Amvuttra Approved as First RNAi Silencer for Rare Cardiomyopathy

The FDA's recent approval of Alnylam's Amvuttra introduces a new contender in the treatment landscape for transthyretin amyloid cardiomyopathy (ATTR-CM), setting the stage for heightened competition with existing treatments from Pfizer and BridgeBio. This approval marks a significant development, as Amvuttra is the first RNA interference (RNAi) therapeutic specifically targeting ATTR-CM, a condition characterized by abnormal transthyretin protein deposits in the heart, leading to impaired cardiac function.

Previously, Pfizer's tafamidis, marketed as Vyndaqel and Vyndamax, was the first drug approved for this rare condition in 2019. BridgeBio followed suit with its transthyretin stabilizer, Attruby, receiving FDA approval in November 2024. In contrast, Amvuttra employs a novel mechanism by silencing both wildtype and mutant transthyretin RNA, thereby reducing the expression of the problematic TTR protein. Alnylam is optimistic that this unique approach will provide a distinct advantage over existing therapies, offering improved patient outcomes.

Alnylam CEO Yvonne Greenstreet emphasized the significance of Amvuttra's approval, highlighting its potential to improve cardiovascular mortality rates and slow disease progression—critical considerations for those affected by this debilitating condition. This approval for ATTR-CM is Amvuttra's second FDA endorsement, having previously been authorized for treating polyneuropathy associated with hereditary transthyretin-mediated (hATTR) amyloidosis.

The competitive landscape for ATTR-CM therapies is undergoing rapid expansion, with each company vying for market share in a sector projected to reach $11.2 billion by 2030. Pfizer's tafamidis initially paved the way in 2019, and BridgeBio's Attruby joined the fray in 2024. Alnylam's entry with Amvuttra is anticipated to further intensify competition, especially since the drug offers a different treatment paradigm by addressing both wildtype and mutant transthyretin RNA forms.

Tolga Tanguler, Alnylam's chief commercial officer, expressed confidence in Amvuttra’s competitive edge, citing its rapid knockdown of TTR protein levels as a key differentiator. This therapeutic strategy addresses the disease at its source, providing a potentially more effective treatment option. Analysts are keenly observing how much market share Amvuttra can capture, especially in light of its anticipated approval for ATTR-CM.

The administration and pricing of Amvuttra may significantly influence its competitive positioning. Unlike Attruby, which requires daily oral administration, Amvuttra is administered in four subcutaneous doses annually. Although the pricing for the new indication remains undisclosed, in the ATTR-PN domain, Amvuttra was priced nearly double compared to Attruby and tafamidis. This pricing strategy could impact patient and prescriber decisions, particularly given Amvuttra's Medicare Part B coverage, which minimizes out-of-pocket costs for patients compared to the Part D coverage of its competitors.

With a strong foundation in the ATTR-PN market, Alnylam is poised to leverage its experience and infrastructure to ensure Amvuttra’s success in ATTR-CM. The company's existing RNAi therapeutic, Onpattro, has demonstrated commercial success, contributing significantly to Alnylam’s revenue in previous years. Amvuttra aims to be a first-line treatment choice, supported by data from Alnylam's HELIOS-B study, which showed a notable reduction in mortality risk across all causes.

The evolving ATTR-CM space also includes potential future contenders. AstraZeneca and Ionis are developing another RNA silencer, while Intellia is working on a gene-editing approach that promises a one-time treatment option, potentially reducing the treatment burden on patients.

Alnylam continues to push forward, developing a third-generation RNAi therapeutic, nucresiran, which promises deeper and faster TTR protein knockdown. This candidate is expected to begin Phase III trials soon. Given the increasing prevalence of ATTR-CM and the substantial unmet need, continued innovation in this field is essential, as emphasized by Alnylam leadership.