A company developing a drug for a rare neurological disorder that produced encouraging, but mixed results in a prior study has initiated its Phase III trial.

New York-based Ovid Therapeutics said Thursday that it had initiated the NEPTUNE study of OV101 in Angelman syndrome, a genetic disorder that causes developmental disabilities and problems with sleep, movement, balance and speech. The initiation followed what the company called productive discussions in a Type C meeting with the Food and Drug Administration.

Starting in the third quarter of this year, the study will enroll 60 patients aged 4 to 12, who will be randomized to receive a once-daily dose of either OV101 or placebo. As a primary endpoint, the trial will use the Clinical Global Impressions-Improvement (CGI-I) scale, which the company has renamed CGI-I-AS, “to reflect the fact that relevant anchors and training materials are specific to Angelman syndrome,” CEO Jeremy Levin said in a statement. “The use of CGI-I-AS as a sole primary endpoint is important. As was demonstrated in the Phase II STARS trial, the CGI-I scale is designed to detect change from baseline in each individual in a disorder with substantial clinical heterogeneity.”

The company released data from the STARS trial on Aug. 6, 2018, showing a highly statistically significant improvement in CGI-I after 12 weeks of treatment for OV101 compared with placebo. For patients who received the drug once daily at 15mg, the mean change in CGI-I score was 3.35 after six weeks and 3 after 12 weeks. Under the CGI-I scale, a lower score indicates a greater degree of improvement, with 3 meaning “minimally improved,” 2 meaning “much improved” and 1 meaning “very much improved.” A score of 4 indicates no change from baseline, and higher scores indicate the condition worsening.

When the STARS results for patients receiving 15mg once daily or 10mg and 15mg twice daily were pooled, 66.7 percent showed an improvement, compared with 39.3 of those on placebo. However, whereas the once-daily 15mg dose showed high statistical significance on improvement, the arm of patients receiving the higher dose missed statistical significance. In addition, the company stated that an analysis of domains of behavior, sleep and gait did not show a statistically significant difference from placebo.

Following the announcement of the STARS data, the company’s shares fell 40 percent, from $9.52 to $5.67 on the Nasdaq. Shares of the company were trading at $1.81 late Thursday morning following the news about the Phase III meeting, but were up slightly.

Ovid said it anticipates topline data from NEPTUNE in the middle of next year. OV101 is also being tested in a Phase II study among patients with fragile X syndrome, which is still enrolling and is expected to have results around the end of this year or early 2020. OV101 is a delta-selective GABA-A receptor agonist. Levin is also the chairman of the Biotechnology Innovation Organization for the 2019-2020 term.

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