Alnylam to Present Five-Year HELIOS-B Data and Expanding Evidence on the Benefits of RNAi-Powered TTR Silencing with AMVUTTRA® (vutrisiran) at AHA and ISA 2026

– Late-Breaking Presentation at AHA Will Feature Long-Term Results from the HELIOS-B Phase 3 Study, Including Two Years of Open-Label Extension Data in Patients with ATTR-CM –

– HELIOS-B Post Hoc Analysis Demonstrates Positive Impact of AMVUTTRA in Preserving Exercise Capacity and Cardiopulmonary Performance –

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that it will present new clinical and real-world data at the American Heart Association (AHA) Scientific Sessions 2026, taking place November 6-9 in Chicago, Illinois, and the International Symposium on Amyloidosis (ISA) 2026, taking place November 15-18 in Montevideo, Uruguay. The presentations add to the growing body of evidence demonstrating strength in RNAi-powered transthyretin (TTR) silencing with AMVUTTRA^® (vutrisiran), including long-term cardiovascular outcomes and functional measures, while providing new insights into the multisystemic manifestations of transthyretin-mediated amyloidosis (ATTR) and opportunities for earlier diagnosis and treatment.

“Alnylam continues to pioneer TTR silencing through RNAi innovation, with an expanding evidence base that reinforces the potential of AMVUTTRA to transform ATTR care,” said Yvonne Greenstreet, M.D., Chief Executive Officer of Alnylam. “The landmark HELIOS-B study established a strong foundation for AMVUTTRA, and the research being presented at AHA and ISA reflects our determination to build on this progress and drive the next chapter in the treatment of this progressive disease.”

A highlight of the AHA program will be a late-breaking presentation of five-year results from the HELIOS-B Phase 3 study, including two years of open-label extension data evaluating long-term outcomes with vutrisiran in patients with the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM). The findings will provide additional insights into the long-term clinical effects of RNAi-powered TTR silencing, including outcomes among patients receiving continuous vutrisiran treatment and those who initially received placebo before switching to vutrisiran.

A second late-breaking presentation of cardiopulmonary exercise testing (CPET) with imaging of 48 patients enrolled in HELIOS-B will show that treatment with vutrisiran preserved exercise capacity and cardiopulmonary performance during exercise over two years compared with placebo, providing mechanistic insight into the functional benefits of TTR silencing in ATTR-CM. An additional real-world evidence analysis of sex-related differences in ATTR may inform efforts to improve earlier diagnosis.

At ISA, a post hoc analysis of HELIOS-B will highlight statistically significant benefits of vutrisiran versus placebo on neuropathy-related quality-of-life measures among patients with ATTR-CM and evidence of polyneuropathy, further strengthening the body of data supporting TTR silencing across the multisystemic manifestations of ATTR amyloidosis in both hereditary and wild-type ATTR. Separately, real-world data from more than 1,000 patients initiating vutrisiran will demonstrate a higher prevalence of heart failure and greater comorbidity burden among second-line versus first-line initiators, supporting the rationale for initiating vutrisiran earlier in the treatment pathway. In addition, results from an indirect treatment comparison of vutrisiran versus acoramidis in ATTR-CM will be presented.

The AHA Scientific Sessions 2026 regular / non-late breaking abstracts are available here and ISA 2026 abstracts are available here. Alnylam will make the data presentations available on its Capella site.

AHA Scientific Sessions 2026 Presentation Details

ISA 2026 Presentation Details

AMVUTTRA^® (vutrisiran) INDICATIONS AND IMPORTANT SAFETY INFORMATION

Indications Approved by the U.S. FDA

AMVUTTRA^® (vutrisiran) is indicated for the treatment of the:

• cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits.
• polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults.

Important Safety Information

Reduced Serum Vitamin A Levels and Recommended Supplementation

AMVUTTRA treatment leads to a decrease in serum vitamin A levels.

Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).

Adverse Reactions

In a study of patients with hATTR-PN, the most common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%).

In a study of patients with ATTR-CM, no new safety issues were identified.

For additional information about AMVUTTRA, please see the full U.S. Prescribing Information (revised March 2025)

The therapeutic indications described above are those approved by the U.S. FDA. AMVUTTRA is not currently registered in Uruguay.

About AMVUTTRA^® (vutrisiran)

AMVUTTRA^® (vutrisiran) demonstrates strength in RNAi-powered transthyretin (TTR) silencing, delivering rapid knockdown of TTR at the source of disease to address the underlying cause of transthyretin amyloidosis (ATTR). As ATTR is a rapidly progressive disease, even when patients may appear clinically stable, early treatment intervention is critical. In the HELIOS-B Phase 3 study, AMVUTTRA reduced the risk of all-cause mortality and recurrent CV events compared to placebo in the overall and monotherapy populations by 28.2% and 32.8%, respectively, through 36 months. It is the only TTR silencer approved for both the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) and cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in countries globally. More than 14,000 patients worldwide have been treated with AMVUTTRA, which is recommended by the European Society of Cardiology as a Class I, Level A treatment for patients with ATTR-CM. AMVUTTRA is administered once every three months via subcutaneous injection.

About Transthyretin Amyloidosis (ATTR)

Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by pathogenic transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart, and gastrointestinal tract. Patients may present with polyneuropathy, cardiomyopathy, or both manifestations of disease. There are two different forms of ATTR – hereditary ATTR (hATTR), which is caused by a TTR gene variant, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant. It is estimated that more than 500,000 people worldwide live with ATTR, with ~80% remaining undiagnosed.

About RNAi Technology

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam Pharmaceuticals

Alnylam (Nasdaq: ALNY) is a leading global biopharmaceutical company and the pioneer of the RNA interference (RNAi) revolution. The Company is focused on developing transformative therapies with the potential to prevent, halt, or reverse disease. For more than two decades, Alnylam has advanced the Nobel-Prize-winning science of RNAi, delivering critical breakthroughs and six approved medicines. Alnylam has medicines available in more than 70 countries and a rapidly expanding and robust pipeline, in addition to consistently being recognized as an exceptional workplace and socially responsible organization. The Company is executing on its Alnylam 2030 strategy to accelerate innovation and scale impact to transform human health. For more information, please visit www.alnylam.com or follow Alnylam on X, LinkedIn, Facebook, Instagram, or YouTube.

Alnylam Forward-Looking Statements

This press release contains forward-looking statements. Forward-looking statements include statements regarding Alnylam’s expectations, beliefs, goals, plans or prospects, including, without limitation, statements regarding: Alnylam’s ability to pioneer TTR silencing through RNAi innovation; the potential of AMVUTTRA to transform ATTR care; Alnylam’s ability to build on its progress and drive the next chapter in the treatment of ATTR; the potential for the real-world evidence analysis of sex-related differences in ATTR to inform efforts to improve earlier diagnosis; and Alnylam’s ability to achieve the goals in its Alnylam 2030 strategy. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to: Alnylam’s ability to successfully execute on its Alnylam 2030 strategy; Alnylam’s ability to successfully launch, market and sell Alnylam’s approved products globally, including AMVUTTRA; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; delays, interruptions or failures in the manufacture and supply of Alnylam’s marketed products or its product candidates; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products; the outcome of litigation and government investigations; the risk of future litigation and government investigations; and unexpected expenditures; as well as those risks and uncertainties more fully discussed in the “Risk Factors” filed with Alnylam’s most recent periodic report (Quarterly Report on Form10-Q or Annual Report on Form 10-K) filed with the SEC and in its other SEC filings. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

Alnylam Pharmaceuticals, Inc.

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(Media)
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(Investors)
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