Arrowhead Presents Positive Interim Clinical Data on ARO-HSD Treatment in Patients with Suspected NASH at EASL International Liver Congress
Arrowhead Pharmaceuticals (NASDAQ: ARWR) announced positive interim results from the Phase 1/2 study of ARO-HSD, an RNA interference therapeutic targeting liver diseases, including nonalcoholic steatohepatitis (NASH). The study showed a mean 84% reduction in hepatic HSD17B13 mRNA and an average 46% decrease in alanine aminotransferase (ALT) levels after just two doses. The treatment was well-tolerated, with no significant safety concerns reported. These findings position ARO-HSD as a promising candidate for later-stage clinical studies, reinforcing HSD17B13's role as a therapeutic target.
- 84% mean reduction in hepatic HSD17B13 mRNA levels in NASH patients.
- 46% average decrease in alanine aminotransferase (ALT) levels post-treatment.
- Well-tolerated with no serious adverse events observed.
- None.
Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today presented positive interim results from AROHSD1001, an ongoing Phase 1/2 clinical study of ARO-HSD, the company’s investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with alcohol-related and nonalcohol related liver diseases, such as nonalcoholic steatohepatitis (NASH), at The International Liver Congress - The Annual Meeting of the European Association for the Study of the Liver (EASL). The data demonstrate that ARO-HSD is the first investigational therapeutic to achieve robust reductions in messenger RNA (mRNA) and protein levels of hepatic HSD17B13, leading to reductions in alanine aminotransferase (ALT), a liver enzyme typically elevated in liver diseases including NASH.
Javier San Martin, M.D., chief medical officer at Arrowhead, said: “Genetic studies have recently shown that HSD17B13 is a compelling target for multiple forms of liver disease. It is exciting to present clinical data at EASL demonstrating that ARO-HSD is the first investigational medicine using any therapeutic modality to achieve inhibition of HSD17B13 in patients. It is also highly encouraging to see ALT levels drop significantly following just two doses of ARO-HSD. These data and the strong genetic evidence of HSD17B13 as a potential therapeutic target provide us with increased confidence as we consider the design of potential late-stage clinical studies for ARO-HSD.”
Pharmacodynamics and Efficacy
All five patients with suspected NASH showed a strong pharmacodynamic effect as measured by liver biopsy at Day 71. HSD17B13 mRNA was reduced by a mean of
Mean ALT reduction from baseline was
Safety and Tolerability
ARO-HSD was well tolerated without any identified safety signals in healthy volunteers given a single dose of ARO-HSD at 25mg, 50mg, 100mg or 200 mg and in the 5 patients with suspected NASH given a single 100 mg dose of ARO-HSD on Days 1 and 29. Adverse events were similar between subjects receiving ARO-HSD or placebo. Two instances of mild injection site bruising and mild injection site erythema were observed in ARO-HSD treated subjects. There were no ARO-HSD associated grade 3 or 4 laboratory abnormalities (NCI-CTCAE v5.0), no drug related serious or severe adverse events, and there were no drug discontinuations.
AROHSD1001 (NCT04202354) is a Phase 1/2 single and multiple dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of ARO-HSD in up to 74 normal healthy volunteers and patients with NASH or suspected NASH. Additional exploratory objectives include the assessment of various measures of drug activity using liver biopsy.
Presentation Details
Title: ARO-HSD reduces hepatic HSD17B13 mRNA expression and protein levels in patients with suspected NASH
Authors: Edward Gane, et al.
Type: Late-Breaking Poster
Date and Time: June 23, 2021 at 8:00 CEST
A copy of the presentation materials may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website. The abstract was also selected for inclusion in The International Liver Congress 2021 Official Scientific Press Conference: NAFLD/NASH on June 25, 2021.
HSD17B13 is a member of the hydroxysteroid dehydrogenase family involved in the metabolism of hormones, fatty acids, and bile acids. Published human genetic data indicate that a loss of function mutation in HSD17B13 provides strong protection against alcoholic hepatitis, cirrhosis, and NASH, with approximately 30
About Arrowhead Pharmaceuticals
Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.
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Source: Arrowhead Pharmaceuticals, Inc.
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1 The New England Journal of Medicine. 2018, 1096-1106
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