An Early Signal of Promise in Gene Silencing for Obesity
While all eyes in obesity focused on the launch of a daily oral tablet for ongoing treatment, Arrowhead Pharmaceuticals brought us a little surprise yesterday. They presented early data from phase one studies of two gene silencing therapies for obesity. Though these data are quite preliminary, they offer a signal of great promise for a totally different approach to treating obesity.
Two Different RNAi Therapies
In a webinar update, Arrowhead presented data from phase 1/2a studies for two potential gene silencing therapies. These are early studies in relatively small numbers of persons with obesity. These two therapies each target a different gene. They work by a mechanism known as RNA interference to block the expression of the target gene. Thus, they are called RNAi therapies.
One of these therapies, ARO-INHBE, targets the INHBE gene in the liver. By doing that it reduces secretion of Activin E by that gene. Activn E regulates metabolism in fat tissue.
The other of these therapies is called ARO-ALK7. So it targets the ALK7 gene in fat tissue. Animal studies suggest that targeting this gene might reduce fat mass while preserving lean muscle.
Both of these drugs offer the potential for infrequent dosing – perhaps once every three months.
Promising Results
First, let’s be clear. These are early, interim results. The company is presenting them before any peer review and the numbers of patients is small. That’s how it is with a phase one study. The real goal is to understand safety and guide decisions about dosing.
But nonetheless, these therapies appear to have had impressive effects on patients. For instance, in combination with tirzepatide, ARO-INHBE almost doubled the loss of fat compared with the outcome for tirzepatide alone. Both of these drugs appear to have favorable effects on their own, while also having an acceptable safety profile.
Independent researcher Carol le Roux commented on these results, saying:
“The interim clinical trial results announced today for Arrowhead’s ARO-INHBE and ARO-ALK7 show dramatic and rapid reductions in visceral fat, a key driver in metabolic diseases. Furthermore, ARO-INHBE in combination with tirzepatide almost doubled weight loss and improved multiple measures of body composition versus tirzepatide alone in patients with obesity and type 2 diabetes mellitus. This is promising and demonstrates therapeutic potential for RNAi-based targeting of the Activin E/ALK7 pathway directly in a patient population that typically loses less weight on therapy and experiences worse cardiovascular outcomes compared to non-diabetic patients. This is a clear area of high unmet need.”
Many Questions Remain
Yes, these are tantalizing data. But we have many questions. What will the full results tell us and how will they hold up in peer review? What will this drug look like in larger study populations? How will this add to what we can do to improve the health of persons living with obesity?
Answers will come with time and we will be watching closely.
Click here for the company announcement of these results, here for the slides presented on them, and here for the webinar. For further reporting, click here, here, and here.
Silence, painting by Odilon Redon / WikiArt
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January 7, 2026
