Alnylam Submits Regulatory Application to the European Medicines Agency for Vutrisiran for the Treatment of ATTR Amyloidosis with Cardiomyopathy
Alnylam Pharmaceuticals (Nasdaq: ALNY) has submitted a Type II Variation to the European Medicines Agency (EMA) for vutrisiran, an investigational RNAi therapeutic for treating ATTR amyloidosis with cardiomyopathy (ATTR-CM). This submission is based on positive results from the HELIOS-B Phase 3 study, which met all 10 primary and secondary endpoints with statistical significance.
The study demonstrated vutrisiran's effects on reducing mortality and cardiovascular events, as well as improving functional capacity, quality of life, and heart failure symptoms in ATTR-CM patients. Vutrisiran's safety profile was consistent with its established profile for hATTR amyloidosis with polyneuropathy.
Alnylam has also submitted a supplemental New Drug Application (sNDA) to the U.S. FDA for vutrisiran in ATTR-CM treatment, with additional global regulatory submissions planned.
Alnylam Pharmaceuticals (Nasdaq: ALNY) ha presentato una Variazione di Tipo II all'Agenzia Europea dei Medicinali (EMA) per vutrisiran, una terapia sperimentale RNAi per il trattamento dell'amiloidosi ATTR con cardiomiopatia (ATTR-CM). Questa presentazione è basata sui risultati positivi dello studio HELIOS-B di fase 3, che ha raggiunto tutti e 10 gli endpoint primari e secondari con significatività statistica.
Lo studio ha dimostrato gli effetti di vutrisiran sul ridurre la mortalità e gli eventi cardiovascolari, oltre a migliorare la capacità funzionale, la qualità della vita e i sintomi di insufficienza cardiaca nei pazienti con ATTR-CM. Il profilo di sicurezza di vutrisiran è stato coerente con il profilo già stabilito per l'amiloidosi hATTR con polineuropatia.
Alnylam ha anche presentato una domanda supplementare di Nuovo Farmaco (sNDA) all'FDA degli Stati Uniti per vutrisiran nel trattamento dell'ATTR-CM, con ulteriori presentazioni normative globali pianificate.
Alnylam Pharmaceuticals (Nasdaq: ALNY) ha presentado una Variación de Tipo II a la Agencia Europea de Medicamentos (EMA) para vutrisiran, una terapia experimental de RNAi para el tratamiento de la amiloidosis ATTR con cardiomiopatía (ATTR-CM). Esta presentación se basa en los resultados positivos del estudio HELIOS-B de fase 3, que cumplió con los 10 objetivos primarios y secundarios con significación estadística.
El estudio demostró los efectos de vutrisiran en reducir la mortalidad y los eventos cardiovasculares, así como en mejorar la capacidad funcional, la calidad de vida y los síntomas de insuficiencia cardíaca en pacientes con ATTR-CM. El perfil de seguridad de vutrisiran fue coherente con su perfil establecido para la amiloidosis hATTR con polineuropatía.
Alnylam también ha presentado una Solicitud Suplementaria de Nuevo Medicamento (sNDA) a la FDA de EE. UU. para vutrisiran en el tratamiento de ATTR-CM, con más presentaciones regulatorias globales planificadas.
알니람 제약 (Nasdaq: ALNY)은 ATTR 심근병증 (ATTR-CM) 치료를 위한 실험적인 RNAi 치료제인 부트리시란에 대해 유럽 의약품청(EMA)에 II형 변동 신청을 제출했습니다. 이번 제출은 HELIOS-B 3상 연구의 긍정적인 결과를 기반으로 하며, 이는 10개의 주요 및 보조 목표를 통계적으로 유의미하게 충족했습니다.
이 연구는 ATTR-CM 환자에서 부트리시란이 사망률과 심혈관 사건을 줄이는 데 미치는 영향과 기능적 능력, 삶의 질 및 심부전 증상을 개선하는 효과를 입증했습니다. 부트리시란의 안전성 프로필은 다발신경병을 동반한 hATTR 아밀로이드증에 대한 기존 프로필과 일치했습니다.
알니람은 ATTR-CM 치료를 위한 부트리시란에 대해 미국 FDA에 추가적인 신규 의약품 보충 신청(sNDA)을 제출했으며, 추가적인 글로벌 규제 제출이 계획되어 있습니다.
Alnylam Pharmaceuticals (Nasdaq: ALNY) a soumis une Variation de Type II à l'Agence Européenne des Médicaments (EMA) pour vutrisiran, un thérapeutique RNAi expérimental pour le traitement de l'amiloïdose ATTR avec cardiomyopathie (ATTR-CM). Cette soumission est basée sur des résultats positifs de la étude HELIOS-B de phase 3, qui a atteint tous les 10 objectifs primaires et secondaires avec une signification statistique.
L'étude a démontré les effets de vutrisiran sur la réduction de la mortalité et des événements cardiovasculaires, ainsi que sur l'amélioration de la capacité fonctionnelle, de la qualité de vie et des symptômes d'insuffisance cardiaque chez les patients atteints d'ATTR-CM. Le profil de sécurité de vutrisiran était conforme à son profil établi pour l'amiloïdose hATTR avec polyneuropathie.
Alnylam a également soumis une Demande de Nouveau Médicament Supplémentaire (sNDA) à la FDA des États-Unis pour vutrisiran dans le traitement de l'ATTR-CM, avec d'autres soumissions réglementaires mondiales prévues.
Alnylam Pharmaceuticals (Nasdaq: ALNY) hat eine Typ-II-Abänderung bei der Europäischen Arzneimittel-Agentur (EMA) für vutrisiran, ein experimentelles RNAi-Therapeutikum zur Behandlung der ATTR-Amyloidose mit Kardiomyopathie (ATTR-CM), eingereicht. Diese Einreichung basiert auf positiven Ergebnissen der HELIOS-B Phase-3-Studie, die alle 10 primären und sekundären Endpunkte mit statistischer Signifikanz erfüllte.
Die Studie zeigte die Auswirkungen von vutrisiran auf die Reduzierung der Sterblichkeit und kardiovaskulären Ereignisse sowie die Verbesserung der Funktionsfähigkeit, Lebensqualität und Symptome von Herzinsuffizienz bei ATTR-CM-Patienten. Das Sicherheitsprofil von vutrisiran entsprach dem etablierten Profil für hATTR-Amyloidose mit Polyneuropathie.
Alnylam hat außerdem einen ergänzenden New Drug Application (sNDA) bei der US-FDA für vutrisiran zur Behandlung von ATTR-CM eingereicht, mit weiteren globalen behördlichen Einreichungen, die geplant sind.
- Vutrisiran met all 10 primary and secondary endpoints in the HELIOS-B Phase 3 study
- Vutrisiran demonstrated significant reduction in all-cause mortality and cardiovascular events
- Vutrisiran improved functional capacity, quality of life, and heart failure symptoms in ATTR-CM patients
- Safety profile of vutrisiran in HELIOS-B was consistent with its established profile for hATTR amyloidosis
- Vutrisiran treatment leads to a decrease in serum vitamin A levels, requiring supplementation
Insights
The submission of a Type II Variation to the EMA for vutrisiran in ATTR amyloidosis with cardiomyopathy (ATTR-CM) is a significant development. This application is based on the positive HELIOS-B Phase 3 study results, which demonstrated substantial reductions in all-cause mortality and cardiovascular events. The study met all 10 primary and secondary endpoints with statistical significance, showcasing vutrisiran's potential efficacy in treating this life-threatening condition.
Key points to consider:
- Vutrisiran's mechanism of action involves rapidly reducing TTR levels, addressing the root cause of ATTR-CM.
- The safety profile in HELIOS-B was consistent with its established profile in hATTR amyloidosis with polyneuropathy.
- The drug showed improvements in functional capacity, quality of life and heart failure symptoms.
This regulatory submission could potentially expand vutrisiran's indications, offering a new treatment option for ATTR-CM patients. The positive study results and the drug's novel RNAi approach position it as a promising therapy in this underserved market.
Alnylam's regulatory submission for vutrisiran in ATTR-CM represents a significant potential market expansion. With a current market cap of
- Expanded market opportunity: ATTR-CM affects a larger patient population than hATTR amyloidosis with polyneuropathy, potentially increasing vutrisiran's addressable market.
- First-mover advantage: If approved, vutrisiran could become one of the first RNAi therapeutics for ATTR-CM, potentially capturing significant market share.
- Diversified revenue: Approval would further diversify Alnylam's product portfolio, reducing reliance on existing therapies.
Investors should monitor the regulatory process closely, as approval could drive significant growth. However, it's important to consider potential competition and pricing pressures in the evolving ATTR-CM market landscape.
− Type II Variation Submission Based on the Positive HELIOS-B Phase 3 Study in which Vutrisiran Significantly Reduced the Risk of Death and Cardiovascular Events Relative to Placebo –
“Today marks another important milestone in our journey to bring RNAi therapeutics to patients with high unmet need around the world,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “ATTR-CM is a rapidly progressive, debilitating, and life-threatening disease that is an increasingly recognized cause of heart failure. Vutrisiran rapidly knocks down TTR, and in the HELIOS-B study treatment with vutrisiran substantially reduced all-cause mortality and cardiovascular events, underscoring the potential of this therapy for those living with the disease. We look forward to working closely with the EMA with the aim to bring this new treatment option to patients as soon as possible.”
The regulatory application is based on positive results from the pivotal HELIOS-B Phase 3, randomized, double-blind, placebo-controlled multicenter global study which met all 10 of its primary and secondary endpoints across both the overall and monotherapy populations, each with statistical significance. The findings demonstrated the effects of vutrisiran on outcomes of mortality and cardiovascular events, as well as functional capacity (6-minute walk test), quality of life (Kansas City Cardiomyopathy Questionnaire), and heart failure symptoms and severity (NYHA class) in patients with ATTR-CM. The safety profile of vutrisiran in HELIOS-B was consistent with the established profile of the drug for hATTR amyloidosis in adult patients with polyneuropathy. In HELIOS-B, rates of adverse events (AEs), serious AEs, severe AEs and AEs leading to study drug discontinuation were similar between the vutrisiran and placebo arms. Detailed results from the HELIOS-B study were published in The New England Journal of Medicine.
A supplemental New Drug Application (sNDA) for vutrisiran has been submitted to the
AMVUTTRA® (vutrisiran) INDICATION AND IMPORTANT SAFETY INFORMATION
Indication
In
Important Safety Information
Reduced Serum Vitamin A Levels and Recommended Supplementation
Vutrisiran treatment leads to a decrease in serum vitamin A levels. Supplementation of approximately, but not exceeding, 2500 IU to 3000 IU vitamin A per day is advised for patients taking vutrisiran. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).
Adverse Reactions
The most frequently occurring adverse reactions in patients treated with vutrisiran were pain in extremity and arthralgia. Other commonly reported adverse reactions with vutrisiran were dyspnoea, injection site reaction and increase in blood alkaline phosphatase.
For additional information about vutrisiran, please see the full Summary of Product Characteristics.
About AMVUTTRA® (vutrisiran)
AMVUTTRA® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of variant and wild‑type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, vutrisiran is approved and marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Vutrisiran is also in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM), which encompasses both wild-type and hereditary forms of the disease.
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.5 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.6 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.5 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) 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 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, Alnylam’s expectations regarding the safety and efficacy of vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy and the potential of vutrisiran to improve outcomes for patients with ATTR amyloidosis with cardiomyopathy; the potential for vutrisiran to obtain regulatory approval for the treatment of ATTR amyloidosis with cardiomyopathy, in the EU or elsewhere, and the timing of any such regulatory approval(s) 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” strategy; Alnylam’s ability to successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates, including vutrisiran; actions or advice of regulatory agencies and Alnylam’s ability to obtain regulatory approval for its product candidates, including vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; and any delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2023 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 its other SEC filings. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its 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.
5 Elbashir SM, Harborth J, Lendeckel W, et al. Nature. 2001;411(6836):494-498.
6 Zamore P. Cell. 2006;127(5):1083-1086.
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Alnylam Pharmaceuticals, Inc.
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(Investors and Media)
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(Investors)
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Source: Alnylam Pharmaceuticals, Inc.
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