Phase 2 trial shows dalzanemdor’s safety, disease’s cognitive impact
SURVEYOR study finds significant differences between patients, healthy adults
Significant impairments in cognitive function are evident in people with Huntington’s disease relative to healthy adults, as assessed with a disease-specific battery of cognitive tests, top-line data from a Phase 2 clinical trial show, meeting its main goal.
The two-part trial, called SURVEYOR (NCT05358821), also evaluated the safety and exploratory efficacy of dalzanemdor, being developed by Sage Therapeutics to improve cognition, against a placebo in the patient group.
Results showed that the experimental therapy was generally well-tolerated and associated with positive signs in cognitive abilities and functional capacity relative to a placebo.
“While symptoms of cognitive impairment can precede motor symptoms by up to 15 years, it is a historically underrecognized aspect of HD [Huntington’s disease] and there are no approved treatments for cognitive impairment in HD,” Laura Gault, MD, PhD, chief medical officer of Sage Therapeutics, said in company press release.
SURVEYOR findings “highlight the extent of cognitive impairment associated with HD and enhance our collective understanding of this devastating disease … further [underscoring] the importance of developing treatments that can address this critical unmet need,” Gault said.
Patients’ cognitive abilities tested using HD-CAB battery of tests
According to Sage, SURVEYOR trial findings will be used to inform dalzanemdor’s ongoing clinical program, which includes a larger placebo-controlled Phase 2 trial called DIMENSION (NCT05107128).
Dalzanemdor, formerly known as SAGE-718, is an oral treatment designed to modulate NMDA receptors, which are proteins involved in communication between nerve cells in the brain. By increasing the sensitivity of these receptors, the treatment aims to improve cognition in people with certain neurological conditions.
Cognitive problems are one of the most troublesome symptoms of Huntington’s, but consistently measuring the extent of cognitive impairment in Huntington’s patients can be challenging.
To truly understand if treatments like dalzanemdor are effective, it’s necessary to have well-validated measures of cognition that can be used in cognitive testing.
As such, the Phase 2 SURVEYOR study’s main goal was to determine whether people with Huntington’s had lower scores than people without the disease on the Huntington’s Disease Cognitive Assessment Battery (HD-CAB), an assessment that combines six standardized cognitive tests.
In the trial, 40 Huntington’s patients took the HD-CAB, as did 29 people without cognitive problems and who either had no family history of Huntington’s or had been tested but did not carry a Huntington’s-causing mutation.
Results showed that the Huntington’s patients scored significantly worse on the test than healthy participants at trial’s start.
In the study’s second part, the patients were randomly assigned to take an oral capsule of either dalzanemdor or a placebo, once a day in the morning for about one month (28 days).
The trial’s secondary goal was to assess dalzanemdor’s safety, with exploratory goals measuring changes in patients’ cognitive function and ability to perform daily activities.
However, “the study was not designed or powered to demonstrate a statistically significant difference between dalzanemdor and placebo,” Sage stated in its release.
Dalzanemdor being tested in separate Phase 2 and Phase 3 clinical trials
Results from this second trial part showed that dalzanemdor was generally well-tolerated, with no new safety issues identified. Most adverse events were mild to moderate in severity, and none led to treatment discontinuation, the company reported. No further details were provided.
Sage said there was a “small numerical difference” in HD-CAB scores between patients on dalzanemdor and a placebo at the study’s end, and “positive signals” toward improvements in HD-CAB subscores and functional skills with the therapy.
Trial data will continue to be evaluated to inform further studies of dalzanemdor, the company added.
The ongoing Phase 2 DIMENSION study is testing dalzanemdor against a placebo, each taken daily for nearly three months, in up to 178 Huntington’s patients. Its main goal is to evaluate how the treatment affects HD-CAB scores, and trial results are expected later this year, according to Sage.
Patients who finish either SURVEYOR or DIMENSION can choose to enroll in a Phase 3 trial called PURVIEW (NCT05655520), which is assessing dalzanemdor’s long-term safety and exploratory efficacy in Huntington’s patients.
PURVIEW is currently enrolling an additional group of patients, ages 25-65, with less severe cognitive impairments than those in the Phase 2 trials at sites in the U.S. and Canada.
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