Sage takes another hit as Alzheimer's drug is canned

Sage Therapeutics has said it will stop the development of dalzanemdor in Alzheimer's disease, a few months after pulling the plug on the drug in Parkinson's disease.

The decision, prompted by a phase 2 trial readout, leaves Sage with one final shot on goal for the programme in Huntington's disease when the results of the mid-stage DIMENSION trial emerge, likely later this year.

Dalzanemdor (formerly SAGE-718) is an oral positive allosteric modulator (PAM) of the glutamate NMDA receptor that is being tested for its ability to counteract mild cognitive impairment (MCI) in neurodegenerative disorders.

News of the outcome of the 12-week LIGHTWAVE study, which included 174 patients with MCI or mild dementia due to Alzheimer's, added to the pressure on Sage's share price, which has fallen around 71% since the start of the year on the back of a string of pipeline setbacks. The stock is trading around the $6 mark, having traded as high as $50 in the middle of last year.

Dalzanemdor was unable to show a statistically significant difference from baseline versus placebo on the WAIS-IV Coding Test score at Day 84, the primary outcome measure in LIGHTWAVE. That was accompanied by no significant differences between the two groups on secondary endpoints, including the RBANS measure of cognitive impairment and the MoCA assessment of mild cognitive dysfunction.

Analysts had been sceptical about dalzanemdor's chances of showing a benefit in the study after the failure of the PRECEDENT trial in Parkinson's, a view that was acknowledged by Sage Therapeutics' chief executive, Barry Green, who noted that Alzheimer's is "an incredibly complex and devastating condition."

Last month, Sage reported that Biogen had ducked out of a collaboration on a drug codenamed SAGE-324 for essential tremor, a debilitating neurological disorder that causes involuntary and rhythmic shaking, a few weeks after another disappointing phase 2 readout.

Last year, there was further disappointment for the company after another drug partnered with Biogen, Zurzuvae (zuranolone), was approved by the FDA for postpartum depression (PPD), but turned down for the much larger indication of major depressive disorder (MDD). The drug made sales of $27 million in the first half of the year, following a US launch last December.

"While we are disappointed by the results of the LIGHTWAVE Study, we are grateful to participants, investigators, care partners, patient advocates, and the Alzheimer's community, who helped make this important research possible," said Greene.

"We hope our work and these findings help to inform future research."

Photo by Steve Johnson on Unsplash