Aruniram has big ambitions for Amvutra. However, despite the launch of explosive transthyretin amyloid cardiomyopathy (ATTR-CM) in 2025, three questions remain: potential future competition from AstraZeneca and Ionis’ rival silencer Wainua, genericization of market-leading Pfizer’s tafamidis, and opportunities for the overall ATTR-CM market.
Addressing these questions, Alnylam management on Tuesday outlined a path for Amvuttra to become the revenue leader in the vast ATTR-CM field, where more than 75,000 U.S. patients are treated by 2030, with data, diagnostics, marketing campaigns and physician experience providing clues to fuel future growth in siRNA therapies.
Alnylam’s confidence is rooted in Amvuttra’s accomplishments to date, marking the one-year anniversary of physician approval of ATTR-CM.
As the third market entrant, Amvuttra had captured 35% new brand market share at the end of 2025, just three quarters after its launch.
“This clearly demonstrates the unmet need and willingness of both physicians and patients to adopt new treatment approaches,” Tolga Tangler, Alnylam’s chief commercial officer, said on an investor call Tuesday.
Future competition from Wainua
Amvuttra is currently the only ATTR silencer in the ATTR-CM space, but AZ and Ionis are preparing to challenge Alnylam’s position with their own product, the Wainua. Phase 3 data from the Cardio-TTRansform trial is expected to be released this year, and Wainua could differentiate itself by potentially incorporating tafamidis into its indications.
However, John Kennedy, Alnylam’s global commercialization lead for the TTR franchise, insisted that the alternative silencer was a “net positive” for the category.
That’s because “the majority of cardiologists believe that the favorable combination therapy data supports a broader class effect,” he explained on a conference call.
Although Amvuttra’s current FDA indication does not specifically specify its use in combination with tafamidis, the Phase 3 Helios B study supporting ATTR-CM’s use demonstrated therapeutic efficacy regardless of whether Alnylam’s drug was used with background tafamidis. Therefore, a positive combination readout from Cardio-TTRansform would confirm the findings from Helios-B and also strengthen the case for the Amvuttra combination, Kennedy said.
The two drugs are already at odds in another form of ATTR, hereditary ATTR polyneuropathy (ATTR-PN), with Amvuttra maintaining about 70% of new treatments in this category and more than 80% of total market share.
“We think all of these dynamics also impact cardiomyopathy,” Kennedy said.
Regarding potential changes in pricing and access dynamics, Kennedy again pointed to the current ATTR-PN competition, which is led by Amvuttra. Additionally, Amvuttra has strong access with 90% coverage in first-line ATTR-CM treatment while competing with cheaper oral stabilizers, proving that “calculus does not change when mixed with another pharmacy benefit drug,” he added.
Addressing the potential threat posed by Generic Tafamidis
While the expected loss of exclusivity (LOE) for Pfizer’s Vindamax franchise in late 2028 is often seen as a threat to the branded therapy, Alnylam’s leadership categorizes it as a potential catalyst for growth.
First, Amvuttra is already establishing itself as a first-choice option among physicians. Tangler said that doctors who have tried Amvtra are increasingly using the injection as a first-line treatment for new patients. This is very important because as doctors gain experience, they will expand its use to more patients.
Mark Soud, Alnylam’s head of US and head of TTR, said this preference built ahead of Tafamidis’ LOE “positions us well for sustained growth over the long term.”
Mr. Soued argued that genericization would not create a universal step-editing requirement that would be detrimental to Amvuttra’s reimbursement.
“It’s also important to remember that in Medicare piecework, which is our single largest payer segment and accounts for about half of our business today, Amvuttra has label-to-label coverage with no step-up redactions, and we expect that dynamic to continue following the Tafamidis LOE,” he said.
However, the executive did not rule out the possibility of a step-edit policy, especially in commercial markets. Nevertheless, he pointed out that even with today’s step edits, patients can access Amvuttra either through appeal or progression from stabilizers.
Alnylam sees the Tafamidis Cliffs as a potential growth opportunity rather than a threat. According to the company, the availability of generic stabilizers could significantly reduce the cost of combinations with silencers.
“Cardiologists are already used to adding and combining treatments for cardiovascular disease; this is how they practice,” Soud says.
Again, data from AZ and Ionis rivals could increase the credibility of the combined approach. Alnylam is also gathering real-world evidence through its DemonsTTRate observational study, and the company expects to analyze data across competitions and combinations.
Calculating numbers on ATTR-CM market potential
Amvuttra and BridgeBio’s stabilizer Attruby achieved explosive growth rates in 2025, but declining revenues for Pfizer’s Vyndamax in the US have sparked debate about the ultimate size of the ATTR-CM market.
Soud suggested that the entire ATTR-CM category is still in its infancy based on market patterns for other diseases such as pulmonary arterial hypertension and atrial fibrillation. “As recognition, screening practices, clinical guidelines, and treatment landscapes all evolve, the diagnosis rate for these new diseases could eventually reach around 70%,” he said.
Currently, about 80% of the estimated 200,000 ATTR-CM patients in the United States remain untreated, Soud said. This patient pool already exceeds the 125,000 patients Alnylam served in October 2024.
Tangler pointed out that only Pfizer was able to increase the ATTR-CM treatment population by 56% annually in 2023 and 2024. This growth rate will accelerate to 77% in 2025, suggesting that new treatment options are contributing to the overall market expansion.
Additionally, Alnylam estimates that approximately 15,000 patients are receiving treatment for the first time annually, an increase from the company’s previous calculations of approximately 10,000. Additionally, approximately half of patients appear to have progressive disease after receiving stabilizers, representing another target population for Amvtra.
To maintain this momentum, Alnylam is investing in awareness campaigns and new technologies that enable earlier diagnosis and better coordinated care for patients.
The first pillar of Alnylam’s strategy is direct-to-consumer advertising, and the company takes a highly customized approach.
“Our target audience is seeing it, and it’s working,” Kennedy said. “Already today, we are the most requested ATTR-CM therapy by patients.”
To identify patients earlier in the disease process, Alnylam just announced a partnership with Viz.ai. Through a prospective implementation study, the companies will integrate electronic health records and AI algorithms across five large U.S. health systems to help clinicians identify patients early and assist in diagnosis confirmation and referral.
Additionally, a three-year initiative between the Massachusetts biotech and the American Heart Association will convene 10 institutions to identify the “ideal care model” for patients with ATTR-CM, Kennedy said.
With all of these efforts in place, Alnylam has the potential to treat more than 75,000 patients with ATTR-CM in the U.S. by 2030, Tangler said. “It will be a competitive market, but Amvuttra stands out among it and is poised to become the TTR revenue leader by 2030.”
