Sage Therapeutics has seen another clinical trial go up in smoke. The biotech called time on its plans to develop dalzanemdor in Alzheimer’s disease after seeing midphase data, adding to an earlier Parkinson’s flop and leaving the team looking to an upcoming readout in Huntington’s to rescue the prospect.
The failed study compared the NMDA receptor positive allosteric modulator dalzanemdor, also known as SAGE-718, to placebo in 174 people. Sage designed the trial to show if the drug candidate can treat mild cognitive impairment and mild dementia in Alzheimer’s. The biotech now has its answer—and it was bad enough to extinguish plans to keep studying dalzanemdor in the indication.
Dalzanemdor was no better than placebo on the primary endpoint, which used the WAIS-IV Coding Test to assess executive function. The test is similar to the measures where dalzanemdor looked the most promising in Sage’s open-label study but the biotech failed to replicate the earlier signs of efficacy.
The impact of the primary endpoint failure was drilled home by the absence of meaningful differences between the dalzanemdor and placebo cohorts on exploratory endpoints, including the RBANS measure of cognitive impairment and the MoCA assessment of mild cognitive dysfunction. Lacking silver linings to offset the primary endpoint flop, Sage has dropped plans for further development in Alzheimer’s.
The one positive is a lack of safety red flags that could sink Sage’s pursuit of other indications. Sage said dalzanemdor was generally well tolerated and no new safety signals were found, leaving it free to keep studying the molecule in Huntington’s.
Sage is aiming to publish topline data from a phase 2 trial in Huntington’s this year. The DIMENSION trial is evaluating the effect of dalzanemdor on cognitive function using Symbol Digit Modalities Test (SDMT). Informed by the findings of a small trial, Sage instigated a mid-study switch to make SDMT the primary endpoint of DIMENSION earlier this year.
Speaking on an earnings call in July, Laura Gault, chief medical officer at Sage, said SDMT has a similar design to the WAIS-IV coding test used in the Alzheimer’s study. The failed Parkinson’s trial also used WAIS-IV as its primary endpoint. One reason to think dalzanemdor may fare better in the next readout is Huntington’s is a more homogenous patient population than Alzheimer’s or Parkinson’s.
Sage’s share price fell 11% to $6 in premarket trading.