Janssen returns Phase I NASH candidate to Arrowhead

Published: Feb 15, 2023

By Heather McKenzie

BioSpace

J&J’s Janssen Pharmaceutical has given up on an RNAi therapeutic being developed for one of biotech’s hottest targets: non-alcoholic steatohepatitis (NASH). 

Janssen’s development partner, Arrowhead Pharmaceuticals, announced Wednesday it had regained full rights to the candidate, ARO-PNPLA3 (formerly JNJ-75220795).

The therapeutic stemmed from a $3.7 billion collaboration struck between the two companies in 2018. The collaboration was helmed by hepatitis B virus asset ARO-HBV and included the potential for Janssen to select up to three new targets. ARO-PNPLA3 was one of these targets.   

Its Arrowhead given moniker reflects its purpose. Developed on the company’s proprietary TRiM platform, ARO-PNPLA3 is designed to reduce liver expression of patatin-like phospholipase domain containing 3 (PNPLA3), an enzyme encoded by the PNPLA3 gene. 

PNPLA3 has “strong genetic and preclinical validation as a driver of fat accumulation and damage” in the livers of people carrying the I148M mutation, according to Arrowhead.

In a Phase I trial, Arrowhead reported the therapeutic elicited up to 40% mean reduction in liver fat in PNPLA3 I148M homozygotes after a single dose. ARO-PNPLA3 had a solid safety profile, with “mostly mild” adverse events and no patients discontinuing the study due to AEs.

Rohit Loomba, M.D., MHSc, professor of medicine and director of the NAFLD Research Center at University of California at San Diego, called the data “extremely encouraging” and said he looks forward to seeing the molecule progress to a later-stage study. 

In Wednesday’s press release, Christopher Anzalone, Ph.D., president and CEO, Arrowhead, alluded to Janssen’s recently disclosed portfolio overhaul, saying, “We understand that Janssen is undergoing a strategic R&D portfolio review and subsequently advised us” of the decision to return full rights to ARO-PNPLA3.

Janssen’s Strategic Portfolio Review

In an early February town hall meeting, Janssen told employees it was consolidating its vaccines and infectious diseases units and undergoing a “comprehensive review” of its portfolio. This news was first reported by Fierce Pharma.

And on Tuesday, parent company J&J revealed that John Reed would take the helm as executive vice president, pharmaceuticals, R&D. On April 3, Reed will take the reins from William Hait who has served in the role since Mathai Mammen relinquished it in August 2022.