SAN FRANCISCO—89bio, Inc. has closed the enrollment in its Phase 1b/2a trial for nonalcoholic steatohepatitis (NASH), with 98% of patients enrolled. 89bio also reported new preclinical data confirming BIO89-100’s mechanism of action via potent FGF receptor agonism, but it’s not all good news for the company — it has also delayed initiation of its severe hypertriglyceridemia (SHTG) trial due to the COVID-19 pandemic.
The Phase 1b/2a proof-of-concept trial in NASH is a multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose-ranging trial in patients with NASH, or with NAFLD and a high risk of NASH. 81 patients have been randomized to receive weekly or every other week subcutaneous dosing of either BIO89-100 or placebo for 12 weeks.
The trial is designed to assess the safety, tolerability and pharmacokinetic properties of BIO89-100, as well as absolute change from baseline in hepatic fat fraction measured by magnetic resonance imaging — proton density fat fraction (MRI-PDFF). MRI-PDFF will be assessed at week 7 and at the end of the trial, along with other key biomarkers that will be evaluated more frequently.
“I am extremely proud that our team was able to close enrollment in our Phase 1b/2a NASH trial with 98% of patients enrolled, despite the challenging environment related to the ongoing COVID-19 pandemic,” said Rohan Palekar, chief executive officer of 89bio. “We are monitoring the situation and will adjust plans if needed to minimize any trial disruption due to COVID-19. We continue to expect topline data in the second half of 2020. In the interim, we plan to complete all preparatory work to enable enrollment as soon as conditions enable it.”
89bio says that the company is working closely with its contract research organization partners and clinical sites to mitigate any potential impact of the COVID-19 pandemic on the trial. 89bio plans to initiate the Phase 2b trial in the first half of 2021. But 89bio is delaying the initiation of its Phase 2 trial of BIO89-100 for the treatment of SHTG, which was planned for the first half of 2020. 89bio plans to complete all activities required to be operationally prepared to enroll the SHTG trial, once the company can execute the trial safely and effectively.
In an in vitro study of receptor agonism, BIO89-100 was shown to have activity at very low nanomolar concentrations in cells co-expressing β-klotho and each of FGF receptors 1c, 2c or 3c. The EC50 (concentration at which one half of the maximal FGF receptor agonist effect is observed) for BIO89-100 was similar across FGF receptors 1c, 2c and 3c, and comparable or superior to that of rhFGF21 in this functional assay.
“Our new preclinical data demonstrates that BIO89-100 has similar activity to rhFGF21 at FGF receptors 1c, 2c and 3c, suggesting that BIO89-100 could reproduce the beneficial metabolic benefits of the native hormone, which may translate into clinical benefits for patients with NASH and SHTG,” explained Dr. Hank Mansbach, chief medical officer of 89bio.