In the Journals

NGM282 improves histological features in NASH by 12 weeks

NGM282 improved the histological features of nonalcoholic steatohepatitis in 12 weeks with significant reductions in nonalcoholic fatty liver disease activity score as well as noninvasive imaging and serum markers, according to a study published in Hepatology.

“NASH now afflicts approximately 6% of the global population. This high burden represents one of our most urgent and most neglected global health crises, with broad impact on public health,” Stephen A. Harrison, MD, medical director of Pinnacle Clinical Research in San Antonio, and colleagues wrote. “Given the continued interest in bile acid and FGF19 biology, our results affirm that modulating the FGF19-FXR axis has great potential as new therapies for liver diseases.”

In a previous randomized control study, 50 patients with NASH received either 1 mg or 3 mg of NGM282 (NGM Biopharmaceuticals) once daily for 12 weeks. In this follow-up evaluation of histological features posttreatment, 43 patients had liver biopsies available from baseline and end of study.

Among patients who received NGM282 1 mg, NAFLD activity score (NAS) improved by 1.9 points (P < .001), fibrosis score decreased by 0.1 point, 92% of patients achieved 5% or more reduction in absolute liver fat content, and 33% achieved completely normalized liver fat content.

In the 3 mg group, NAS improved by 2.3 points (P < .001), fibrosis decreased by 0.5 points (P = .035), 100% of patients achieved 5% or more reduction in absolute liver fat content, and 63% achieved completely normalized liver fat content.

Both the 1 mg group and the 3 mg group demonstrated significant decreases in total bile acids, alanine aminotransferase and aspartate aminotransferase compared with baseline. Circulating levels of C4 also decreased by 76% in the 1 mg group and by 93% in the 3 mg group.

Overall, 50% of those in the 1 mg group and 68% of those in the 3 mg group had a histological response marked by a 2-point or greater improvement in NAS without worsening of fibrosis.

Adverse events were mild to moderate in severity, which was consistent with the previously reported safety profile of NGM282. Four patients experienced serious adverse events that the researchers deemed unrelated to treatment.

“Developing therapeutics for NASH poses a vexing challenge for clinicians and researchers, which requires invasive procedures and lengthy trials,” Harrison and colleagues wrote. “Fibrosis regression is generally presumed to take a long time; however, our results demonstrate that it is possible to shift the needle on fibrosis in a very short period (12 weeks), an observation unprecedented for any therapeutic agents tested in NASH.” – by Talitha Bennett

Disclosure: Harrison reports he has received grants or research support from Allergan, Conatus, Galectin, Galmed, Genfit, Gilead, Immuron, Intercept, Madrigal, Cymabay and TaiwanJ; is on speakers bureau for Alexion and AbbVie; and is a consulting advisor for Allergan, Chronic Liver Disease Foundation, Cymabay, Cirius, Echosens, Genfit, Gilead, Intercept, Madrigal, Novartis, Novo Nordisk, Perspectum, Pippin, CiVi, Hightide, Innovate, PPD, IQVIA, Medpace, and Pfizer. Please see the full study for the other authors’ relevant financial disclosures.

NGM282 improved the histological features of nonalcoholic steatohepatitis in 12 weeks with significant reductions in nonalcoholic fatty liver disease activity score as well as noninvasive imaging and serum markers, according to a study published in Hepatology.

“NASH now afflicts approximately 6% of the global population. This high burden represents one of our most urgent and most neglected global health crises, with broad impact on public health,” Stephen A. Harrison, MD, medical director of Pinnacle Clinical Research in San Antonio, and colleagues wrote. “Given the continued interest in bile acid and FGF19 biology, our results affirm that modulating the FGF19-FXR axis has great potential as new therapies for liver diseases.”

In a previous randomized control study, 50 patients with NASH received either 1 mg or 3 mg of NGM282 (NGM Biopharmaceuticals) once daily for 12 weeks. In this follow-up evaluation of histological features posttreatment, 43 patients had liver biopsies available from baseline and end of study.

Among patients who received NGM282 1 mg, NAFLD activity score (NAS) improved by 1.9 points (P < .001), fibrosis score decreased by 0.1 point, 92% of patients achieved 5% or more reduction in absolute liver fat content, and 33% achieved completely normalized liver fat content.

In the 3 mg group, NAS improved by 2.3 points (P < .001), fibrosis decreased by 0.5 points (P = .035), 100% of patients achieved 5% or more reduction in absolute liver fat content, and 63% achieved completely normalized liver fat content.

Both the 1 mg group and the 3 mg group demonstrated significant decreases in total bile acids, alanine aminotransferase and aspartate aminotransferase compared with baseline. Circulating levels of C4 also decreased by 76% in the 1 mg group and by 93% in the 3 mg group.

Overall, 50% of those in the 1 mg group and 68% of those in the 3 mg group had a histological response marked by a 2-point or greater improvement in NAS without worsening of fibrosis.

Adverse events were mild to moderate in severity, which was consistent with the previously reported safety profile of NGM282. Four patients experienced serious adverse events that the researchers deemed unrelated to treatment.

“Developing therapeutics for NASH poses a vexing challenge for clinicians and researchers, which requires invasive procedures and lengthy trials,” Harrison and colleagues wrote. “Fibrosis regression is generally presumed to take a long time; however, our results demonstrate that it is possible to shift the needle on fibrosis in a very short period (12 weeks), an observation unprecedented for any therapeutic agents tested in NASH.” – by Talitha Bennett

Disclosure: Harrison reports he has received grants or research support from Allergan, Conatus, Galectin, Galmed, Genfit, Gilead, Immuron, Intercept, Madrigal, Cymabay and TaiwanJ; is on speakers bureau for Alexion and AbbVie; and is a consulting advisor for Allergan, Chronic Liver Disease Foundation, Cymabay, Cirius, Echosens, Genfit, Gilead, Intercept, Madrigal, Novartis, Novo Nordisk, Perspectum, Pippin, CiVi, Hightide, Innovate, PPD, IQVIA, Medpace, and Pfizer. Please see the full study for the other authors’ relevant financial disclosures.