Biliary atresia treatment AX-0810 faring well in early testing
Developer says no major issues in healthy volunteers in Phase 1 trial
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AX-0810, an experimental treatment for biliary atresia and primary sclerosing cholangitis (PSC), has so far been well tolerated in early clinical testing.
Initial data from healthy volunteers given a low dose of AX-0810 in a Phase 1 clinical trial showed “no serious adverse events or clinically meaningful laboratory abnormalities,” developer Proqr Therapeutics said in a company press release.
Pharmacological data from the trial have so far been consistent with data from preclinical studies of AX-0810, Proqr said.
“The initial human data from AX-0810 mark an important early milestone for Proqr, providing safety and [pharmacological] observations in healthy volunteers,” said Cristina Lopez Lopez, MD, PhD, the company’s chief medical officer. “These data support continued dosing and position us well for the upcoming target engagement readout in the first half of 2026.”
Proqr said it will provide more information in the coming months. The company also said it is working to modify the Phase 1 trial so that, in addition to healthy volunteers, it will also test AX-0810 in some people with liver disease.
Targeting cholestasis
Biliary atresia and PSC cause cholestasis, a condition in which bile flow is slowed or blocked. Bile is a digestive substance produced by the liver and normally delivered to the intestines via a series of tubes called bile ducts.
Babies with biliary atresia are born with blocked or missing bile ducts, so bile can’t flow properly. In PSC, bile flow is stalled due to inflammation in the bile ducts. In either case, the slowed bile flow causes bile acids, the main component of bile, to build up in liver cells, which can set the stage for liver damage.
AX-0810 is designed to modulate the activity of an RNA molecule in liver cells that contains the instructions for making a protein called NTCP.
NTCP is a transport channel that allows bile acids to enter liver cells. AX-0810 aims to facilitate the production of a modified version of the protein that allows fewer bile acids to enter liver cells, with the ultimate goal of reducing bile buildup and subsequent liver damage.
Some people naturally produce this version of the protein, and these individuals report no symptoms related to bile acid buildup, according to the company.
The ongoing Phase 1 clinical trial is expected to enroll 33 healthy volunteers, who will be randomly assigned to receive increasing doses of AX-0810 (24 participants) or a placebo (nine participants). Treatment will be given via weekly subcutaneous (under-the-skin) injections over four weeks, and participants will then be followed for another 12 weeks.
The main goals of the study are to assess the safety, tolerability, and pharmacological properties of the experimental treatment, and to confirm that it binds its target and works as intended.
Proqr has selected another RNA-targeting therapy, AX-2911, as its lead candidate for metabolic-associated steatohepatitis, a severe form of fatty liver disease in which the buildup of liver fat triggers inflammation and scarring. That therapy has shown promise in preclinical tests, according to the company.
