Arrowhead heralded the results as proof of concept that inhibiting the Activin E pathway can improve body composition and enhance weight loss as compared to tirzepatide alone, particularly in patients with type 2 diabetes.
Arrowhead Pharma’s drug doubled the weight loss achieved with Eli Lilly’s tirzepatide alone, while quickly reducing types of fat that are considered key drivers of metabolic disease in an early-stage trial. The results sent the company’s shares up 17%, as Arrowhead makes its obesity debut.
The interim results come from a small group of patients in two Phase I/IIa trials, featuring Arrowhead’s RNAi therapeutics ARO-INHBE and ARO-ALK7. The former reduced weight by 9.4% at week 16 in four patients with type 2 diabetes when combined with Eli Lilly’s tirzepatide, according to a Tuesday press release. Arrowhead said this result represents a doubling of the weight loss that tirzepatide achieved alone. Lilly’s drug achieved 4.8% weight loss at week 16 in five patients who did not receive Arrowhead’s therapy. ARO-INHBE tripled the reduction of visceral fat, total fat and liver fat compared to the mega-blockbuster as well. These results come from just three patients.
Tested without tirzepatide, ARO-INHBE reduced visceral fat by 9.9%, liver fat by 38% and increased total lean tissue by 3.6%. This group had placebo-adjusted mean visceral fat reduction of 15.6% at week 24.
Arrowhead heralded the results as proof of concept that inhibiting the Activin E pathway can improve body composition and enhance weight loss as compared to tirzepatide alone, particularly in patients with type 2 diabetes.
The company’s shares spiked 17% to $75.20 apiece as the markets opened Tuesday.
Truist Securities, reflecting on the results’ implications for Lilly in a Tuesday morning note, called the weight loss achieved by Arrowhead’s drug “substantial” and “meaningful.” The firm said that interest in weight loss quality has waned recently as the market looks to the launch of oral options from Lilly and Novo Nordisk. But Arrowhead’s results could reignite that conversation. Key opinion leaders in metabolic disease remain concerned about the long-term impact of weight loss without more targeted therapies, according to Truist.
Other therapies trying to address weight loss composition include Scholar Rock’s apitegromab, Lilly’s bimagrumab and Wave Life Sciences’ WVE-007, according to Truist.
As for safety, Arrowhead said treatment-emergent adverse events were mild in severity and there were none that led to discontinuations. There was one report of limb abscess, which was treated with drainage and considered unrelated to the treatment. Gastrointestinal side effects were similar in the combo and tirzepatide-alone groups and there were no “clinically significant” elevations of liver enzymes, glycemic indices or lipid parameters revealed on lab tests, according to the release.
Arrowhead also revealed initial data for ARO-ALK7, which showed gene target silencing—the first such drug to do so, according to the company. The therapy reduced adipose ALK7 mRNA by 88% at week eight. The therapy also spurred a placebo-adjusted 14.1% reduction in visceral fat. It was well tolerated, Arrowhead said.
Arrowhead CEO Chris Anzalone told BioSpace last year that he is most excited about ARO-ALK7. The drug is meant to silence the ACVR1C gene, in turn reducing the risk of obesity-related metabolic complications. The company plans to keep both programs in-house, while many others are subject to major partnerships with the likes of Sarepta Therapeutics and Novartis.
The Phase I/IIa trials for ARO-INHBE and ARO-ALK7 are continuing and Arrowhead expects to have more results later this year. The company will host a conference call at 11:30 a.m. ET today.
Arrowhead secured its first ever approval in November 2025, with an FDA nod for plozasiran, now known as Redemplo, for patients with familial chylomicronemia syndrome.
Arrowhead’s results could be a boon for Lilly, which is awaiting a key approval of the oral weight loss drug orforglipron, according to Truist. Sales of ARO-INHBE could bolster tirzepatide given the combination approach tested in this early-stage trial. Arrowhead’s option is also injectable, meaning it won’t compete directly with orforglipron. Lilly could launch that drug as early as March, if the FDA gives the green light.
