efimosfermin alfa (BOS-580) / Novartis, Boston Pharma, GSK - LARVOL DELTA

GSK to acquire efimosfermin, a phase III-ready potential best-in-class specialty medicine to treat and prevent progression of steatotic liver disease (SLD) (Businesswire) - "GSK plc...and Boston Pharmaceuticals...announced that they have entered into an agreement under which GSK will acquire Boston Pharmaceuticals’ lead asset, efimosfermin alfa....Under the agreement, GSK will pay $1.2 billion upfront, with potential for additional success-based milestone payments totalling $800 million....The acquisition of efimosfermin is highly aligned to GSK’s R&D focus on science related to the immune system and is further evidence of the company’s intent to build on its deep understanding of fibrosis and auto-inflammation to develop precision interventions that stop and reverse disease progression....Efimosfermin will significantly expand our hepatology pipeline and provide us the opportunity to develop a new potential best-in-class medicine with first launch expected in 2029."

Commercial • Launch • Metabolic Dysfunction-Associated Steatohepatitis

ONCE MONTHLY EFIMOSFERMIN ALFA IMPROVES FAST AND FIB-4 COMPOSITE BIOMARKER SCORES FOR MASH STAGE F2/F3 FIBROSIS IN A 24-WEEK PHASE 2 TRIAL (DDW 2025) - P2 | "Once monthly efimosfermin treatment resulted in significant reductions in FAST and FIB-4 composite biomarker scores. FIB-4 scores were rapidly reduced at week 4 and remained low throughout the trial. In the phase 2 trial, efimosfermin improved composite biomarkers in subjects with MASH stage F2/F3 fibrosis, which may translate to reduced liver-related events in longer term trials."

Biomarker • P2 data • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • FGF21

4200: SOA - Update on MASLD Therapies Pipeline (DDW 2025) - "Description: This State-of-the-Art session provides a timely update on the evolving MASLD therapies pipeline, featuring insights into emerging pharmacologic agents and real-world data on current treatments. Topics include the impact of SGLT-2 and GLP-1 receptor agonists on cirrhosis outcomes, eligibility criteria for resmetirom therapy, and phase 2 results for efimosfermin alfa in MASH with fibrosis.Learning Objectives:• Describe the impact of SGLT-2 and GLP-1 receptor agonists on cirrhosis outcomes• Identify the eligibility criteria for resmetirom therapy• Discuss phase 2 results for efimosfermin alfa in MASH with fibrosis"

Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

ONCE-MONTHLY EFIMOSFERMIN ALFA (BOS-580) IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS WITH F2/F3 FIBROSIS: RESULTS FROM A 24 WEEK, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2 TRIAL (DDW 2025) - P2 | No abstract available

Clinical • P2 data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) MASH (clinicaltrials.gov) - P2 | N=42 | Recruiting | Sponsor: Boston Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Boston Pharmaceuticals to Present the Effect of Efimosfermin Alfa on Collagen Biomarkers in Patients with F2 and F3 MASH at EASL Congress 2025 (Businesswire) - P2 | N=231 | NCT04880031 | Sponsor: Boston Pharmaceuticals | "Boston Pharmaceuticals...announced it will present results from an analysis of its Phase 2 study in participants with stage F2 and F3 fibrosis due to MASH. The findings will be presented at the European Association for the Study of the Liver (EASL) Congress 2025, May 7-10, in Amsterdam...'In the analysis, efimosfermin demonstrated improvements in biomarkers related to collagen and a reduction in liver scarring among patients with moderate to advanced liver fibrosis (stages F2-F3) caused by metabolic dysfunction-associated steatotic liver disease.'....Substantial and rapid improvements in cardiometabolic benefits, such as liver fat reduction and improved glycemic control, were also observed in MASH patients with obesity and diabetes. Efimosfermin was generally well tolerated in the Phase 2 study..."

P2 data • Metabolic Dysfunction-Associated Steatohepatitis

Boston Pharmaceuticals to Present State-of-the-Art Lecture and Poster for Once-monthly Efimosfermin Alfa at Digestive Disease Week 2025 (Businesswire) - "Boston Pharmaceuticals...announced it will present immunogenicity and biomarker analyses from its Phase 2 study, in participants with stage F2 and F3 fibrosis due to MASH. The results will be presented in a state-of-the-art lecture and poster at Digestive Disease Week (DDW) in San Diego, May 3-6, 2025....Efimosfermin clinical program to advance to Phase 3 pivotal study in fourth quarter of 2025."

New P3 trial • P2 data • Metabolic Dysfunction-Associated Steatohepatitis

Efimosfermin alfa once monthly treatment improves collagen biomarker profiles and rapidly induces histological fibrosis regression in subjects with MASH stage F2-F3 fibrosis in a 24-week phase 2 trial (EASL 2025) - P2 | "Efimosfermin treatment rapidly induces fibrosis regression in subjects with MASH stage F2/F3 fibrosis as evidenced by significant improvements in ECM remodeling during a 24-week Phase 2 trial. Efimosfermin showed improvements in collagen biomarkers regardless of baseline MASH stage F2 or F3 fibrosis. Consistent with histology data, decreases in the Pro-C3/CTX-III ratio show a shift in the overall balance between fibrogenesis and fibrolysis towards fibrosis clearance in the efimosfermin treated subjects with MASH stage F2/F3 fibrosis."

Biomarker • Clinical • P2 data • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) MASH (clinicaltrials.gov) - P2 | N=42 | Not yet recruiting | Sponsor: Boston Pharmaceuticals

New P2 trial • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Once-Monthly Efimosfermin Alfa (BOS-580) in Metabolic Dysfunction-Associated Steatohepatitis With F2/F3 Fibrosis: Results From a 24-Week, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial. (PubMed, Gastroenterol Hepatol (N Y)) - No abstract available

Clinical • Journal • P2 data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

BOS-580-201: A Study of BOS-580 in Obese Subjects At Risk For, or with Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) with an Extension (clinicaltrials.gov) - P2 | N=231 | Active, not recruiting | Sponsor: Boston Pharmaceuticals | Trial completion date: Jul 2026 ➔ Nov 2025 | Trial primary completion date: Jul 2026 ➔ Nov 2025

Biopsy • Trial completion date • Trial primary completion date • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

BOS-580-201: A Study of BOS-580 in Obese Subjects At Risk For, or with Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) with an Extension (clinicaltrials.gov) - P2 | N=231 | Active, not recruiting | Sponsor: Boston Pharmaceuticals | Recruiting ➔ Active, not recruiting

Biopsy • Enrollment closed • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

Boston Pharmaceuticals to Announce Positive Phase 2 Data on Efimosfermin Alfa (BOS-580) in F2/F3 MASH During Late-Breaking Oral Presentation at AASLD 2024, The Liver Meeting (Businesswire) - P2 | N=245 | NCT04880031 | Sponsor: Boston Pharmaceuticals | "Boston Pharmaceuticals...today announced positive results from a Phase 2 study evaluating the safety and efficacy of once-monthly efimosfermin alfa....Treatment with efimosfermin led to significant improvements in fibrosis ≥1 stage without worsening of MASH, and MASH resolution without worsening of fibrosis over 24 weeks. In the study, efimosfermin demonstrated a favorable tolerability profile. These topline results will be presented on Nov. 19 in a late-breaking oral presentation at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting,® Nov. 15-19, 2024, in San Diego....In addition, study participants treated with efimosfermin showed rapid and significant improvement in fibrosis biomarkers and significant reductions in non-invasive markers of liver injury and liver fat over the study period."

P2 data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Boston Pharmaceuticals to Present Phase 2 Biopsy Results for Long-Acting, Once-Monthly FGF21 Analogue Efimosfermin Alfa (BOS-580) in F2 and F3 MASH in Late-Breaking Oral Presentation at AASLD, The Liver Meeting 2024 (Businesswire) - "Boston Pharmaceuticals...today announced it will present key results including histologic responses from a Phase 2 study evaluating the safety and efficacy of the investigational agent, efimosfermin alfa (formerly known as BOS-580), in participants with stage F2 and F3 fibrosis due to metabolic dysfunction-associated steatohepatitis (MASH) as a late-breaking oral presentation at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting (Nov. 15-19, 2024 in San Diego)."

P2 data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) With an Extension (clinicaltrials.gov) - P2 | N=245 | Recruiting | Sponsor: Boston Pharmaceuticals | Active, not recruiting ➔ Recruiting | Trial completion date: Dec 2024 ➔ Jul 2026 | Trial primary completion date: Dec 2024 ➔ Jul 2026

Biopsy • Enrollment open • Trial completion date • Trial primary completion date • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) With an Extension (clinicaltrials.gov) - P2 | N=205 | Active, not recruiting | Sponsor: Boston Pharmaceuticals | N=82 ➔ 205

Biopsy • Enrollment change • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

BOS-580, a long-acting FGF-21 analogue, treatment shows beneficial changes in the circulating lipidome and improves MASEF score in patients with phenotypic metabolic dysfunction-associated steatohepatitis in a phase 2a randomized, placebo-controlled, 12-week study (EASL-ILC 2024) - "Treatment with once-monthly and bi-weekly BOS-580 improves the MASEF score at 12 weeks. Improvement of the MASEF score suggests reduction of at-risk MASH."

Clinical • P2a data • Fibrosis • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • FGF21

Boston Pharmaceuticals Presents Data at EASL Congress 2024 Showing Treatment With Long-acting FGF21 Analogue, BOS-580, Improved Lipid Profiles in Patients with Phenotypic MASH (Businesswire) - P2a | N=82 | NCT04880031 | Sponsor: Boston Pharmaceuticals | "Boston Pharmaceuticals...announced new Phase 2a data demonstrating the positive impact of BOS-580...on the circulating lipidome and changes in the metabolomics advanced steatohepatitis fibrosis (MASEF) score in patients with phenotypic metabolic dysfunction-associated steatohepatitis (MASH). The data will be presented at the European Association for the Study of the Liver (EASL) Congress 2024, held from June 5-8 in Milan, Italy....Eighty-eight percent of patients treated with BOS-580 achieved reductions in their composite MASEF scores, compared to 33% in the placebo group. Treatment with BOS-580 also improved MASEF risk classification by decreasing the number of patients identified to be at-risk for MASH from 20% at baseline to 2% at 12 weeks, compared to an increase from 17% at baseline to 20% at 12 weeks in the placebo group."

P2a data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2 | N=82 | Active, not recruiting | Sponsor: Boston Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=180 ➔ 82

Biopsy • Enrollment change • Enrollment closed • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

Fibroblast Growth Factor 21 in the Diagnosis and Treatment of Metabolic Disorders (ENDO 2024) - "Since native FGF21 has poor pharmacodynamic properties (e.g., short half-life and proteolytic cleavage by proteases), long-acting FGF21 analogs (e.g., LY2405319, PF-05231023, pegozafermin, AKR-001, and LLF580) have been synthesized and tested in clinical trials for the treatment of obesity, NAFLD, dyslipidemia, and type 2 diabetes. FGF21 is a predominantly liver-derived peptide hormone regulating energy expenditure and metabolism of lipids and glucose. Serum FGF21 levels are increased in several metabolic disorders including obesity, NAFLD, dyslipidemia, and type 2 diabetes. FGF21 is an attractive target for the treatment of these metabolic disorders."

Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Hepatology • Infectious Disease • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Nephrology • Obesity • Renal Disease • Septic Shock • Type 2 Diabetes Mellitus • FGF21

VIDEO: Investigational FGF-21 improves liver fat, glycemic control markers in MASH, diabetes (Healio) - P2a | N=180 | NCT04880031 | Sponsor: Boston Pharmaceuticals | "According to results, C-peptide levels were reduced across all subpopulations treated with BOS-580 vs. placebo, indicating improvement in insulin resistance. HbA1c levels also declined across all groups on BOS-580, with greater reductions in the diabetic subpopulation. Further, treatment with BOS-580 improved the percentage of participants who maintained or achieved HbA1c normalization, with 31% of patients in the diabetic subpopulation reducing HbA1c to less than 6.5% compared with 11.1% on placebo."

P2a data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

VIDEO: Investigational FGF-21 improves liver fat, glycemic control markers in MASH, diabetes (Healio) - "Loomba continued, 'We are very hopeful that these data based on noninvasive biomarkers translate into histologic response.'"

Video

A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Boston Pharmaceuticals | Phase classification: P2a ➔ P2

Biopsy • Phase classification • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

Boston Pharmaceuticals Presents Data at NASH-TAG 2024 Demonstrating Low Immunogenicity Over Time With Long-acting FGF21 Analogue, BOS-580, for MASH (Businesswire) - P2a | N=180 | NCT04880031 | Sponsor: Boston Pharmaceuticals | "Boston Pharmaceuticals...announced additional Phase 2 data supporting the low risk of immunogenicity and positive clinical effects associated with BOS-580, the company’s investigational, long-acting fibroblast growth factor 21 (FGF21) analogue for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), also known as non-alcoholic steatohepatitis (NASH). The data were presented at NASH-TAG 2024 (Jan. 4-6, 2024) in Park City, Utah....Results of this analysis show treatment with BOS-580 led to significant reductions across composite scores for Fibroscan-AST (FAST), Fibrosis-4 Index (FIB-4), Aspartate aminotransferase-to-platelet ratio index (APRI) and ADAPT. The responses observed were rapid, within one to two weeks, and were sustained over the 12-week study, suggesting BOS-580 treatment may lead to clinical benefit in MASH patients."

P2a data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Boston Pharmaceuticals Announces Positive Phase 2a Data Supporting Once-monthly Dosing With Investigational BOS-580 in NASH and Treatment Effects in Diabetic Subgroups at AASLD The Liver Meeting 2023 (BioSpace) - '"BOS-580 treatment appears promising in maintaining healthy HbA1c levels among patients with phenotypic NASH, irrespective of their concurrent type 2 diabetes status. Our analysis showed that BOS-580 performed consistently well across all diabetic sub-populations in the Phase 2a clinical study,' said Rohit Loomba..."

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