Sage Therapeutics’ dalzanemdor has flamed out, recording its third midphase flop in seven months. The hat trick of failures drove Sage to drop plans for further development of the NMDA receptor positive allosteric modulator.
Massachusetts-based Sage threw in the towel after seeing data from a phase 2 trial that compared the drug candidate to placebo in 189 people with cognitive impairment associated with Huntington’s disease. After 12 weeks, scores on a measure of cognitive function were not significantly better in the dalzanemdor cohort than in the placebo arm, causing the trial to miss its primary endpoint.
The secondary endpoints failed to salvage the study. Sage reported no statistically significant or clinically meaningful differences between the treatment and control cohorts on a range of measures that looked at visual attention, task switching, experiences in daily life and more.
The bright spot was the lack of new safety signals, but that was scant consolation for a program that has comprehensively flopped this year.
Going into 2024, Sage flagged a series of trial readouts on dalzanemdor in Alzheimer’s, Huntington’s and Parkinson’s diseases as key events. An early warning that Sage may be heading for an annus horribilis emerged in April, when the biotech reported the failure of dalzanemdor in Parkinson’s. The biotech forged ahead to the next readouts, noting differences between the indications to keep spirits up despite the setback.
Alzheimer’s and Huntington’s patients do have different symptoms and disease biology, but that made no difference to the headline outcomes. Dalzanemdor flunked a phase 2 trial in Alzheimer’s last month and completed the clean sweep of flops when news of the Huntington’s failure crossed the wires Wednesday.
The succession of failures has blown a hole in Sage’s pipeline. The biotech regained control of SAGE-324 from Biogen but only after the failure of an essential tremor trial raised doubts about its future. Sage is also working on early-stage assets, such as the GABAA receptor modulator SAGE-319, but dalzanemdor was its hope for a near-term success.
In mid-October, Sage said it would lay off about 165 workers, including more than half its R&D team, in an effort to "right-size Sage for future growth potential," CEO Barry Greene said in a statement at the time. Then, later in the month, the company disclosed a plan to discontinue its older postpartum depression drug Zulresso as it focuses on the newer FDA-approved option Zurzuvae.
Shares in Sage fell 8% to around $4.50 in premarket trading Wednesday. Sage traded above $25 a share in January, but the series of dalzanemdor setbacks has contributed to the steady decline of the stock since then.