fazpilodemab (BFKB8488A) / Roche - LARVOL DELTA

BANFF: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BFKB8488A Compared With Placebo in Participants With Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2 | N=46 | Terminated | Sponsor: Genentech, Inc. | Completed ➔ Terminated; The study was terminated due to strategic business reasons.

Trial termination • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

Simulation-based evaluation of personalized dosing approaches for anti-FGFR/KLB bispecific antibody fazpilodemab. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Dynamic simulation of personalized dosing strategies demonstrated that the AE-based personalized dosing is the most effective approach for optimizing the benefit-risk profiles. The approach presented here can be a useful framework for quantifying the benefit of personalized dosing for drugs with narrow therapeutic windows."

Biomarker • Clinical • Journal • Observational data • P2 data • P4 data • Retrospective data • Review • Gastrointestinal Disorder • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • FGFR

A PHASE II TRIAL OF FAZPILODEMAB (BFKB8488A), A FIBROBLAST GROWTH FACTOR RECEPTOR 1C/KLOTHO Β AGONIST, IN PATIENTS WITH METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS (MASH) (AASLD 2023) - P2 | "In patients with MASH, fazpilodemab was adequately tolerated and demonstrated an acceptable safety profile. Improvements in liver enzymes were observed following fazpilodemab, though the early study termination and small sample size in this study limit the interpretation of clinical effect."

Clinical • Late-breaking abstract • P2 data • Diabetes • Fibrosis • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Novel Coronavirus Disease • Type 2 Diabetes Mellitus • FGFR1

BANFF: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BFKB8488A Compared With Placebo in Participants With Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2 | N=46 | Completed | Sponsor: Genentech, Inc. | Active, not recruiting ➔ Completed | N=260 ➔ 46

Enrollment change • Trial completion • Hepatology • Non-alcoholic Steatohepatitis

THE BISPECIFIC ANTI-FGFR1/KLB AGONIST ANTIBODY bFKB1 ATTENUATES NON-ALCOHOLIC STEATOHEPATITIS AND ATHEROSCLEROSIS IN LDLR-/-.LEIDEN MICE (AASLD 2022) - "The bispecific anti-FGFR1/KLB agonist antibody has strong metabolic effects in HFD-fed Ldlr-/-.Leiden mice. These beneficial effects are associated with a reduction in liver steatosis and inflammation as well as atherosclerosis. Liver fibrosis was not affected within the treatment period studied, but analysis of new collagen formation and profibrotic transcriptional programs indicate that the treatment may have antifibrotic potential in a longer treatment duration in line with recent clinical results of FGF21 mimetic class of molecules."

Late-breaking abstract • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Non-alcoholic Steatohepatitis • Obesity • FGF21 • FGFR1

GREATER EFFICACY PREDICTED FOR FGFR1/BETA-KLOTHO RECEPTOR AGONISTS THAT ACHIEVE 60% OR GREATER INCREASES IN SERUM ADIPONECTIN (AASLD 2022) - "Efficacy was predicted for multiple agonists of the FGFR1/KLB, including pegbelfermin, efruxifermin, Bio89-100, and BFKB8488A. Greater treatment-induced adiponectin production likely mediates enhanced predicted efficacy with FGFR1/KLB agonists. Compounds and doses that achieve >60% increases in serum adiponectin are predicted to have greatest benefits in multiple NASH patient measurements."

Clinical • Fibrosis • Hepatology • Immunology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • FGF21 • FGFR1

FGFR1/Klothoβ agonist BFKB8488A improves lipids and liver health markers in patients with diabetes or NAFLD: a phase 1b randomized trial. (PubMed, Hepatology) - P1 | "BFKB8488A was adequately tolerated in patients with T2DM or NAFLD, leading to triglyceride reduction, HDL improvements, and trends in improvement in markers of liver health for both populations, and marked liver fat reduction in patients with NAFLD. (ClinicalTrials.gov:NCT03060538)."

Journal • P1 data • Diabetes • Hepatology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Type 2 Diabetes Mellitus • FGFR1

BANFF: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BFKB8488A Compared With Placebo in Participants With Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2 | N=260 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: May 2022 ➔ Jan 2023 | Trial primary completion date: Mar 2022 ➔ Jan 2023

Trial completion date • Trial primary completion date • Hepatology • Non-alcoholic Steatohepatitis

BANFF: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BFKB8488A Compared With Placebo in Participants With Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2 | N=260 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Non-alcoholic Steatohepatitis

[VIRTUAL] ANTI-FGFR1/KLB THERAPY IS ASSOCIATED WITH SHIFT IN OVERALL MICROBIOTA COMPOSITION AND INCREASED CAPACITY FOR SCFA PRODUCTION IN T2D (DDW 2021) - P1 | "This shift in β-diversity was accompanied by increased abundance of Veillonella, Erysipelatoclostridium, and Pauljensia and decreased Ruthenibacterium, Agathobacter, and Ruminococcus-A compared to baseline. Furthermore, analysis of inferred metagenomes suggests increased capacity for SCFA synthesis following treatment, supporting future examination of SCFA concentrations in these subjects.These findings indicate BFKB8488A treatment altered GI microbiome composition in T2D, enriching for SCFA producing microbes."

Gastrointestinal Disorder • Metabolic Disorders • FGF21 • FGFR1

[VIRTUAL] MATHEMATICAL MODELING WITH NAFLDSYM SUPPORTS THE ROLE OF ADIPONECTIN IN THE REDUCTION OF STEATOSIS BY THE ANTI-FGFR1/KLB BISPECIFIC ANTIBODY (AASLD 2020) - "The hypothesis that BFKB8488A-induced increases in Adpn mediate the observed effects on liver fat in NAFLD patients is consistent with NAFLDsym simulations. The similarity between the clinical observations and model predictions utilizing the simulated mechanistic effects of Adpn on hepatic lipid pathways suggests that Adpn participates in mediating the potentially beneficial response to BFKB8488A."

Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • FGFR1

Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans. (PubMed, Proc Natl Acad Sci U S A) - "In a randomized, placebo-controlled, single ascending-dose study in overweight/obese human participants, subcutaneous BFKB8488A injection caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that specific activation of the FGFR1/KLB complex in humans can be used as therapy for obesity-related metabolic defects."

Journal • Genetic Disorders • Metabolic Disorders • Obesity • FGFR1

BANFF: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BFKB8488A Compared With Placebo in Participants With Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2; N=260; Recruiting; Sponsor: Genentech, Inc.; Initiation date: Jul 2020 ➔ Sep 2020

Clinical • Trial initiation date • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • MRI

A Multiple Ascending Dose Study to Evaluate Safety and Tolerability of BFKB8488A in Participants With Type 2 Diabetes Mellitus and Participants With Non-Alcoholic Fatty Liver Disease (clinicaltrials.gov) - P1; N=154; Completed; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Completed

Trial completion

BANFF: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BFKB8488A Compared With Placebo in Participants With Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2; N=260; Recruiting; Sponsor: Genentech, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

BANFF: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BFKB8488A Compared With Placebo in Participants With Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2; N=260; Not yet recruiting; Sponsor: Genentech, Inc.

Clinical • New P2 trial

MULTIPLE DOSES OF AN ANTI-FGFR1/KLB BISPECIFIC ANTIBODY (BFKB8488A) ARE ASSOCIATED WITH A DECREASE IN HEPATIC FAT IN PATIENTS WITH NAFLD (AASLD 2019) - "In patients with NAFLD, well-tolerated doses of BFKB8488A were highly effective at decreasing hepatic fat fraction and improving liver health. The translation of these effects into clinical efficacy is being further evaluated in a Phase 2 non-alcoholic steatohepatitis (NASH) study."

Clinical • Late-breaking abstract • FGFR1

A BISPECIFIC ANTIBODY TO FGFR1/KLB, BFKB8488A, IMPROVES LIPID PROFILE, MARKERS OF FIBROGENESIS AND LIVER HEALTH IN PATIENTS WITH TYPE 2 DIABETES - PRELIMINARY RESULTS FROM A PHASE 1b STUDY (AASLD 2019) - "BFKB8488A was safe, adequately tolerated, and highly effective at improving markers of cardiometabolic and liver health. Ongoing studies will evaluate the translation of these pharmacodynamic effects into clinical efficacy in NASH and related diseases."

Clinical • P1 data • FGFR1

A Multiple Ascending Dose Study to Evaluate Safety and Tolerability of BFKB8488A in Participants With Type 2 Diabetes Mellitus and Participants With Non-Alcoholic Fatty Liver Disease (clinicaltrials.gov) - P1; N=154; Active, not recruiting; Sponsor: Genentech, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Multiple Ascending Dose Study to Evaluate Safety and Tolerability of BFKB8488A in Participants With Type 2 Diabetes Mellitus and Participants With Non-Alcoholic Fatty Liver Disease (clinicaltrials.gov) - P1; N=136; Recruiting; Sponsor: Genentech, Inc.; Trial completion date: Jul 2019 ➔ Dec 2019; Trial primary completion date: Jul 2019 ➔ Dec 2019

Clinical • Trial completion date • Trial primary completion date