お知らせ • Jan 08
MBX Biosciences, Inc. Announces Positive Phase 1 Topline Data for MBX 1416 for the Treatment of Post-Bariatric Hypoglycemia (PBH)
MBX Biosciences, Inc. focused on the discovery and development of novel precision peptide therapies for the treatment of endocrine and metabolic disorders, announced positive results from its Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial of MBX 1416 in healthy adult volunteers. MBX 1416 is the Company’s investigational long-acting glucagon-like peptide 1 (GLP-1) receptor antagonist, being developed for the treatment of PBH. Phase 1 Trial Topline Results; key results study are as follows: MBX 1416 was generally well-tolerated with a favorable safety profile. No MBX 1416 dose-related serious adverse events were observed and the majority of treatment-emergent adverse events were mild or moderate in severity. Injection site reactions (ISR), predominantly characterized by erythema, were commonly observed in both single and multiple ascending dose cohorts. These reactions were mild or moderate in 88% of the subjects with ISRs and resolved within approximately seven days in the MAD cohort. MBX 1416 concentrations increased dose-proportionally in both the SAD and MAD cohorts In the MAD cohort, MBX 1416 median half-life was approximately 90 hours, supporting once-weekly administration, and at steady state the median Tmax was between 36 and 48 hours. In the MAD cohort, MBX 1416 appeared to increase GLP-1 within 60 minutes of a mixed meal tolerance test, suggesting a pharmacodynamic (PD) effect in healthy volunteers that may translate into a therapeutic benefit in PBH patients. Consistent with known GLP-1 antagonism effect on gastric motility, a slight acceleration of gastric emptying was observed with MBX 1416 based on acetaminophen exposure In the drug-drug interaction (DDI) portion of the trial, MBX 1416 was observed to have no meaningful effect on rosuvastatin exposure, a commonly prescribed statin. Phase 1 Trial Design: The Phase 1 clinical trial was a randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MBX 1416 in healthy adult volunteers. The trial was conducted in the United States and enrolled a total of 69 subjects. The single ascending dose (SAD) portion of this Phase 1 trial evaluated 32 healthy adults randomized to receive placebo (n=8) or subcutaneous MBX 1416 doses of 10 mg (n=6), 30 mg (n=6), 100 mg (n=6) and 200 mg (n=6). The multiple ascending dose (MAD) portion of the trial evaluated 23 healthy adults randomized to receive placebo (n=5) or subcutaneous MBX 1416 doses of 10 mg (n=6), 30 mg (as two injections; n=6) and 30 mg (as one injection; n=6). An additional cohort evaluated rosuvastatin and acetaminophen pharmacokinetics in the presence and absence of MBX 1416 (n=14). MBX Biosciences intends to discuss these results with the U.S. Food and Drug Administration (FDA) in an End-of-Phase 1 meeting in mid-2025. Pending alignment with the FDA, a Phase 2 study of MBX 1416 in patients with PBH is anticipated to initiate in the second half of 2025. MBX 1416 is an investigational long-acting glucagon-like peptide-1 (GLP-1) receptor antagonist in development as a potential treatment for PBH. It was designed using the Company’s novel, proprietary PEP™ platform to prevent the occurrence of severe hypoglycemia in individuals with PBH so they can lead healthier and more independent lives. Post-bariatric hypoglycemia (PBH) is a rare and serious complication of bariatric surgery. PBH is characterized by repeated episodes of symptomatic hypoglycemia, triggered by exaggerated secretion of GLP-1 levels following a meal, and can present as early as six months after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy. Hypoglycemic episodes can occur multiple times per day and can periodically manifest with severe symptoms, such as dizziness, confusion, loss of consciousness or seizure. The unpredictability of hypoglycemic episodes and their associated risks may meaningfully hinder daily activities. As a result, the patient burden can be substantial, and many individuals cannot drive, work or live alone. To date, there are no approved pharmacotherapies to treat PBH. As the use of surgery to address metabolic conditions continues to rise, the incidence of PBH is expected to increase, reinforcing the need for safe and effective therapies.