Stephen A. Harrison
BOSTON — Patients with non-alcoholic steatohepatitis treated with licogliflozin experienced dose-dependent improvement in alanine aminotransferase levels and other measures, according to study results presented at the Liver Meeting 2019.
Licogliflozin (Novartis) is an inhibitor of sodium-glucose co-transporters 1 and 2 that limits the absorption of glucose from the gut and reabsorption from the kidney.
“Dual inhibition of SGLT1 and SGLT2 with this medication in the gut and kidneys led us to significant weight loss in previous studies and favorable changes in metabolic parameters in patients with type 2 diabetes and/or obesity,” Stephen A. Harrison, MD, medical director of Pinnacle Clinical Research in San Antonio, said in his presentation. “Using that as a backdrop, we wanted to evaluate the efficacy and safety of licogliflozin vs. placebo in patients with NASH over 12 weeks of treatment.”
Researchers conducted a randomized, double-blind, placebo-controlled trial comprising 110 patients with histologically confirmed or phenotypic NASH (defined as BMI 27 kg/m2 in non-Asians or 23 kg/m2 in Asians, ALT 50 in men or 35 in women and type 2 diabetes). They randomly assigned patients to receive either 150 mg or 30 mg of licogliflozin, or placebo for 12 weeks.
The primary outcome of the study was the effect of ALT concentration after 12 weeks. Investigators also assessed the improvement in body weight, liver fat content and aspartate aminotransferase. Seventy-seven patients completed treatment, including 18 who received placebo, 25 who received 30 mg licogliflozin and 34 who received 150 mg licogliflozin.
Patients in the 150 mg and 30 mg groups experienced a 27% and 19% placebo-adjusted reduction in serum ALT concentrations after 12 weeks of treatment, respectively. They also experienced a similar reduction in AST (30% and 23%) and improvement in glutathione S-transferases (32% and 26%).
Patients who received either dose of licogliflozin experienced a placebo-adjusted reduction in body weight of about 4% (P = .0001), and reductions in HbA1c (absolute change: 150 mg, 0.96% [P = .0001]; 30 mg, 0.81% [P = .001]).
Harrison said the drug was generally well-tolerated by patients with the most commonly reported adverse event being diarrhea. A similar number of patients in the 30 mg and placebo groups reported having diarrhea (38.9% vs. 40%), but it was more common in the 150 mg group (76.5%).
“Based on the findings that we’ve seen here, assuming that they hold up through the rest of the trial, it justifies further investigation in long-term studies and in combination with drugs with different mechanisms of action,” Harrison said. “A study called the ELIVATE study will evaluate the drug tropifexor with this medication in combination in patients with NASH and liver fibrosis and will help to define the role in the treatment of NASH.”
Harrison SA, et al. Abstract L07. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.
Disclosures: Harrison reports consulting for 3v Bio, Akero, Altimmune, Axcella, Blade Therapeutics, Chronic Liver Disease Foundation, Cirius, CiVi Biopharma, Contravir, Corcept, Cymabay, Echosens, Foresite, Galmed, Genfit, Gilead, Hightide, HistoIndex, Innovate, Intercept, Madrigal, Medpace, Metacrine, NGM Bio, Novartis, Novo Nordisk, Perspectum, Poxel, Prometic and Viking.