MBX Biosciences has 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 post-bariatric hypoglycaemia (PBH). MBX 1416 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.
The Phase 1 clinical trial was a randomised, 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 randomised 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 randomised 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).
Key results from the study are as follows:
MBX 1416 was generally well-tolerated with a favourable 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.
MBX Biosciences intends to discuss these results with the 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.
“We are encouraged by the positive topline Phase 1 results in healthy volunteers that showed MBX 1416 was generally well-tolerated with a favourable safety profile and a promising pharmacokinetic profile supportive of once-weekly dosing,” said Kent Hawryluk, President and Chief Executive Officer of MBX Biosciences. “We also observed an apparent increase in GLP-1 peak during the first hour after a mixed meal tolerance test, which is an encouraging signal that we believe may translate into a therapeutic benefit in patients with PBH. Based on these results, we intend to initiate a Phase 2 study in patients with PBH in the second half of 2025 to further optimize dosing, pending alignment with the FDA on our proposed study design.”
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