Arrowhead Pharmaceuticals Emerges as RNAi Powerhouse Amid Sarepta's Challenges

Arrowhead Pharmaceuticals has solidified its position as a leader in RNA interference (RNAi) therapeutics, despite recent market turbulence affecting its partner Sarepta Therapeutics. The company's robust pipeline and strategic partnerships have positioned it as a key player in the pharmaceutical industry, with its first FDA approval on the horizon.

Sarepta Partnership Weathers Storm

Arrowhead's stock price has declined 12% in the past month, caught in the downdraft of Sarepta Therapeutics' gene therapy safety concerns. However, Arrowhead CEO Chris Anzalone remains confident in the partnership, which could be worth up to $11 billion.

"We have been caught in that downdraft as well, unfortunately," Anzalone told BioSpace. "And it's not unreasonable. I think that people were curious about Sarepta's ability to perform on the partnership."

Despite Sarepta's recent challenges, including a third patient death related to its gene therapy, Anzalone believes the partnership remains intact. The deal, signed in November 2024, focuses on rare genetic diseases of the muscle, central nervous system, and lung, with key programs including ARO-DM1 for type 1 myotonic dystrophy and ARO-DUX4 for facioscapulohumeral muscular dystrophy type 1.

Arrowhead has already met one Phase I enrollment target for ARO-DM1, triggering a $100 million milestone payment due by the end of the fourth quarter. Anzalone expects Sarepta to continue performing on the deal, stating, "I would read into that that they're going to spend their last dollar to make sure that [the deal] stays intact, because it's so important for them strategically."

Expanding Pipeline and Commercial Aspirations

Beyond its partnership with Sarepta, Arrowhead is advancing its wholly-owned pipeline, with its lead candidate plozasiran set for an FDA decision on November 18 for familial chylomicronemia syndrome (FCS). This rare genetic metabolic disorder represents Arrowhead's first foray into commercialization.

"We, like any company who goes from an R&D-only organization to R&D plus commercial, are going to make a lot of dumb mistakes," Anzalone admitted. "But it's an ultra-rare indication and [has] allowed us to kind of get our feet wet and learn how to be a commercial organization."

Arrowhead is also targeting the larger severe hypertriglyceridemia indication with plozasiran, currently in Phase III trials expected to complete in mid-2026. Additionally, the company is developing two early-stage obesity assets, including ARO-ALK7, which aims to silence the ACVR1C gene to reduce obesity-related metabolic complications.

"This is the health need of our time in western economies and so the GLP-1s are a very good start, but there's a ton of white space there," Anzalone commented on the obesity market potential.

With partnerships extending beyond Sarepta to include Amgen, GSK, and Takeda, Arrowhead is poised to capitalize on the growing interest in RNAi therapeutics. As the company navigates the transition from a pure R&D organization to a commercial entity, it aims to follow in the footsteps of successful biotechs like Vertex and Regeneron.