BOSTON — Seaport Therapeutics has announced that the first patient has been dosed in its Phase 2b BUOY-1 clinical trial of GlyphAllo™ (SPT-300), a novel oral prodrug of allopregnanolone being developed as a potential first-in-class treatment for major depressive disorder (MDD), with or without anxious distress.
GlyphAllo is part of Seaport’s proprietary Glyph™ platform, which is designed to overcome the delivery limitations of endogenous neuroactive compounds like allopregnanolone. While allopregnanolone has shown rapid antidepressant and anxiolytic effects in previous clinical studies, its therapeutic use has been limited due to formulation and delivery challenges that GlyphAllo aims to address.
“The initiation of BUOY-1 marks a significant milestone for Seaport’s pipeline, bringing us closer to a potential new treatment for major depression, which impacts around 280 million people globally – nearly 60 percent of whom also experience anxious distress,” said Daphne Zohar, Co-Founder and Chief Executive Officer at Seaport Therapeutics. “This is an important step on our journey to deliver new treatments for patients living with depression, anxiety, and other neuropsychiatric conditions.”
The BUOY-1 study is a global, randomized, double-blind, placebo-controlled trial evaluating the efficacy, safety, and tolerability of GlyphAllo in adult patients with MDD, with or without anxious distress—a subtype of depression characterized by significant anxiety symptoms. The trial aims to enroll approximately 360 patients who will receive either GlyphAllo or placebo once daily for six weeks. The primary endpoint is the change in depression severity, as measured by the Hamilton Depression Rating Scale-17 (HAM-D-17), from baseline to the end of the treatment period. Patients who complete the initial phase may enter an open-label extension, receiving GlyphAllo for up to six additional weeks.
“CNS clinical trials are inherently complex, and we are applying our team’s extensive expertise to implement a high-quality study,” said Dr. Antony Loebel, Chief Medical Officer and President of Clinical Development at Seaport Therapeutics. “We are confident that our rigorous clinical trial execution, including an emphasis on the quality of patient enrollment, will build on a proven mechanism and established clinical efficacy, to increase our likelihood of success in developing an effective treatment for patients with depression.”
The BUOY-1 trial follows promising results from earlier clinical studies. In a Phase 1 study, GlyphAllo produced approximately nine times greater exposure to allopregnanolone than previously reported oral versions and reached plasma levels comparable to those achieved with intravenous administration. Electroencephalography and saccadic eye movement tests confirmed that the compound engaged its intended brain targets in a dose-dependent fashion.
In a Phase 2a proof-of-concept study using the Trier Social Stress Test, a validated anxiety model, GlyphAllo significantly reduced salivary cortisol levels at all post-stress time points compared to placebo. The results met the study’s primary endpoint with a highly significant p-value of 0.0001, demonstrating that GlyphAllo effectively modulated stress response through regulation of the hypothalamic-pituitary-adrenal (HPA) axis.
Overall, GlyphAllo has been well tolerated in clinical settings, with mostly mild and transient adverse events. The launch of the BUOY-1 study positions Seaport Therapeutics to continue advancing its neuropsychiatric pipeline, with data from this trial expected to further clarify the role of GlyphAllo as a potential new standard of care for patients with MDD. (Source: IANS)
