China-based Brii Biosciences Limited (HKG: 2137) has published the top-line results from a Phase I study for its long-acting, single-injection therapy for postpartum depression (PPD), BRII-296. The open-label, single ascending dose Phase I study assessed the safety, tolerability, and pharmacokinetics (PK) of BRII-296 as a single-injection treatment option for PPD in 116 healthy adults enrolled across 16 cohorts.
Study Design and Results
Three formulation concentrations (100 mg/mL, 200 mg/mL, and 300 mg/mL) were administered via one or more injections at total dose levels of 30 mg, 75 mg, 100 mg, 200 mg, 300 mg, and 600 mg. The study also evaluated oral prophylactic treatment and local steroid administration with BRII-296 (Depo Medrol via co-injection or admix) to manage local injection site reactions (ISRs). The local steroid administration was shown to effectively manage ISRs.
Of the 116 subjects, 98 reported treatment-emergent adverse events (TEAEs), with the majority considered drug-related and attributed to ISRs. Most ISRs were mild to moderate in severity and none led to premature discontinuation from the study. There were no life-threatening TEAEs, TEAEs leading to premature discontinuation, serious adverse events (SAEs), or deaths.
Clinical Efficacy and Future Outlook
The data indicate that a single intramuscular (IM) injection of 600 mg of BRII-296 achieved dose linearity, early drug absorption, and gradual extended-release profiles without the need for dose titration or tapering. This provides confidence that the dose has the potential to achieve clinical efficacy in the treatment of PPD. The selected dose regimen will be evaluated in a Phase II clinical trial, expected to begin this year.
Mechanism of Action
BRII-296 acts as a novel gamma-aminobutyric acid A (GABAa) receptor positive allosteric modulator (PAM) with a unique long-acting formulation. It does not require cessation of breastfeeding and remains effective for weeks after the injection. Designed to provide a rapid, profound, and sustained reduction in depressive symptoms of PPD, BRII-296 may offer substantial clinically meaningful advantages over currently available treatment options.-Fineline Info & Tech
