Alnylam Highlights AMVUTTRA Momentum, Resets 2026 TTR Revenue Outlook

Key Points

• AMVUTTRA continues to gain momentum in TTR cardiomyopathy, supported by HELIOS-B data, quarterly dosing, patient access initiatives and physician adoption. Alnylam said its TTR franchise exceeded $1 billion in second-quarter revenue.
• Alnylam lowered its 2026 TTR franchise revenue outlook to $4.2 billion–$4.5 billion, citing a shift toward the broader market mix of approximately 80% first-line and 20% second-line use. The company still sees substantial growth potential because most TTR cardiomyopathy patients remain undiagnosed and untreated.
• The company expects several pipeline catalysts, including October Phase I data for its Huntington’s disease program, proof-of-concept obesity data, continued development of bleeding-disorder treatment ALN-6400, and progress on the TRITON-CM study of nucresiran.

Alnylam Pharmaceuticals NASDAQ: ALNY highlighted continued momentum for its AMVUTTRA treatment in transthyretin-mediated cardiomyopathy, while outlining a pipeline of upcoming clinical catalysts and discussing changes in the market that prompted a revision to its 2026 TTR franchise revenue outlook.

Speaking at the Morgan Stanley Global Healthcare Conference, Chief Executive Officer Yvonne Greenstreet said Alnylam’s TTR franchise generated more than $1 billion in revenue during the second quarter. The company received its cardiomyopathy indication for AMVUTTRA in March 2025.

Greenstreet attributed the launch performance to data from the HELIOS-B study, access initiatives and physician adoption. She said the study produced results on all-cause mortality across patient subgroups, including patients using stabilizers and those not receiving stabilizers. Alnylam has also continued to generate analyses of cardiac structure and function and extracardiac manifestations, she said.

AMVUTTRA’s quarterly subcutaneous dosing also supports adherence, Greenstreet said. She added that most patients can obtain the drug with no out-of-pocket cost, while 90% can access treatment within 10 miles of home. Alnylam has more than 50% market share among physicians who have used AMVUTTRA, according to Greenstreet.

Guidance Reset Reflects Second-Line Demand

Alnylam revised its 2026 TTR franchise revenue guidance to a range of $4.2 billion to $4.5 billion, representing a $200 million reduction at the midpoint. Greenstreet said the revision reflected a better understanding of how second-line demand has evolved.

At the 2025 launch, the company saw pent-up demand from patients who were progressing on existing treatments and awaiting a new option. The company’s business was then approximately balanced between first-line and second-line use. In 2026, that mix has moved toward what Greenstreet described as the broader market’s composition: roughly 80% first-line and 20% second-line.

Despite the revised outlook, Greenstreet said market fundamentals remain strong. She cited an estimated 200,000 TTR cardiomyopathy patients in the U.S. and 500,000 globally, with approximately 80% of patients still undiagnosed and untreated.

John Kennedy, senior vice president of global commercialization and lead of the TTR franchise, said Alnylam expects modest, gradual net-price reductions over time as volume and experience build. On a proposed change involving the 340B program, Kennedy said the outcome remains uncertain following the comment period, though historically proposed rule changes are generally concluded in November.

Kennedy said Alnylam has developed alternate sites of care to preserve patient access and offer providers options. Greenstreet said the company’s priority is ensuring patients who need AMVUTTRA can obtain it.

Company Sees HELIOS-B as Distinct From CARDIO-TTRansform

Greenstreet addressed questions surrounding results from the CARDIO-TTRansform study of eplontersen, saying the trial’s outcome reflected several factors, including the degree of TTR knockdown, enrolled patient population and endpoint selection.

She noted that eplontersen achieved less than 70% mean TTR knockdown in that study, compared with 81% mean knockdown for AMVUTTRA in HELIOS-B. Greenstreet said the difference was meaningful and suggested the collective evidence could indicate a relationship between deeper TTR knockdown and better outcomes in TTR cardiomyopathy.

She also pointed to the importance of treating patients earlier in their disease course and using endpoints that capture the multisystem nature of TTR cardiomyopathy. Kennedy said a survey of cardiologists conducted after the initial announcement of the CARDIO-TTRansform outcome found that physicians overwhelmingly did not expect to change their current behavior or their view of silencing therapies.

Alnylam is continuing enrollment in its TRITON-CM study of nucresiran, which Greenstreet said has shown 95% TTR knockdown. The company is considering whether changes to patient enrollment, including potential enrichment or a larger study, may be appropriate. If it makes enrollment-related changes, Alnylam would disclose them before year-end, she said. Changes to the statistical analysis plan could be made later in the study.

Greenstreet also said Alnylam now expects generic tafamidis to become available in 2031 rather than 2028. She said that timing should reduce near-term pricing pressure and give AMVUTTRA more time to become established as a foundational therapy.

Pipeline Catalysts Ahead

Greenstreet identified several pipeline programs expected to produce updates later in the year. Alnylam plans to report Phase I data in October for its Huntington’s disease program, which is designed to address both full-length huntingtin and the exon 1 fragment. The company expects to assess safety, tolerability, pharmacokinetics and pharmacodynamics, including huntingtin lowering in cerebrospinal fluid.

The company is also advancing ALN-6400, a plasminogen-targeting program for bleeding disorders. A Phase II study in hereditary hemorrhagic telangiectasia is evaluating bleeding frequency and severity in patients who may experience severe nosebleeds, gastrointestinal bleeding, anemia and transfusion requirements. Alnylam is also developing the program in von Willebrand disease.

In obesity, Greenstreet said Alnylam expects proof-of-concept data later this year aimed at demonstrating delivery of siRNA into adipose tissue. The company is evaluating potential obesity applications as monotherapy and in combinations with other siRNA medicines or incretin therapies.

For zilebesiran, Alnylam is conducting a large outcomes study in hypertension. Greenstreet said the company believes infrequent subcutaneous dosing could support more continuous blood-pressure control and address medication adherence challenges.

Finally, Greenstreet said Alnylam is using artificial intelligence across its operations and has entered an agreement with Inceptive Nucleics to combine the partner’s frontier models with Alnylam’s siRNA data in an effort to accelerate innovation.

About Alnylam Pharmaceuticals (NASDAQ:ALNY)

Alnylam Pharmaceuticals, Inc is a biopharmaceutical company focused on discovering, developing and commercializing medicines based on RNA interference (RNAi) technology. RNAi therapies are designed to silence specific genes involved in disease, offering a way to target conditions that may be difficult to treat with conventional drug approaches. The company was founded in 2002 and is headquartered in Cambridge, Massachusetts.

Alnylam's commercial products include Onpattro (patisiran), Givlaari (givosiran), Oxlumo (lumasiran) and Amvuttra (vutrisiran).

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