Alnylam Announces FDA Approval of AMVUTTRA® (vutrisiran), the First RNAi Therapeutic to Reduce Cardiovascular Death, Hospitalizations and Urgent Heart Failure Visits in Adults with ATTR Amyloidosis with Cardiomyopathy (ATTR-CM)
Alnylam Pharmaceuticals (ALNY) has received FDA approval for AMVUTTRA® (vutrisiran) to treat cardiomyopathy in adults with ATTR amyloidosis (ATTR-CM). The approval expands AMVUTTRA's indication, making it the first therapeutic approved for both ATTR-CM and polyneuropathy of hereditary ATTR amyloidosis.
The approval is based on the HELIOS-B Phase 3 trial results, where AMVUTTRA demonstrated:
- 28% reduction in all-cause mortality and cardiovascular events
- 36% mortality reduction through 42 months
- 33% risk reduction in mortality and cardiovascular events in monotherapy patients
ATTR-CM affects approximately 150,000 people in the U.S. and 300,000 worldwide. AMVUTTRA works by reducing TTR production through RNAi therapy, requiring only four subcutaneous doses annually. The treatment is expected to have broad insurance coverage with most patients paying $0 out-of-pocket costs.
Alnylam Pharmaceuticals (ALNY) ha ricevuto l'approvazione della FDA per AMVUTTRA® (vutrisiran) per il trattamento della cardiomiopatia negli adulti con amiloidosi ATTR (ATTR-CM). L'approvazione amplia l'indicazione di AMVUTTRA, rendendolo il primo terapeutico approvato sia per ATTR-CM che per la polineuropatia dell'amiloidosi ATTR ereditaria.
L'approvazione si basa sui risultati del trial di fase 3 HELIOS-B, dove AMVUTTRA ha dimostrato:
- una riduzione del 28% della mortalità per tutte le cause e degli eventi cardiovascolari
- una riduzione della mortalità del 36% dopo 42 mesi
- una riduzione del 33% del rischio di mortalità e di eventi cardiovascolari nei pazienti in monoterapia
La ATTR-CM colpisce circa 150.000 persone negli Stati Uniti e 300.000 nel mondo. AMVUTTRA agisce riducendo la produzione di TTR attraverso la terapia RNAi, richiedendo solo quattro dosi sottocutanee all'anno. Si prevede che il trattamento avrà una copertura assicurativa ampia, con la maggior parte dei pazienti che non dovrà sostenere costi di tasca.
Alnylam Pharmaceuticals (ALNY) ha recibido la aprobación de la FDA para AMVUTTRA® (vutrisiran) para tratar la cardiomiopatía en adultos con amiloidosis ATTR (ATTR-CM). La aprobación amplía la indicación de AMVUTTRA, convirtiéndolo en el primer tratamiento aprobado tanto para ATTR-CM como para la polineuropatía de la amiloidosis ATTR hereditaria.
La aprobación se basa en los resultados del ensayo de fase 3 HELIOS-B, donde AMVUTTRA demostró:
- una reducción del 28% en la mortalidad por todas las causas y en los eventos cardiovasculares
- una reducción de la mortalidad del 36% a lo largo de 42 meses
- una reducción del 33% en el riesgo de mortalidad y eventos cardiovasculares en pacientes en monoterapia
La ATTR-CM afecta a aproximadamente 150,000 personas en EE. UU. y 300,000 en todo el mundo. AMVUTTRA funciona reduciendo la producción de TTR a través de la terapia de RNAi, requiriendo solo cuatro dosis subcutáneas al año. Se espera que el tratamiento tenga una amplia cobertura de seguro, con la mayoría de los pacientes pagando $0 de costos de bolsillo.
Alnylam Pharmaceuticals (ALNY)는 ATTR 아밀로이드증(ATTR-CM) 성인의 심근병증 치료를 위해 AMVUTTRA® (vutrisiran)에 대한 FDA 승인을 받았습니다. 이 승인은 AMVUTTRA의 적응증을 확장하여 ATTR-CM과 유전성 ATTR 아밀로이드증의 다발신경병증 모두에 대해 승인된 최초의 치료제가 되었습니다.
승인은 HELIOS-B 3상 시험 결과를 기반으로 하며, AMVUTTRA는 다음과 같은 결과를 보여주었습니다:
- 모든 원인에 의한 사망률 및 심혈관 사건에서 28% 감소
- 42개월 동안 36%의 사망률 감소
- 단독요법 환자에서 사망률 및 심혈관 사건의 33% 위험 감소
ATTR-CM은 미국에서 약 150,000명, 전 세계적으로 300,000명에게 영향을 미칩니다. AMVUTTRA는 RNAi 치료를 통해 TTR 생산을 줄임으로써 작용하며, 연간 단 4회의 피하 투여만 필요합니다. 이 치료는 대부분의 환자가 본인 부담 비용이 $0인 폭넓은 보험 적용을 받을 것으로 예상됩니다.
Alnylam Pharmaceuticals (ALNY) a reçu l'approbation de la FDA pour AMVUTTRA® (vutrisiran) afin de traiter la cardiomyopathie chez les adultes atteints d'amyloïdose ATTR (ATTR-CM). Cette approbation élargit l'indication d'AMVUTTRA, en faisant le premier traitement approuvé à la fois pour l'ATTR-CM et la polyneuropathie de l'amyloïdose ATTR héréditaire.
L'approbation est basée sur les résultats de l'
- une réduction de 28 % de la mortalité toutes causes confondues et des événements cardiovasculaires
- une réduction de la mortalité de 36 % sur 42 mois
- une réduction de 33 % du risque de mortalité et d'événements cardiovasculaires chez les patients en monothérapie
L'ATTR-CM touche environ 150 000 personnes aux États-Unis et 300 000 dans le monde. AMVUTTRA agit en réduisant la production de TTR grâce à une thérapie par RNAi, nécessitant seulement quatre doses sous-cutanées par an. On s'attend à ce que le traitement bénéficie d'une large couverture d'assurance, la plupart des patients ne payant aucun frais de leur poche.
Alnylam Pharmaceuticals (ALNY) hat die FDA-Zulassung für AMVUTTRA® (vutrisiran) zur Behandlung von Kardiomyopathie bei Erwachsenen mit ATTR-Amyloidose (ATTR-CM) erhalten. Die Zulassung erweitert die Indikation von AMVUTTRA und macht es zur ersten Therapie, die sowohl für ATTR-CM als auch für die Polyneuropathie der erblichen ATTR-Amyloidose zugelassen ist.
Die Zulassung basiert auf den Ergebnissen der HELIOS-B Phase-3-Studie, in der AMVUTTRA Folgendes zeigte:
- 28%ige Reduktion der Gesamtsterblichkeit und kardiovaskulären Ereignisse
- 36%ige Sterbereduktion über 42 Monate
- 33%ige Risikominderung bei Sterblichkeit und kardiovaskulären Ereignissen bei Monotherapie-Patienten
ATTR-CM betrifft etwa 150.000 Menschen in den USA und 300.000 weltweit. AMVUTTRA wirkt, indem es die TTR-Produktion durch RNAi-Therapie reduziert und erfordert nur vier subkutane Dosen pro Jahr. Es wird erwartet, dass die Behandlung eine breite Versicherungsdeckung hat, wobei die meisten Patienten keine Eigenkosten haben.
- First FDA-approved dual treatment for both ATTR-CM and hATTR-PN
- Significant mortality reduction (36%) through 42 months
- Large addressable market of 150,000 U.S. patients
- Expected broad insurance coverage with $0 out-of-pocket costs for most patients
- Strong efficacy data across all 10 pre-specified trial endpoints
- Treatment only reduces progression but doesn't cure the disease
- Requires ongoing vitamin A supplementation due to decreased serum levels
- Reported adverse reactions including pain in extremity (15%) and arthralgia (11%)
Insights
The FDA approval of AMVUTTRA for ATTR-CM represents a significant commercial expansion for Alnylam that substantially increases the drug's addressable market. This approval transforms AMVUTTRA into a dual-indication therapeutic, making it the first and only treatment approved for both cardiac (ATTR-CM) and neurological (hATTR-PN) manifestations of this disease.
The market opportunity is substantial, with approximately 150,000 potential patients in the US and 300,000 worldwide. Most importantly, the HELIOS-B trial demonstrated compelling efficacy with a 28% reduction in all-cause mortality and cardiovascular events in the overall population, and even stronger results in the monotherapy group with 33% risk reduction. The mortality benefit extended through 42 months with a remarkable 36% reduction - results that position AMVUTTRA favorably against existing treatment options.
From a commercial perspective, Alnylam's established reimbursement infrastructure is critical - they've already achieved 99% insurance coverage for the hATTR-PN indication with most patients paying $0 out-of-pocket. This existing payer framework should accelerate market penetration for the expanded indication. The company's innovative value-based agreements with payers further de-risks the commercial rollout.
The subcutaneous dosing of just four injections annually offers a significant convenience advantage that should drive patient preference and adherence versus more frequently dosed alternatives. With regulatory applications already under review in Europe, Brazil, and Japan, this approval sets the stage for global revenue expansion in 2025-2026.
The clinical significance of AMVUTTRA's approval in ATTR-CM cannot be overstated. This RNAi therapeutic addresses the disease at its source through TTR knockdown, preventing the accumulation of amyloid fibrils that cause irreversible cardiac damage.
What's particularly impressive is the mortality reduction demonstrated in the HELIOS-B trial - a critical endpoint that represents the gold standard in cardiovascular outcomes research. The 36% mortality reduction through 42 months in the overall population and 35% in monotherapy patients demonstrates clear survival benefit. These results were published in the prestigious New England Journal of Medicine, further validating their significance.
From a patient management perspective, AMVUTTRA demonstrated preservation of functional capacity and quality of life metrics while improving key cardiac biomarkers (NT-proBNP and troponin I) that predict cardiovascular outcomes. The safety profile is well-established with over 5,000 patient-years of exposure globally and no new safety concerns identified in the ATTR-CM population.
ATTR-CM has historically been underdiagnosed and undertreated, with most patients experiencing continued disease progression despite existing therapies. Now, cardiologists have a novel mechanistic approach that can potentially halt or slow this progressive disease, addressing both cardiac and neurological manifestations in patients who often present with mixed phenotypes. The convenient dosing schedule of only four subcutaneous injections annually will likely improve adherence compared to daily oral medications, translating to better real-world outcomes.
− Novel Mechanism of Action Delivers Rapid Knockdown of Transthyretin, Addressing the Disease at its Source –
− Proven Consistency of Effect on Cardiovascular Outcomes, Function, and Quality of Life in ATTR-CM Population Representative of Today’s Patients –
– Only Therapeutic Approved in the
– Alnylam Offers Multiple Programs to Support Broad and Seamless Patient Access; Majority of Patients Expected to Pay
– Alnylam to Host Conference Call Today at 6:00 pm ET –
AMVUTTRA® (vutrisiran) product logo
ATTR-CM is a devastating, rapidly progressive, and ultimately fatal disease estimated to affect approximately 150,000 people in the
“The FDA approval of AMVUTTRA for ATTR-CM marks a pivotal advancement for patients, providing a new and clinically differentiated treatment option that has been shown to improve outcomes, including cardiovascular mortality, and reduce progression for those living with this devastating disease,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam. “I would like to extend my deepest gratitude to the patients who participated in our clinical trials, their families and caregivers, the clinical researchers, regulators, and my colleagues at Alnylam who made this approval possible. Today represents a significant milestone in our nearly twenty years of partnership with the ATTR amyloidosis community, but we are not stopping here. We will continue to innovate for patients with ATTR amyloidosis so they can live longer, better, healthier lives.”
AMVUTTRA is an RNAi therapeutic that works upstream to deliver rapid knockdown of TTR, addressing the disease at its source, with only four convenient subcutaneous doses per year. By rapidly knocking down TTR production, AMVUTTRA substantially decreases deposition of TTR fibrils, which form amyloid and cause irreversible cardiovascular damage and premature death in patients with ATTR-CM.
“This FDA approval provides an opportunity to further transform ATTR-CM treatment with a new mechanism of action. The HELIOS-B clinical trial found that vutrisiran allowed patients to live longer, experience fewer hospitalizations, and improve how they function and feel,” said Ronald Witteles, M.D., HELIOS-B Investigator, Professor of Medicine at Stanford University School of Medicine and Co-Director of the Stanford Amyloid Center. “The trial enrolled patients who mirror the real-world population with this disease, and I am very encouraged by vutrisiran’s ability to demonstrate meaningful clinical benefits across both cardiovascular outcomes and multiple measures of disease progression. This is a very exciting day for patients with this challenging disease.”
This approval is based on the HELIOS-B Phase 3 clinical trial which evaluated AMVUTTRA for the treatment of ATTR-CM. The trial achieved statistical significance compared to placebo on all 10 pre-specified primary and secondary endpoints. The results were presented at the European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine. In the overall population, AMVUTTRA reduced the risk of all-cause mortality (ACM) and recurrent cardiovascular (CV) events by
“Despite recent advances, there remains a significant need for patients living with ATTR-CM and I’ve witnessed, firsthand, the impact that ATTR amyloidosis can have on families, including diminished quality of life and the loss of loved ones,” said Muriel Finkel, President of the Amyloidosis Support Groups. “The availability of this groundbreaking treatment option is a significant moment for patients living with ATTR amyloidosis. It represents a beacon of hope for our community.”
AMVUTTRA in hATTR-PN is covered by insurers for ~
Alnylam offers multiple support services and resources for patients prescribed its products through Alnylam Assist®, the only in-house patient support program in ATTR-CM. Alnylam Assist® is designed to provide one-on-one support for patients and their healthcare teams to help navigate the treatment journey, and includes a Quick Start program that provides eligible patients who encounter coverage delays or delays in treatment with an initial dose at no cost. In addition, Alnylam Assist® offers support with insurance coverage, financial assistance, and disease and treatment education for a seamless start to the AMVUTTRA treatment experience. Physicians and patients can learn more about Alnylam’s patient support services by visiting AlnylamAssist.com/amvuttra or calling 1-833-256-2748.
Marketing authorization applications based on HELIOS-B data are currently under review by several global health agencies including the European Medicines Agency (EMA), the Brazilian Health Regulatory Agency (ANVISA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Alnylam remains on track to proceed with additional global regulatory submissions for vutrisiran in 2025.
Visit AMVUTTRA.com/attr-cm for more information.
Investor Webcast Information
Alnylam management will discuss the FDA approval of AMVUTTRA for ATTR-CM via webcast today at 6:00 pm ET. A live audio webcast of the call will be available on the Investors section of the Company’s website at www.alnylam.com/events. An archived webcast will be available on the Company’s website approximately two hours after the event.
INDICATIONS AND IMPORTANT SAFETY INFORMATION
Indications
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 (
In a study of patients with ATTR-CM, no new safety issues were identified.
For additional information about AMVUTTRA, please see the full Prescribing Information.
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
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 with the potential to transform the lives of 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 are ONPATTRO® (patisiran), AMVUTTRA® (vutrisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. 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
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, statements regarding Alnylam’s expectations regarding the safety and efficacy of AMVUTTRA for the treatment of ATTR-CM and hATTR-PN; that FDA approval of AMVUTTRA for ATTR-CM represents a pivotal advancement for patients, providing a new and clinically differentiated treatment option for ATTR-CM; the ability of AMVUTTRA to improve outcomes and reduce progression for patients with ATTR-CM; Alnylam’s ability to continue to innovate for patients with ATTR amyloidosis; the ability of AMVUTTRA or any of Alnylam’s other products or product candidates to enable patients with ATTR amyloidosis to live longer, better and/or healthier lives; the potential for AMVUTRA to transform the treatment of ATTR-CM; the ability of AMVUTTRA to provide ATTR-CM patients with benefits comparable to the clinical benefits observed in the HELIOS-B clinical trial; Alnylam’s expectations that AMVUTTRA in ATTR-CM will have coverage and out-of-pocket cost dynamics similar to AMVUTTRA’s coverage and out-of-pocket cost dynamics in hATTR-PN; and the potential receipt and timing of any future marketing authorizations or the timing of any future regulatory submissions for vutrisiran, 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.
FAQ
What are the key clinical benefits of AMVUTTRA (ALNY) in treating ATTR-CM?
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What is the market size for AMVUTTRA's ATTR-CM indication?
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What makes AMVUTTRA unique in treating ATTR amyloidosis?
