 years, diagnosed with Angelman syndrome randomized to either placebo or OV101
Primary endpoint of change in overall CGI-I score
CGI-I will be used as a single primary endpoint, mainly due to the rare nature of Angelman syndrome, the lack of treatment options, the nonexistence of assessment instruments specific to Angelman syndrome, the heterogeneity of the disorder, and the lack of sensitivity or appropriateness of other validated measures. Based on feedback from the FDA, Ovid will develop a framework for study investigators to ensure uniform use of the validated CGI-I scale by focusing on specific symptoms that are relevant and important to patients with Angelman syndrome and their caregivers.
Ovid expects to begin enrollment of the NEPTUNE trial in the second half of 2019, pending FDA concurrence on the study protocol and supporting framework and materials. Updates and further details of this trial, including secondary endpoints, will be provided upon trial initiation.
“It is important to acknowledge that while this meeting was a milestone for Ovid, and provides a clear path forward, it is an even more momentous one for the Angelman syndrome community,” said Jeremy Levin, DPhil, MB, BChir, chairman and chief executive officer of Ovid Therapeutics. “From the relationships we have formed within the community, to the completion of the first industry-sponsored trial in Angelman syndrome, we are very encouraged by the clinical progress we’ve made. With the thoughtful assistance and clear direction from the FDA, we now move forward to a pivotal trial that we hope will result in the first approved medicine for individuals living with this disorder.”
“The End-of-Phase 2 Meeting was productive and helped us understand the FDA’s expectations for a pivotal trial of OV101 in Angelman syndrome,” said Amit Rakhit, M.D., MBA, chief medical and portfolio management officer of Ovid Therapeutics. “As with many rare genetic disorders, symptoms of Angelman syndrome usually appear early in childhood, and persist and evolve into adulthood. We have completed juvenile toxicology studies which, in addition to our pharmacokinetic/pharmacodynamic (PK/PD) data, provide the basis for initiating a pivotal trial in younger patients. This trial is not only an important next step of our OV101 strategy, but also part of our overall mission to bring medicines to people who have no or limited treatment options.”
In addition to the planned Phase 3 NEPTUNE trial, Ovid is initiating the ELARA clinical trial, an open-label extension study for individuals with Angelman syndrome who have completed any prior OV101 study. ELARA will use once-daily dosing and will assess long term safety and tolerability in addition to efficacy measures. Trial initiation activities are underway. The Company is also exploring options for patients under four years of age.
Phase 2 STARS Trial Design and Results
STARS was a 12-week, double-blind, placebo-controlled Phase 2 trial which enrolled eighty-eight patients (adults, n=66; adolescents, n=22) 13 to 49 years of age diagnosed with Angelman syndrome. The study randomized patients to one of three arms: once-daily (QD) dose of OV101 at night (15 mg), twice-daily (BID) dose of OV101 (10 mg in the morning and 15 mg at night), and placebo.
The primary endpoint of the STARS trial was to assess the safety and tolerability of OV101 compared to placebo. The STARS trial also explored the clinical utility of OV101 on improvements in clinical global impressions, behavior, sleep, and gross and fine motor skills.
Comprehensive data from STARS were provided in a press release issued October 25, 2018.