garetosmab (REGN2477) / Regeneron, Sanofi - LARVOL DELTA

OPTIMA: A Study to Assess Safety, Tolerability and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP) (clinicaltrials.gov) - P3 | N=63 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Sep 2026 ➔ Feb 2029

Trial completion date • ACVR1

A Generic Detection Method for the Doping Control Analysis of Fc-Fusion Proteins and Monoclonal Antibodies in Equine Plasma. (PubMed, Drug Test Anal) - "This study is aimed at developing a generic detection method for doping control analysis of nine targeted proteins, each containing the Fc domain of human IgG or IgG from other species in equine plasma, namely, three recombinant Fc-fusion proteins (sotatercept, follistatin-Fc (FST-Fc), and erythropoietin-Fc (EPO-Fc)) and six mAbs (bimagrumab, domagrozumab, garetosmab, landogrozumab, bedinvetmab (Librela), and frunevetmab (Solensia)). The results have demonstrated the method's applicability to equine doping control. This generic method involving affinity purification by Protein A has provided a pragmatic and effective approach to cope with the doping control of novel Fc domain-containing proteins."

Journal • ACVR2A

Select Upcoming 2025 Milestones (GlobeNewswire) - "Report additional data from Phase 1/2 study for DB-OTO (AAV-based gene therapy) in patients with hearing deficit due to variants of the otoferlin gene (mid-2025); Report results from Phase 3 study for pozelimab (C5 antibody) in combination with cemdisiran in myasthenia gravis (second half 2025)....Report results from Phase 2 study for semaglutide in combination with trevogrumab (myostatin antibody) with and without garetosmab (Activin A antibody) in obesity (second half 2025); Report results from Phase 2 study for mibavademab (LEPR agonist antibody) in combination with tirzepatide in obesity (second half 2025); Report results from Phase 3 study for garetosmab (Activin A antibody) in fibrodysplasia ossificans progressiva (FOP) (second half 2025)."

Clinical data • Myasthenia Gravis • Obesity • Rare Diseases

The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation. (PubMed, Metabolism) - "Novel compounds in the pipeline, such as Bimagrumab, Trevogrumab, and Garetosmab-which inhibit activins and myostatin signaling-have demonstrated promise in preventing muscle loss while promoting fat loss...Since this dual therapeutic approach could help address the challenges of muscle and bone loss during weight loss, well-designed studies are needed to optimize these strategies and assess long-term benefits. For the time being, considerations like advanced age and prefrailty may affect the choice of suitable candidates in clinical practice for current and emerging anti-obesity medications due to the associated risk of sarcopenia."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Obesity • Osteoporosis • Sarcopenia

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss and Fat Loss (clinicaltrials.gov) - P2 | N=999 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

Combined GDF8 and Activin A Blockade in Healthy Volunteers: Safety, Efficacy, and Pharmacokinetics (OBESITY WEEK 2024) - "In healthy participants, trevogrumab and garetosmab were generally well tolerated. Combination tx led to greater-than-additive increases in muscle mass, with reductions in fat. Results suggest that GDF8 and activin A are key negative regulators of muscle mass in humans and that combination blockade may be a promising therapeutic approach in muscle atrophy and obesity settings."

Clinical • PK/PD data • Genetic Disorders • Muscular Atrophy • Obesity

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss and Fat Loss (clinicaltrials.gov) - P2 | N=999 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=624 ➔ 999 | Trial primary completion date: Jun 2026 ➔ Feb 2026

Enrollment change • Trial primary completion date • Genetic Disorders • Obesity

Comparison of PET/CT versus CT only in the assessment of new heterotopic ossification bone lesions in patients with fibrodysplasia ossificans progressiva. (PubMed, Bone) - P2 | "LUMINA-1, a phase 2, randomized, double-blind study (NCT03188666), evaluated the safety and efficacy of garetosmab, an anti-activin A antibody, versus placebo in adult patients with FOP...CT-only imaging showed similar performance to PET/CT in the detection and characterization of new HO lesions. CT-only imaging therefore is a viable option for the assessment of therapies on new HO in patients with FOP."

Clinical • Journal • Rare Diseases

INHBA promotes tumor growth and induces resistance to PD-L1 blockade by suppressing IFN-γ signaling. (PubMed, Acta Pharmacol Sin) - "Furthermore, the activin A-specific antibody garetosmab improved anti-tumor immunity and its combination with the anti-PD-L1 antibody atezolizumab showed a superior therapeutic effect to monotherapy with garetosmab or atezolizumab. We demonstrate that INHBA and activin A are involved in anti-tumor immunity by inhibiting the IFN-γ signaling pathway, which can be considered as potential targets to improve the responsive rate of PD-1/PD-L1 blockade."

IO biomarker • Journal • Breast Cancer • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRCA • CD4 • CD8 • CXCL10 • CXCL9 • IFNG • INHBA

Characterization of flare-ups and impact of Garetosmab in adults with Fibrodysplasia Ossificans Progressiva: a post hoc analysis of the randomized, double-blind, placebo-controlled LUMINA-1 trial. (PubMed, J Bone Miner Res) - P2 | "In this analysis, 71% of placebo-treated adults with FOP experienced flare-ups over 28 weeks, which were associated with an increased volume of newly formed heterotopic bone. Garetosmab reduced the severity and duration of flare-ups with effects sustained during the entire trial."

Clinical • Journal • Retrospective data • Pain • Rare Diseases

OPTIMA: A Study to Assess Safety, Tolerability and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP) (clinicaltrials.gov) - P3 | N=63 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2026 ➔ Oct 2026 | Trial primary completion date: Apr 2025 ➔ Jul 2025

Enrollment closed • Trial completion date • Trial primary completion date • ACVR1

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss and Fat Loss (clinicaltrials.gov) - P2 | N=624 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

The Effect of Combined Activin A and Myostatin Blockade on Body Composition—A Phase 1 Trial (ADA 2024) - "Combined administration of trevogrumab and garetosmab led to dose-dependent, greater‑than‑additive increases in TMV and lean mass, while decreasing fat mass in healthy participants."

P1 data • Diabetes • Metabolic Disorders

Case Study of New Lesion Formation in FOP Patients by 18F-NaF PET/CT Imaging (ENDO 2024) - P2 | "LUMINA-1, a phase 2, randomized, double-blind study (NCT03188666), evaluated the safety and efficacy of garetosmab, an anti-activin A antibody, versus placebo in adult patients with FOP...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO."

Case study • Clinical • Pain • Rare Diseases

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss and Fat Loss (clinicaltrials.gov) - P2 | N=624 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss and Fat Loss (clinicaltrials.gov) - P2 | N=624 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss and Fat Loss (clinicaltrials.gov) - P2 | N=624 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Genetic Disorders • Obesity

How Activin A Became a Therapeutic Target in Fibrodysplasia Ossificans Progressiva. (PubMed, Biomolecules) - "This discovery led to the clinical development of garetosmab, an investigational antibody that blocks Activin A. In a phase 2 trial, garetosmab inhibited new heterotopic bone lesion formation in FOP patients. In contrast, antibodies to ACVR1 activate ACVR1 and promote HO in FOP mice. Beyond their potential clinical relevance, these findings have enhanced our understanding of FOP's pathophysiology, leading to the identification of fibroadipogenic progenitors as the cells that form HO, and the discovery of non-signaling complexes between Activin A and wild type ACVR1 and their role in tempering HO, and are also starting to inform biological processes beyond FOP."

Journal • Review • Genetic Disorders • ACVR1

Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial. (PubMed, Nat Med) - P2 | "Further investigation of garetosmab in FOP is ongoing. ClinicalTrials.gov identifier NCT03188666 ."

Clinical • Journal • P2 data • Pain • Rare Diseases

Flare-Ups in Patients with Fibrodysplasia Ossificans Progressiva Reduced by Garetosmab Treatment: LUMINA-1 Data (ENDO 2023) - P2 | "Patients treated with garetosmab experienced significant and sustained reductions in the frequency, duration, and severity of flare-ups. The ability of garetosmab to reduce flare-up events may provide a clinically meaningful benefit for patients with FOP.*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins."

Clinical • Musculoskeletal Pain • Pain • ACVR1

Garetosmab in Fibrodysplasia Ossificans Progressiva: Clinical Pharmacology Results From the Phase 2 LUMINA-1 Trial. (PubMed, J Clin Pharmacol) - P2 | "There were no trends that suggested patients with higher serum exposures to garetosmab were more likely to experience a reduction in heterotopic ossification or adverse events. Garetosmab is being further evaluated in the phase 3 OPTIMA trial."

Journal • P2 data

New Heterotopic Ossification Lesions in Patients with Fibrodysplasia Ossificans Progressiva Measured by PET/CT vs CT Only (ENDO 2023) - P2 | "CT imaging showed similar performance to PET/CT in the detection and characterization of new HO lesions and provides a viable option for the assessment of therapies that may inhibit the formation of new HO lesions in patients with FOP."

Clinical • Pain • Rare Diseases • ACVR1

New Heterotopic Ossification Lesions in Patients with Fibrodysplasia Ossificans Progressiva Measured by PET/CT vs CT Only (ENDO 2023) - P2 | "Garetosmab, a fully human monoclonal antibody against activin-A, is being investigated for the prevention of new HO lesions in patients with FOP... CT imaging showed similar performance to PET/CT in the detection and characterization of new HO lesions and provides a viable option for the assessment of therapies that may inhibit the formation of new HO lesions in patients with FOP.*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference."

Clinical • Pain • Rare Diseases • ACVR1

Pharmacokinetics and Pharmacodynamics of Garetosmab in Patients with Fibrodysplasia Ossificans Progressiva (ENDO 2023) - P2, P3 | "PK steady state was reached within approximately 16 weeks of starting garetosmab treatment, and there were no trends suggesting patients with higher serum exposures to functional garetosmab were more likely to experience adverse events. Incidence of anti-garetosmab antibodies was low and concentrations of BMP9 in serum had no apparent association with epistaxis. Garetosmab is being further evaluated in the phase 3 OPTIMA trial (NCT05394116).*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation."

Clinical • PK/PD data • Infectious Disease • Rare Diseases

OPTIMA: The Examination of Safety and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP) (clinicaltrials.gov) - P3 | N=66 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • ACVR1