Positive interim results of human trials for the treatment of NASH: for the first time to reduce the level of key liver proteins

Article source: Medical Rubik's Cube Pro

Author: Li Yuan

On June 23, Arrowhead Pharmaceuticals announced the positive interim results of AROHSD1001 at the EASL International Liver Conference

AROHSD1001 (NCT04202354) is a phase I/II single-dose and multiple-dose escalation study aimed at evaluating RNA interference (RNAi) therapy in normal healthy volunteers and patients with non-alcoholic steatohepatitis (NASH) or suspected NASH patients.

The ARO-HSD developed by Arrowhead consists of a double-stranded RNAi trigger, which is used to selectively target HSD17B13 mRNA in liver cells to reduce the expression of HSD17B13 protein

According to previous studies, HSD17B13 is significantly up-regulated in mouse and human liver cells with non-alcoholic fatty liver disease (NAFLD)

The data released this time proves that ARO-HSD can significantly reduce the mRNA and protein levels of liver HSD17B13, resulting in a decrease in serum alanine aminotransferase (ALT, a marker of liver cell damage)

Pharmacodynamics and efficacy

The amount of liver biopsy performed on day 71 showed that all 5 suspected NASH patients showed strong pharmacodynamic effects

Pharmacodynamic data (Source: Arrowhead)

Decline in ALT in suspected NASH patients (Source: Arrowhead)

Safety and tolerability

ARO-HSD is well tolerated, adverse events are similar between subjects in the ARO-HSD or placebo group, there are no ARO-HSD-related grade 3 or 4 laboratory abnormalities (aboratory abnormalities), no drug-related Serious adverse events

Security data (Source: Arrowhead)

NASH's RNA therapy

The global NASH market has a huge unmet need for treatment.

In the field of RNA therapy at NASH, in addition to Arrowhead, Ionis Pharmaceuticals and Alnylam Pharmaceuticals also have a variety of therapies under development.

Part of the clinical stage of NASH RNA therapy

Source: NextPharma database

Reference materials:

[1] Arrowhead Presents Positive Interim Clinical Data on ARO-HSD Treatment in Patients with Suspected NASH at EASL International Liver Congress (Source: Arrowhead)

[2] Abul-Husn, NS et al.