Arrowhead Pharmaceuticals has reported early-phase data on a pair of gene silencing drug candidates in obesity, posting preliminary evidence that the molecules help people shed fat to send its stock up.
The update covers one candidate designed to reduce hepatic expression of the INHBE gene and another asset designed to silence adipocyte expression of the ACVR1C gene. Arrowhead shared the most data on its INHBE asset, ARO-INHBE, which it is testing in combination with Eli Lilly’s market-leading GLP-1/GIP receptor agonist tirzepatide.
Four patients with obesity and Type 2 diabetes who received two doses of ARO-INHBE in combination with tirzepatide lost 9.4% of their body weight by Week 16, compared to 4.8% in their counterparts who received placebo with Lilly’s blockbuster. Arrowhead also linked the combination to reductions in visceral fat, total fat and liver fat.
The biotech’s press release lacks data on weight loss in people who took ARO-INHBE as a single agent, although Arrowhead did share monotherapy results for visceral fat, liver fat and lean tissue. Wave Life Sciences recently found the loss of total fat was offset by the gain in lean mass in a phase 1 trial of its rival INHBE candidate, WVE-007, as a monotherapy.
Veru’s talks with the FDA suggest it may be possible to win approval for a molecule that has limited effect on body weight as a single agent. Based on feedback from the FDA, Veru believes showing incremental weight loss when adding a molecule to a GLP-1 drug could serve as a primary endpoint. The FDA’s bar for approval will become a key question as programs focus on shedding fat and sparing muscle advance.
Arrowhead shared the ARO-INHBE data alongside early results on its ACVR1C asset, which is designed to cut ALK7 production. People who received the candidate, ARO-ALK7, had dose-dependent reductions in adipose ALK7 mRNA. The mean reduction on the 200-mg dose hit 88% at Week 8. Arrowhead reported mean, placebo-adjusted visceral fat reduction of 14.1% eight weeks after one dose.
The gaps in Arrowhead’s data, such as the lack of monotherapy weight loss for ARO-INHBE, and the small numbers of patients included in the analyses limit the conclusions that can be reached. Yet with multiple large drugmakers searching for the next big thing in obesity—either to defend their kingdoms or claim a piece of the market—investors are latching on to signs that biotechs could be next to attract dealmakers.
Shares in Arrowhead, a biotech with an $8 billion-plus market cap, rose 17% to $75 per share since market close yesterday.