Sage wilts as Huntington's prospect flunks trial

Sage Therapeutics' run of bad news has continued with a failed phase 2 trial of dalzanemdor as a treatment for cognitive impairment associated with Huntington's disease, spelling the end of the programme.

The Cambridge, Massachusetts-based biopharma said today that the DIMENSION study showed no significant difference between dalzanemdor and placebo on the change from baseline on the Symbol Digit Modalities Test (SDMT) at day 84, the primary endpoint, and also missed all its secondary endpoints.

"We are disappointed by the results of the DIMENSION Study, especially for the individuals and families affected by Huntington's disease who have long awaited new treatment options," said Barry Greene, Sage's chief executive.

In connection with the poor result, Sage has also opted to discontinue an ongoing open-label safety study of dalzanemdor in Huntington's called PURVIEW.

The demise of dalzanemdor comes after a torrid period for Sage that kicked off with a narrower-than-hoped FDA approval last year for Zurzuvae (zuranolone) in post-partum depression (PPD) but not the larger indication of major depressive disorder.

That was followed by failed trials of dalzanemdor in Alzheimer's and Parkinson's, the loss of Biogen as a partner for essential tremor candidate SAGE-324 after a lacklustre phase 2 readout, and a decision to give up on the development of zuranolone for MDD, which prompted a sweeping round of layoffs and a narrowing of its focus last month.

The cuts included a broad swathe of Sage's R&D workforce, reflecting a strategy of focusing on the commercialisation of Zurzuvae for PPD. Meanwhile, its only other approved therapy – older PPD option Zulresso (brexanolone) – has continued to see sales decline and will be discontinued at the end of this year.

Zurzuvae was once tipped as a potential blockbuster, but its limited label has pegged back sales growth, with sales by partner Biogen reaching $22 million in the third quarter, generating $11 million for Sage in collaboration revenue.

Shares in the company continued a precipitous decline since the start of the year, falling more than 4% in premarket trading to $4.91. The stock is down nearly 80% over that period, with Sage's valuation falling to around $300 million from upwards of $1.2 billion.

With dalzanemdor now consigned to the scrap heap, speculation has begun over Sage's future direction, now that its pipeline is limited to a speculative series of early-stage programmes including candidates targeting NMDA and GABA neurotransmitters for indications including epilepsy and neurodevelopmental disorders.

The company is, however, still fairly well financed – with cash reserves of $569 million as of 30th September – which could raise the possibility of a merger to expand its R&D portfolio.

Photo by Brittany Colette on Unsplash