Sage Therapeutics is terminating the development of its drug dalzanemdor in Parkinson’s disease after a mid-stage test ended in disappointment.
The Phase 2 PRECEDENT trial compared the drug with placebo in 86 Parkinson’s patients with mild cognitive impairment. It missed its primary endpoint, failing to show a statistically significant difference in the Wechsler Adult Intelligence Scale Fourth Edition-IV Coding Test score at 42 days versus placebo, according to a Wednesday release.
Barry GreeneDalzanemdor, previously known as SAGE-718, also missed on all secondary endpoints, and CEO Barry Greene said in an investor call that there was “no difference” compared with placebo.
While Sage is best known for its GABA receptor modulators, such as its approved postpartum depression drug Zurzuvae and an experimental program partnered with Biogen called SAGE-324, dalzanemdor is the company’s biggest bet to expand into a new class of therapies and new diseases. After Wednesday’s failure, the shares $SAGE were down roughly 20% on the day.
On a call with investors Wednesday, Wall Street analysts asked how the data might read through to other ongoing trials in Huntington’s and Alzheimer’s disease. Greene and medical chief Laura Gault repeatedly emphasized that the Parkinson’s data are “not necessarily predictive” of future results. The endpoints across the trials are also distinct, Gault added.
Laura Gault“Even though they’re both movement disorders, the relationship between cognition and the movement symptoms is very different,” Gault said.
Dalzanemdor is an NMDA receptor positive allosteric modulator. The idea behind the drug, according to Sage’s website, is to increase signaling between NMDA receptors to help stabilize neural networks in the brain.
In a Wednesday morning note to investors, Stifel analyst Paul Matteis wrote that the Parkinson’s efforts were considered the riskiest of dalzanemdor’s three disease areas. Given the disease biology and the drug’s mechanism of action, Parkinson’s “arguably had the most tenuous mechanistic rationale,” Matteis wrote.
The efforts in each neurodegenerative disease also “could be thought of as somewhat independent shots on goal, though in our opinion the biology around NMDA modulation in these indications is super complicated and also non-linear,” Matteis added.
Though the company is stopping further development in Parkinson’s, three Phase 2 readouts for dalzanemdor in Huntington’s disease and Alzheimer’s disease — where it previously showed early promise — are expected by the end of the year.
Topline data from a small Phase 2 in Huntington’s patients with cognitive impairment are expected before Oct. 1, while a larger Phase 2 in the same indication is set to read out before the end of Q4. As for Alzheimer’s, Phase 2 results in patients with mild cognitive impairment and dementia are also anticipated before the end of 2024.
Greene and Gault declined interview requests through a company spokesperson.