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

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

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

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 (DDW 2025) - No abstract available

Clinical • P2 data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • 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) - No abstract available

Biomarker • P2 data • Fibrosis • Immunology • 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..."

Media quote

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 (Businesswire) - P2a | N=180 | NCT04880031 | Sponsor: Boston Pharmaceuticals | "A second analysis presented at AASLD evaluated population pharmacokinetics (Pop-PK) of BOS-580 in patients with phenotypic NASH enrolled in the Phase 2a trial (n=102)...Once-monthly and bi-weekly dosing regimens for long-acting BOS-580 predicted a similar effect on efficacy biomarkers for NASH based on Pop-PK/PD modeling, supporting the continued development of a once-monthly dose. Differences observed for PD response between the 300 mg and 150 mg once-monthly doses were similar. Results indicate that data were highly correlated with no obvious bias across the Pop-PK and PK/PD models, with most data points within the 90% confidence interval."

P2a data • PK/PD data • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • 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 (Businesswire) - P2a | N=180 | NCT04880031 | Sponsor: Boston Pharmaceuticals | "Boston Pharmaceuticals...announced new data supporting BOS-580...for the treatment of non-alcoholic steatohepatitis (NASH)....These data are being presented on Saturday, Nov. 11, 2023, at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting in Boston....BOS-580 treatment numerically improved insulin resistance, as shown by the reduction of C-peptide (a surrogate for insulin production) levels, across all diabetic sub-populations. BOS-580 treatment numerically improved the percentage of patients who maintained or achieved HbA1c normalization (<5.7%) in the normal and pre-diabetic sub-populations and led to a greater portion of patients in the diabetic sub-population who were able to reduce their HbA1c to <6.5% compared to the placebo group."

P2a data • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

Boston Pharmaceuticals To Present New Phase 2a Data From Investigational BOS-580 NASH Program at AASLD The Liver Meeting 2023 (Businesswire) - "Boston Pharmaceuticals...today announced it will present new data supporting its long-acting dosing schedule and an analysis of treatment in diabetic sub-groups from the Phase 2a Part A clinical program evaluating BOS-580 for the treatment of non-alcoholic steatohepatitis (NASH), at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting, taking place November 10-14, 2023, in Boston."

P2a data • Metabolic Disorders • Non-alcoholic Steatohepatitis

POPULATION PHARMACOKINETIC/PHARMACODYNAMIC MODELING OF HEPATIC FAT FRACTION SUGGESTS EQUIVALENT EFFICACY BETWEEN ONCE MONTHLY AND BI-WEEKLY DOSING OF BOS-580 IN PHENOTYPIC NASH PATIENTS (AASLD 2023) - "Once monthly dosing of BOS-580 appears to be as effective as bi-weekly dosing for the reduction of liver fat in patients with phenotypic NASH, supporting the notion that BOS-580 is an FGF-21 analog capable of once monthly dosing."

Clinical • PK/PD data • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis • FGF21