Development and Characterization of a Long-Acting Allosteric Growth Hormone Receptor Antagonist for Acromegaly
A new long-acting antibody therapy for acromegaly maintains effectiveness for five weeks after a single injection, potentially freeing patients from daily self-injections.
Marea Therapeutics reports the preclinical discovery of MAR002, a half-life-extended monoclonal antibody GHR antagonist that achieves allosteric, non-competitive inhibition of GH signaling—maintaining efficacy even at supraphysiological GH concentrations where competitive antagonists like pegvisomant lose activity. In cynomolgus monkeys, a single IV dose sustained ≥50% IGF-1 suppression for 36 days (vs 15 days for equimolar pegvisomant), supporting development of a monthly or less frequent dosing regimen for acromegaly patients currently on daily self-injections.
What the study was
- Study design
- preclinical
- Population
- Cynomolgus monkey (NHP) and in vitro cell models; target disease: acromegaly patients
- Category
- Drug Development
- Maturity
- Exploratory
- Journal
- Endocrinology
Why it surfaced
First-in-class long-acting allosteric GHR monoclonal antibody antagonist; acromegaly is a rare disease (incidence ~4-7/million) with high unmet need—daily pegvisomant injections limit adherence; >100-fold potency improvement with non-competitive mechanism is compelling; preclinical-only (NHP) limits score despite novelty; Marea Therapeutics/Endocrine Society journal publication.
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