Preclinical, randomized phase 1, and compassionate use evaluation of REGN4461, a leptin receptor agonist antibody for leptin deficiency
Altarejos J, Pangilinan J, Podgrabinska S, Akinci B, Foss-Freitas M, Neidert A, Ray Y, Zheng W, Kim S, Kamat V, Huang M, Min S, Mastaitis J, Dominguez-Gutierrez G, Kim J, Stevis P, Huang T, Zambrowicz B, Olson W, Godin S, Bradley E, Gewitz A, Baker M, Hench R, Davenport M, Chenevert T, DiPaola F, Yancopoulos G, Murphy A, Herman G, Musser B, Dansky H, Harp J, Gromada J, Sleeman M, Oral E, Olenchock B. Preclinical, randomized phase 1, and compassionate use evaluation of REGN4461, a leptin receptor agonist antibody for leptin deficiency. Science Translational Medicine 2023, 15: eadd4897. PMID: 37992152, DOI: 10.1126/scitranslmed.add4897.Peer-Reviewed Original ResearchConceptsLeptin concentrationsBody weightHepatic steatosisAdipose-derived hormone leptinClass 3 obesityCompassionate use treatmentHigher baseline leptinLeptin knockout miceAcceptable safety profileLower leptin concentrationsPresence of leptinHuman monoclonal antibodyLeptin receptor signalingTreatment of individualsPhase 1Baseline leptinLepr signalingLeptin deficiencyMetabolic sequelaeLiver diseaseClinical benefitSafety profileInsulin resistanceBlood glucoseInsulin sensitivity207-OR: Myostatin Inhibition Synergizes with GLP-1R Agonism to Accelerate Weight Loss in Male, Obese Nonhuman Primates
MASTAITIS J, GOMEZ D, LE ROUZIC V, STEC M, KHAN N, NA E, MCWILLIAMS T, MIN S, SLEEMAN M. 207-OR: Myostatin Inhibition Synergizes with GLP-1R Agonism to Accelerate Weight Loss in Male, Obese Nonhuman Primates. Diabetes 2023, 72 DOI: 10.2337/db23-207-or.Peer-Reviewed Original ResearchIncreased lean massFat massLean massWeight lossGlucagon-like peptide-1 receptor agonistsClinically meaningful weight lossPeptide-1 receptor agonistsBlockade of myostatinCaloric restrictionGLP-1RA treatmentWeeks of treatmentHuman monoclonal antibodyInduce clinically meaningful weight lossMediators of skeletal muscle atrophyStandard-of-careDiet-induced obese miceSkeletal muscle massSkeletal muscle atrophyReduced fat massQuality of weight lossMale cynomolgus monkeysAccelerated weight lossObese patentsReceptor agonistsAnti-obesity agents