Company Announcements

− New Data Follow Recent U.S. FDA Approval of AMVUTTRA^® (vutrisiran) as First RNAi Therapeutic to Reduce Cardiovascular Death, Cardiovascular Hospitalizations and Urgent Heart Failure Visits in Patients with ATTR-CM –

− Vutrisiran Favorably Impacted Echocardiographic Systolic and Diastolic Function –

− Vutrisiran Treatment Led to Maintenance or Improvement in Functional Capacity, Health Status, and Quality of Life, Compared to Placebo –

− Benefits of Vutrisiran Observed Across Baseline Heart Failure Severities, with Greatest Benefit in Patients with Early Disease –

− Findings Published in JACC −

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Mar. 29, 2025-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced moderated poster presentations of new data from the landmark HELIOS-B Phase 3 clinical trial, which evaluated vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM) in a population representative of today’s patients. Data were presented at the American College of Cardiology’s Annual Scientific Session (ACC.25) held in Chicago, Illinois. These data build upon the body of clinical evidence which supported the recent U.S. Food and Drug Administration (FDA) approval of AMVUTTRA^® (vutrisiran) for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits. AMVUTTRA is an RNAi therapeutic that works upstream to deliver rapid knockdown of transthyretin, addressing the disease at its source, with four subcutaneous doses per year.

“The HELIOS-B study continues to deliver a robust data package showcasing the unique, differentiated value of vutrisiran as a first-line treatment option that can enable patients with ATTR-CM to live longer, better, and healthier lives,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “Data showing beneficial effects on cardiac systolic and diastolic function are novel and indicate the direct impact of vutrisiran in cardiac structure and function of patients living with ATTR-CM. These findings, together with the observed improvements in functional capacity, health status and quality of life, as well as the reductions in all-cause mortality and cardiovascular events, demonstrate the rapid, broad, and sustained impacts of vutrisiran on ATTR-CM and underscore the importance of early intervention for this progressive and ultimately fatal disease.”

Moderated Poster Presentations:

The Relationship Between Cardiac Structure, Function, and Clinical Outcomes and the Impact of Vutrisiran from the HELIOS-B Trial

New echocardiographic data from the HELIOS-B Phase 3 clinical trial, the largest systematic echocardiographic study in a pivotal trial, demonstrated that treatment with vutrisiran improved echocardiographic cardiac function. Vutrisiran treatment led to significant improvements in diastolic function and attenuation of declines in left ventricular (LV) and right ventricular (RV) systolic function at Month 18, compared to placebo. Baseline measures of LV and RV systolic function, as well as indices of diastolic function, were shown to provide important prognostic information beyond clinical characteristics and biomarker-based staging systems. Notably, worsening LV and RV systolic function over 18 months was significantly associated with an increased risk of subsequent all-cause death, highlighting the importance of these parameters in assessing disease progression. The improved clinical outcomes of patients receiving vutrisiran in HELIOS-B may be mediated by its impact on cardiac function.

Impact of Baseline Heart Failure Severity on Efficacy of Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy in the HELIOS-B Trial: A Subgroup Analysis

An exploratory subgroup analysis demonstrated that vutrisiran reduced all-cause mortality and recurrent cardiovascular events across a range of baseline heart failure severities in patients with ATTR-CM. The greatest benefit was observed in patients with earlier, less severe disease, underscoring the need for timely diagnosis and early intervention. Similar effects were seen in the monotherapy population and across additional endpoints, including functional capacity and cardiac biomarkers, reinforcing the efficacy of vutrisiran regardless of disease stage. These results were recently published in JACC.

Maintenance or Improvement of Functional Capacity, Health Status, and Quality of Life with Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy: Data from the HELIOS-B Study

A separate analysis confirmed that vutrisiran significantly maintained or improved functional capacity, and patient-reported health status and quality of life, compared to placebo over 30 months. Greater proportions of patients treated with vutrisiran preserved or improved 6-minute walk test distance and Kansas City Cardiomyopathy Questionnaire scores at clinically meaningful thresholds. These findings provide further evidence of vutrisiran’s ability to deliver meaningful benefits beyond reducing mortality and cardiovascular events. These results were recently published in JACC.

An additional Flatboard Poster presentation, “Real-World Persistency on Tafamidis: An Analysis of U.S. Insurance Claims Data” will be presented on Monday, March 31 at 10:30 am (CDT), 11:30 am (EDT).

To view the results presented at ACC.25, please visit Capella.

About AMVUTTRA^® (vutrisiran)

AMVUTTRA^® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection by a healthcare professional, AMVUTTRA is approved and marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults and is approved in the U.S. 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. For more information about AMVUTTRA, including the full U.S. Prescribing Information, visit AMVUTTRA.com.

About ATTR

Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating and fatal disease caused by misfolded 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 affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant and impacts an estimated 200,000 – 300,000 people worldwide.^1-4

About RNAi

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 Pharmaceuticals (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines for people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products include ONPATTRO^® (patisiran), AMVUTTRA^® (vutrisiran), GIVLAARI^® (givosiran), and OXLUMO^® (lumasiran), which are being developed and commercialized by Alnylam, and Leqvio^® (inclisiran) and Qfitlia^™ (fitusiran), which are being developed and commercialized by Alnylam’s partners, Novartis and Sanofi, respectively. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P⁵x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on X (formerly Twitter) at @Alnylam, or on LinkedIn, Facebook, or Instagram.

Alnylam Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, Alnylam’s expectations regarding the safety and efficacy of vutrisiran for the treatment of ATTR-CM, including the ability of vutrisiran to reduce mortality and cardiovascular events in ATTR-CM patients; the potential of vutrisiran to become a first-line therapy for ATTR-CM; the potential of vutrisiran to enable ATTR-CM patients to live longer, better and healthier lives; and the potential for early treatment with vutrisiran to have beneficial effects in ATTR-CM patients should be considered forward-looking statements.

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 P⁵x25” goals; 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; successfully launching, marketing and selling Alnylam’s approved products globally; delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future; 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; the potential risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2024 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q, and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing Alnylam’s views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

¹ Hawkins PN, Ando Y, Dispenzeri A, et al. Ann Med. 2015;47(8):625-638.
² Gertz MA. Am J Manag Care. 2017;23(7):S107-S112.
³ Conceicao I, Gonzalez-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21:5-9.
⁴ Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013;8:31.

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Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom
(Investors and Media)
+1-617-682-4340

Josh Brodsky
(Investors)
+1-617-551-8276

Source: Alnylam Pharmaceuticals, Inc.