Shares of a company developing a drug to treat depression dropped sharply Thursday following the announcement that its registration-directed clinical trial had missed its primary endpoint.
Cambridge, Massachusetts-based Sage Therapeutics said Thursday that topline results of its Phase III MOUNTAIN study of SAGE-217 in major depressive disorder (MDD) showed it did not meet the goal of showing a statistically significant reduction in total score on the 17-item Hamilton Rating Scale for Depression, or HAM-D, at 15 days of treatment, compared with placebo.
Shares of the company were down more than 59% in afternoon trading on the Nasdaq following the news.
But on a conference call with investment bank analysts, Sage executives insisted that the trial was not a complete bust.
“We view this study – it’s certainly our view and has to be confirmed – as strongly supportive of a generalized MDD filing,” CEO Jeff Jonas said, emphasizing that the study had not failed.
The company said that SAGE-217, administered at 30mg, was associated with a 12.6-point reduction in HAM-D, compared with 11.2 points for placebo, with a p-value of 0.115. However, patients receiving the drug did achieve statistically significant reductions in HAM-D at days 3, 8 and 12, with a p-value of no more than 0.018 for each time point. In statistics, a p-value of 0.05 or less indicates statistical significance.
But a post-hoc analysis also indicated that 9% of patients in the treatment arm had no measurable drug concentration, which would be consistent with their not having taken the drug in compliance with protocol. When those patients were excluded, the primary endpoint reached statistical significance at day 15.
“The one takeaway from this study, to be blunt: If you don’t take the drug, it’s not going to work,” Jonas said on the call.
In addition, the study enrolled more patients than prior studies of the drug with an overall distribution of milder severity of symptoms. When only counting the 124 patients with a HAM-D score of 24 or higher, the results reached statistical significance at all timepoints, including at day 15.
Data showed the drug to be generally well-tolerated, with overall reports of side effects being similar between the two study arms during the 14-day treatment period and the 28-day follow-up.
“This study did not meet the primary endpoint. With that, the data are supportive of the activity of SAGE-217 in MDD given the statistical significance at the majority of timepoints, and in relevant populations,” Jonas said in a statement. “Notwithstanding the finding on the primary endpoint, the drug displays good activity on most measures.”
Photo: Creative_Touch, Getty Images
