NMDA receptor

The latest round of layoffs will see Sage reduce 33% of its total workforce. Credits: Wirestock Creators/Shutterstock.com After a series of mid-stage clinical trial failures, Sage Therapeutics has announced that it will jettison 165 employees, which totals 55% of its R&D team and 33% of its entire workforce. As per the 17 October press release, the move was made in a bid to strengthen the company’s financial and long-term operational positions while having the flexibility to tackle its immediate priorities. The restructuring, which is expected to be largely complete by the year’s end, is anticipated to incur a cost of $26–28m in Q4 2024. The reorganisation is also intended to allocate available resources towards continuing to support the commercial launch of Zurzuvae (zuranolone), a neuroactive steroid (NAS) gamma-aminobutyric acid type A (GABA-A) receptor-positive allosteric modulator designed to regulate mood and behavior. The small molecule therapy, jointly developed by Sage and Biogen , became the first US Food and Drug Administration (FDA)-approved oral treatment for postpartum depression in August 2023. Since its commercial launch in December 2023, Zurzuvae generated $6.2m and $7.4m in Q1 and Q2 2024, respectively. According to GlobalData’s consensus forecasts, Zurzuvae is expected to generate total sales of $607m in 2030. GlobalData is the parent company of Pharmaceutical Technology . Zurzuvae was also previously studied in major depressive disorder (MDD). However, along with its approval in postpartum depression, the FDA issued a complete response letter (CRL) stating that the drug did not demonstrate substantial evidence of effectiveness in MDD and that further studies were needed. Following the FDA’s rejection of Zurzuvae in MDD, Sage slashed its workforce by 40% to refocus its business priorities. See Also: FDA approves AbbVie’s VYALEV for advanced Parkinson’s treatment Glaukos eyes FDA approval for ocular therapy after Phase III win Sage has navigated choppy waters of late. Earlier this month, the company announced that its positive allosteric modulator of the NMDA receptor dalzanemdor failed to demonstrate superiority to placebo in the Phase II LIGHTWAVE (NCT05619692) study. The study evaluated the effects of dalzanemdor on cognitive performance in participants with Alzheimer’s disease. Based on data from LIGHTWAVE, Sage has decided to discontinue the development of dalzanemdor in Alzheimer’s. The Alzheimer’s trial news means that dalzanemdor has had two successive clinical failures. The candidate was also previously evaluated for the treatment of Parkinson’s disease. However, after failing the Phase II PRECEDENT study (NCT05318937), Sage pulled the plug on development in this indication. The biopharma’s remaining hopes for dalzanemdor rest on data from its Phase II DIMENSION study (NCT05107128) for the treatment of Huntington’s disease. Data from this study is expected by late 2024.

– In the Phase 2 LIGHTWAVE Study, dalzanemdor (SAGE-718) did not demonstrate a statistically significant difference from baseline in participants treated with dalzanemdor versus placebo on the primary endpoint – Dalzanemdor was generally well-tolerated and no new safety signals were observed – Topline data from the Phase 2 DIMENSION Study of dalzanemdor in Huntington’s Disease expected later this year CAMBRIDGE, MA, USA I October 08, 2024 I Sage Therapeutics, Inc. (Nasdaq: SAGE) announced today topline results from LIGHTWAVE, a 12-week, Phase 2 randomized, double-blind, placebo-controlled study to evaluate the effects of dalzanemdor (SAGE-718) in participants with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s Disease (AD). The LIGHTWAVE Study did not demonstrate a statistically significant difference from baseline in participants treated with dalzanemdor versus placebo on the Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Test score at Day 84, the primary outcome measure of the study. Based on these data, the Company does not plan further clinical development of dalzanemdor in AD. The Company expects to report topline data from the Phase 2 DIMENSION Study of dalzanemdor in people with cognitive impairment associated with Huntington’s Disease later this year. “Alzheimer’s Disease is an incredibly complex and devastating condition, and people with related mild cognitive impairment and mild dementia need more treatment options. 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. We hope our work and these findings help to inform future research,” said Barry Greene, Chief Executive Officer, Sage Therapeutics. LIGHTWAVE Study Results The LIGHTWAVE study was a 12-week, Phase 2 randomized, double-blind, placebo-controlled study to evaluate the effects of dalzanemdor in participants with MCI or mild dementia due to AD. A total of 174 participants were randomized. About dalzanemdor (SAGE-718) Dalzanemdor (SAGE-718) is a first-in-class investigational NMDA receptor positive allosteric modulator (PAM). Sage has an ongoing placebo-controlled Phase 2 study evaluating dalzanemdor in cognitive impairment associated with Huntington’s Disease. About Sage Therapeutics Sage Therapeutics (Nasdaq: SAGE) is a biopharmaceutical company committed to our mission of pioneering solutions to deliver life-changing brain health medicines, so every person can thrive. Sage developed the only two FDA-approved treatments indicated for postpartum depression and is advancing a robust pipeline to target unmet needs in brain health. Sage was founded in 2010 and is headquartered in Cambridge, Mass. Find out more at www.sagerx.com or engage with us on Facebook , LinkedIn , Instagram , and X . SOURCE: Sage Therapeutics

iStock, selvanegra Sage has decided to discontinue the development of dalzanemdor in Alzheimer’s disease. A study of the candidate in Huntington’s is ongoing, with early data expected later this year. Sage Therapeutics on Tuesday announced that its investigational oral drug candidate dalzanemdor missed the primary endpoint in the Phase II LIGHTWAVE study in Alzheimer’s disease, failing to significantly improve intelligence versus placebo. Details of the failure were scant, with Sage revealing only that the trial data “did not demonstrate a statistically significant difference from baseline in participants treated with dalzanemdor versus placebo” in terms of scores on the Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Test, a validated tool used to evaluate the presence of brain damage or neurodegenerative conditions. WAIS-IV scores were collected at day 84. CEO Barry Greene in a statement said that the biotech is “disappointed” by these results, but hopes that the data generated in LIGHTWAVE will “help to inform future research.” Sage shares tanked 21% in premarket trading on Tuesday in reaction to the news, according to Seeking Alpha . With Tuesday’s setback, Sage will no longer invest in the development of dalzanemdor in Alzheimer’s disease. A Phase II trial in Hungtington’s disease, dubbed DIMENSION, is ongoing and the biotech expects early data from that study to come “later this year,” according to its press release. An oral drug, dalzanemdor is a potentially first-in-class positive allosteric modulator of the NMDA receptor, which is crucial for various brain functions, including cognition, memory and other executive activities. Dalzanemdor works by enhancing the activity of NDMA receptors , in turn potentially addressing core disease pathways in various neurodegenerative conditions. This mechanism of action, however, has yet to result in substantial clinical victories for Sage. In April 2024, the biotech reported that dalzanemdor failed the Phase II PRECEDENT trial in Parkinson’s disease, where it was likewise unable to elicit significant improvements in the WAIS-IV Coding Test versus placebo. As in the case of Alzheimer’s, the failure forced Sage to scrap its Parkinson’s program for dalzanemdor. Even in Huntington’s, where its development is still ongoing, dalzanemdor’s activity appears to be underwhelming. In June 2024, the drug candidate cleared the Phase II SURVEYOR study , eliciting significant improvements in the Huntington’s Disease-Cognitive Assessment Battery composite score. However, analysts at the time were unimpressed. William Blair, for instance, said that it would “remain cautious” regarding dalzanemdor, noting that it does not “view the small numerical changes as definitive.” Beyond dalzanemdor, Sage’s neuro pipeline has had a difficult couple of months. In July 2024, the biotech reported that its Biogen-partnered neuroactive steroid BIIB124 failed the Phase II KINETIC 2 trial in essential tremor. The companies abandoned their development program for BIIB124 in this indication.