The Liver Meeting

The Liver Meeting

Source:

Loomba R. Efficacy and safety of pegbelfermin in patients with nonalcoholic steatohepatitis and stage 3 fibrosis: Results from the phase 2b, randomized, double blind, placebo-controlled FALCON 1 study. Presented at: The Liver Meeting Digital Experience; Nov. 12-15, 2021 (virtual meeting).

Disclosures: Loomba reports receiving study funding from Bristol Myers Squibb; consultancy fees from Arrowhead Pharmaceuticals, Bird Rock Bio, Enanta Pharmaceuticals, Galmed Pharmaceuticals, Gir Pharmaceuticals, GRI Bio, Madrigal Pharmaceuticals, Metacrine and NGM Pharmaceuticals; and research grants from Allergan, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Galectin Therapeutics, Galmed Pharmaceuticals, GE, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Janssen Pharmaceuticals, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Pfizer, Prometheus, Siemens and Sirius.
November 16, 2021
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Pegbelfermin improves markers of fibrosis in NASH

Source:

Loomba R. Efficacy and safety of pegbelfermin in patients with nonalcoholic steatohepatitis and stage 3 fibrosis: Results from the phase 2b, randomized, double blind, placebo-controlled FALCON 1 study. Presented at: The Liver Meeting Digital Experience; Nov. 12-15, 2021 (virtual meeting).

Disclosures: Loomba reports receiving study funding from Bristol Myers Squibb; consultancy fees from Arrowhead Pharmaceuticals, Bird Rock Bio, Enanta Pharmaceuticals, Galmed Pharmaceuticals, Gir Pharmaceuticals, GRI Bio, Madrigal Pharmaceuticals, Metacrine and NGM Pharmaceuticals; and research grants from Allergan, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Galectin Therapeutics, Galmed Pharmaceuticals, GE, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Janssen Pharmaceuticals, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Pfizer, Prometheus, Siemens and Sirius.
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Pegbelfermin was safe and effective in improving markers of steatosis, fibrosis and inflammation among patients with nonalcoholic steatohepatitis with stage 3 fibrosis, according to a presentation at The Liver Meeting Digital Experience.

“FGF21 is a non-mitogenic hormone predominantly secreted by the liver which is an important regulator of glucose and lipid metabolism. FGF21 may have direct and indirect beneficial effects on NASH and NASH-related fibrosis. Healthy liver secretes endogenous FGF21. A main problem for developing pharmacology has been that the half-life is very short,” Rohit Loomba, MD, MHSc, professor of medicine in the division of gastroenterology and adjunct professor in the division of epidemiology at the University of California San Diego, said. “Pegbelfermin (PGBF) is a PEGylated recombinant human FGF21 analog with a prolonged half-life supporting weekly dosing. We previously conducted a phase 2 trial in patients with biopsy proven NASH who underwent advanced imaging modalities where we showed improvement in MRI PDF and various other noninvasive biomarkers.”

study data

Aimed to evaluate the safety and efficacy of PGBF, researchers enrolled 197 patients (mean age, 57 years; 59% women; 85% white) with NASH and stage 3 liver fibrosis in a randomized, double-blind, placebo-controlled study (FALCON 1). Patients were randomly assigned to receive subcutaneous doses of either PGBF 10 mg (n = 49), PGBF 20 mg (n = 50), PGBF 40 mg (n = 49) or placebo (n = 49) once weekly for 48 weeks; Loomba and colleagues performed liver biopsies within 6 months of screening and at week 24. The primary endpoint was fibrosis stage improvement without NASH worsening or NASH improvement without fibrosis worsening. Secondary endpoints included additional histological and noninvasive measures of steatosis, fibrosis and liver injury.

Researchers observed 14.3% of patients in the placebo arm, 30.6% of patients in the PGBF 10 mg arm, 24% of patients in the PGBF 20 mg arm and 26.5% of patients in the PGBF 40 mg arm achieve the primary endpoint at week 24, though statistical significance was not reached (P = .134). While Loomba noted a lack of response across PGBF arms, patient dosed with PGBF experienced larger decreases in liver steatosis and liver stiffness compared with placebo. At week 48, a hepatic fat fraction reduction of greater than or equal to 30% occurred in 8.8%, 21.1%, 20% and 23.1% of patients, respectively, and a liver stiffness reduction of greater than or equal to 15% occurred in 30.3%, 41.2%, 28.6% and 41.2%.

Rohit Loomba
Rohit Loomba

Further evaluation of secondary endpoints yielded decreases in mean PRO-C3, alanine transaminase and aspartate transaminase concentrations as well as increased mean adiponectin concentration compared with placebo. Researchers noted no treatment-related serious adverse events overall.

“Among patients with NASH and stage 3 liver fibrosis, PGBF treatment was safe, generally well tolerated, led to numerically high rates of fibrosis improvement without NASH worsening or NASH improvement without fibrosis worsening,” Loomba concluded. “There were improvements in some histologic as well as some noninvasive markers of steatosis, inflammation and fibrosis demonstrating pharmacologic activity of PGBF in this group of patients but these results were not statistically significant.”