VIENNA — A single dose of NGM313 demonstrated improvements in multiple noninvasive markers of nonalcoholic steatohepatitis, according to a presentation at the International Liver Congress 2019.
“In [a phase 1] study, we demonstrated a very favorable side-effect profile without any significant adverse events,” Alex M. DePaoli, MD, chief medical officer and vice president of translational research at NGM Biopharmaceuticals, said during his presentation. “What we saw in both of these studies was a very acute and significant reduction in triglycerides and this reduction was consistent and at its peak was approximately 50%.”
NGM313 is a once-monthly humanized monoclonal antibody activator of beta-klotho/fibroblast growth factor receptor-1c. In the study presented by DePaoli, researchers compared the effects of a single 240 mg dose of NGM313 with daily Actos (pioglitazone, Takeda Pharmaceuticals) on liver fat content, alanine aminotransferase and aspartate aminotransferase levels, pro-C3, lipids, insulin sensitivity, and safety in patients with NAFLD and insulin resistance.
The study comprised 25 patients randomly assigned to receive NGM313 (n = 17) or 45 mg of pioglitazone (n = 8) for 36 days. Patients had a fasting glucose less than 125 mg/dL, fasting insulin higher than 10 mIU/mL, BMI higher than 30 kg/m2, and liver fat content of 8% or more based on MRI-PDFF.
At day 36, patients who received NGM313 had significant reductions in absolute (–6.3; P < .001) and relative liver fat content (–37%; P < .001), triglycerides (–49 mg/dL; P < .05), HbA1c (–0.22%; P < .001), and ALT (–6.6 IU/L; P < .01), compared with baseline.
Pioglitazone demonstrated similar but less robust reductions in absolute (–4%; P < .01) and relative liver fat content (–25%; P < .01), triglycerides (–38 mg/dL; P < .05) and HbA1c (–0.14%; P < .05), but greater reductions in ALT (–10.5 IU/L; P < .001).
Single dose NGM313 also reduced pro-C3 at a midpoint in the study between day 23 and day 28 (–1.29 ng/mL; P < .05), whereas pioglitazone did not affect pro-C3.
Both drugs demonstrated a favorable safety and tolerability profile with all adverse events considered mild.
“[These effects] were observed as early as 3 weeks and progressed at 5 weeks,” DePaoli concluded. “We anticipate that with persistent dosing that improvements would continue, and we would reach a threshold of 30%, which is thought to be clinically relevant. We believe these data support further work towards the study of NGM313 in NASH.” – by Talitha Bennett
DePaoli AM. Abstract PS-108. Presented at: International Liver Congress; April 10-14, 2019; Vienna, Austria.
Disclosures: DePaoli is chief medical officer and vice president of translational research at NGM Biopharmaceuticals.