Lyon, France-based Poxel's Phase II DESTINY-1 trial in non-alcoholic steatohepatitis (NASH) hit its primary efficacy endpoint of liver fat decrease at 36 weeks.
Poxel presented the positive histology data in a Wednesday morning conference call. Thomas Kuhn, Poxel's CEO, said in the call that the company was "thrilled" by the Phase II NASH results, and that "these data were really consistent with initial results."
NASH is a metabolic disease that can lead to liver cirrhosis but is not associated with alcohol intake. It is related to an accumulation of fat in the liver that causes inflammation and scarring (fibrosis). It is linked to the obesity epidemic, type 2 diabetes and elevated cholesterol and triglycerides.
In the trial, 117 participants received one of four doses per day. Investigators conducted liver biopsies to analyze histological changes before and after the 36-week treatment period.
They observed improvements in fibrosis by >1 stage without NASH getting worse, an endpoint, the company indicates, the FDA recognizes for approval. This was seen in 31-50% of patients receiving the drug compared to 17% receiving placebo. In all PXL065 cohorts total, 39% saw improvement in fibrosis by 1 stage or greater without worsening NASH compared to 17% in the placebo group.
The primary efficacy endpoint was a statistically significant mean relative decrease compared to placebo in liver fat content from baseline to 36 weeks. This was observed in all patients receiving the drug at all doses. In patients receiving the 22.5mg dose, 40% of patients hit a >30% relative decrease in liver fat content.
As a result of the data, Kuhn stated in the conference call, that "PXL065 will be prioritized for further development in NASH." The company expects to initiate talks with regulatory authorities on its drug's pivotal Phase III program.
Poxel's PXL065 is a deuterium-stabilized R-stereoisomer of pioglitazone, which is approved to treat type 2 diabetes.
Latest Developments in NASH
NASH has been a difficult for the biopharma industry. GlobalData forecasted that the NASH market will reach $18.3 billion by 2026, but to date, no specific drugs have been approved to treat NASH. Typically, treatments are lifestyle changes, such as diet and exercise, Vitamin E and pioglitazone have been used.
Still, a few companies have announced progress recently in NASH. In September, Akero Therapeutics reported that its efruxifermin (EFX) improved liver fibrosis and prevented NASH from worsening in pre-cirrhotic NASH patients. It demonstrated statistical significance on primary and secondary histology endpoints at 24 weeks in the Phase IIb HARMONY trial at two doses, 28mg and 50mg.
A day later, Oramed announced positive Phase II data of ORMD-0801 in type 2 diabetes patients with NASH. The drug decreased liver fat content based on histology endpoints at 12 weeks. ORMD-0801 is a form of oral insulin.
In mid-September, Alnylam Pharmaceuticals and Regeneron Pharmaceuticals announced preliminary Phase I data of ALN-HSE, an investigational RNAi treatment for NASH. In healthy volunteers, the drug appeared safe and was "associated with robust target knockdown and numerically lower liver enzymes and biopsy-derived non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) over six months."
Studies for NASH by Gilead and GenFit failed in late-stage trials, and one of the more promising drugs, Intercept Pharmaceuticals' obeticholic acid (OCA), was rejected by the FDA for NASH in 2020. However, the company announced positive data from a Phase III REGENERATE trial in July and plans to resubmit its New Drug Application.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.