PXL065 proves safe, well-tolerated ahead of phase 2 trial for NASH

Poxel announced positive safety, tolerability and pharmacokinetic results from a phase 1b multiple ascending dose trial of PXL065, a deuterium-stabilized R-stereoisomer of Actos under investigation for nonalcoholic steatohepatitis, according to a press release.

“NASH is a major public health concern and is a growing contributor to the burden of end-stage liver disease. There remains an urgent need to develop effective therapeutics for NASH,” Arun Sanyal, MD, from the Virginia Commonwealth University School of Medicine, said in the release. “[Actos] has been shown in multiple studies to improve NASH with a trend for improvement in hepatic fibrosis. However, its use is limited by its side effects, especially weight gain. PXL065 is an exciting innovation with the potential to preserve the beneficial effects of pioglitazone on NASH while limiting the associated side effects.”

The randomized control phase 1b trial comprised 30 healthy participants who received three ascending doses of PXL065 (7.5 mg, 15 mg, and 30 mg) over 7 days compared with Actos (pioglitazone, Takeda Pharmaceuticals) 45 mg.

PXL065 plasma exposure increased in a dose-proportional manner up to 30 mg and stabilization of R-pioglitazone with deuterium occurred in all dose groups.

Poxel also announced plans to initiate a phase 2 trial in patients with NASH without cirrhosis for 36 weeks, following feedback from the FDA. The phase 2 trial will include the same ascending dose groups compared with placebo in at least 120 patients, taking place in the second quarter of 2020.

The primary endpoint of the phase 2 trial will be reduction of liver fat mass measured by MRI proton density fat fraction.

“With these results, combined with other clinical and preclinical data, we are able to identify the dosing range of 7.5 mg to 22.5 mg that will be evaluated in the phase 2 trial, a range we believe has the potential to provide an improved therapeutic profile over 45 mg [pioglitazone],” Thomas Kuhn, CEO of Poxel, said in the release.

Reference: www.poxelpharma.com