Alnylam Submits Supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration for Vutrisiran for the Treatment of Transthyretin Amyloidosis with Cardiomyopathy
Alnylam Pharmaceuticals (Nasdaq: ALNY) has submitted a supplemental New Drug Application (sNDA) to the FDA for vutrisiran, an investigational RNAi therapeutic for treating ATTR amyloidosis with cardiomyopathy (ATTR-CM). The submission is based on positive results from the HELIOS-B Phase 3 study, which demonstrated favorable effects on outcomes of death and cardiovascular events, functional capacity, and quality of life in ATTR-CM patients.
Alnylam utilized a Priority Review Voucher to accelerate the FDA review timeline. Vutrisiran, currently approved as AMVUTTRA® for treating polyneuropathy of hereditary ATTR amyloidosis in adults, showed a safety profile consistent with its established profile in the HELIOS-B study. The company believes vutrisiran has the potential to become a first-line therapy for ATTR-CM, pending regulatory approval.
Alnylam Pharmaceuticals (Nasdaq: ALNY) ha presentato una richiesta supplementare per un nuovo farmaco (sNDA) alla FDA per vutrisiran, un terapeutico investigativo RNAi per il trattamento dell'amiloidosi ATTR con cardiomiopatia (ATTR-CM). La richiesta si basa su risultati positivi dello studio di Fase 3 HELIOS-B, che hanno dimostrato effetti favorevoli sugli esiti di morte ed eventi cardiovascolari, capacità funzionale e qualità della vita nei pazienti con ATTR-CM.
Alnylam ha utilizzato un Voucher per Revisioni Prioritarie per accelerare i tempi di revisione della FDA. Vutrisiran, attualmente approvato come AMVUTTRA® per il trattamento della polineuropatia da amiloidosi ATTR ereditaria negli adulti, ha mostrato un profilo di sicurezza coerente con quello già stabilito nello studio HELIOS-B. L'azienda ritiene che vutrisiran abbia il potenziale per diventare una terapia di prima linea per l'ATTR-CM, in attesa dell'approvazione regolatoria.
Alnylam Pharmaceuticals (Nasdaq: ALNY) ha presentado una solicitud suplementaria de nuevo medicamento (sNDA) a la FDA para vutrisiran, un terapéutico investigacional de RNAi para el tratamiento de amiloidosis ATTR con cardiomiopatía (ATTR-CM). La presentación se basa en resultados positivos del estudio de Fase 3 HELIOS-B, que demostró efectos favorables sobre los resultados de muerte y eventos cardiovasculares, capacidad funcional y calidad de vida en pacientes con ATTR-CM.
Alnylam utilizó un Vale de Revisión Prioritaria para acelerar el cronograma de revisión de la FDA. Vutrisiran, actualmente aprobado como AMVUTTRA® para el tratamiento de la polineuropatía de la amiloidosis ATTR hereditaria en adultos, mostró un perfil de seguridad consistente con su perfil ya establecido en el estudio HELIOS-B. La empresa cree que vutrisiran tiene el potencial de convertirse en una terapia de primera línea para ATTR-CM, a la espera de la aprobación regulatoria.
Alnylam Pharmaceuticals (Nasdaq: ALNY)는 ATTR 심근병증 (ATTR-CM) 치료를 위한 연구용 RNAi 치료제인 vutrisiran의 FDA에 대한 추가 신약 신청(sNDA)을 제출했습니다. 이 제출은 ATTR-CM 환자의 사망 및 심혈관 사건, 기능적 능력 및 삶의 질에 대한 긍정적인 영향을 입증한 HELIOS-B 3상 연구의 긍정적인 결과를 기반으로 합니다.
Alnylam은 FDA 검토 일정을 가속화하기 위해 우선 검토 바우처를 사용했습니다. 현재 성인의 유전성 ATTR 아밀로이드증의 말초 신경병증 치료를 위해 AMVUTTRA®로 승인된 vutrisiran은 HELIOS-B 연구에서 입증된 안전성 프로필과 일치하는 안전성 프로필을 보여주었습니다. 이 회사는 vutrisiran이 규제 승인이 이루어지면 ATTR-CM에 대한 일차 요법이 될 잠재력이 있다고 믿고 있습니다.
Alnylam Pharmaceuticals (Nasdaq: ALNY) a soumis une demande de nouveau médicament complémentaire (sNDA) à la FDA pour vutrisiran, un traitement thérapeutique à base d'ARNi en essai pour traiter l'amiloïdose ATTR avec cardiomyopathie (ATTR-CM). Cette soumission est basée sur des résultats positifs de l'
Alnylam a utilisé un Bon de Révision Prioritaire pour accélérer le calendrier de révision de la FDA. Vutrisiran, actuellement approuvé sous le nom d'AMVUTTRA® pour le traitement de la polynévropathie de l'amiloïdose ATTR héréditaire chez les adultes, a montré un profil de sécurité conforme à son profil établi dans l'étude HELIOS-B. L'entreprise croit que vutrisiran a le potentiel de devenir une thérapie de première intention pour l'ATTR-CM, en attente de l'approbation réglementaire.
Alnylam Pharmaceuticals (Nasdaq: ALNY) hat einen ergänzenden Antrag auf Zulassung eines neuen Arzneimittels (sNDA) bei der FDA für vutrisiran eingereicht, eine experimentelle RNAi-Therapie zur Behandlung von ATTR-Amyloidose mit Kardiomyopathie (ATTR-CM). Der Antrag basiert auf positiven Ergebnissen aus der HELIOS-B Phase 3-Studie, die günstige Auswirkungen auf Sterblichkeits- und kardiovaskuläre Ereignisse, Funktionsfähigkeit und Lebensqualität bei ATTR-CM-Patienten zeigte.
Alnylam nutzte einen Prioritätsprüfungs-Gutschein, um den Prüfungszeitraum der FDA zu beschleunigen. Vutrisiran, das derzeit als AMVUTTRA® zur Behandlung der hereditären ATTR-Amyloidose bei Erwachsenen genehmigt ist, zeigte ein Sicherheitsprofil, das mit dem in der HELIOS-B-Studie etablierten Profil übereinstimmt. Das Unternehmen glaubt, dass vutrisiran das Potenzial hat, eine Erstlinientherapie für ATTR-CM zu werden, vorbehaltlich der behördlichen Genehmigung.
- Submission of sNDA to FDA for vutrisiran in ATTR-CM treatment
- Positive results from HELIOS-B Phase 3 study showing favorable effects on patient outcomes
- Use of Priority Review Voucher to accelerate FDA review timeline
- Potential for vutrisiran to become first-line therapy for ATTR-CM
- None.
Insights
The submission of an sNDA for vutrisiran to treat ATTR amyloidosis with cardiomyopathy (ATTR-CM) is a significant regulatory milestone for Alnylam. Key points:
- Use of a Priority Review Voucher accelerates the FDA review timeline, potentially expediting market access.
- The application is based on positive Phase 3 HELIOS-B study results, demonstrating efficacy in reducing mortality and cardiovascular events.
- Vutrisiran's safety profile in HELIOS-B aligns with its established profile, which is important for regulatory approval.
- If approved, vutrisiran could become a first-line therapy for ATTR-CM, expanding its current indication for polyneuropathy in hereditary ATTR amyloidosis.
This submission positions Alnylam to potentially capture a larger share of the ATTR amyloidosis market, pending FDA approval. The accelerated review process could give Alnylam a competitive advantage in bringing this treatment to ATTR-CM patients quickly.
This sNDA submission for vutrisiran in ATTR-CM represents a significant market opportunity for Alnylam:
- ATTR-CM is a fatal disease with treatment options, indicating a high unmet medical need and potential for strong market demand.
- Positive HELIOS-B results, showing improvements in mortality and cardiovascular events, position vutrisiran as a potentially competitive therapy in this space.
- The
$34.8 billion market cap of Alnylam (ALNY) could see substantial growth if vutrisiran gains approval for this expanded indication. - Vutrisiran's subcutaneous administration every three months offers a convenient dosing schedule, which could drive patient preference and market adoption.
Investors should monitor the FDA review process closely, as approval could significantly impact Alnylam's revenue projections and market position in the ATTR amyloidosis treatment landscape. The company's focus on launch preparation and potential market leadership in ATTR-CM, as highlighted in their investor day, further underscores the strategic importance of this submission.
− sNDA is Based on Full Findings from the Positive HELIOS-B Phase 3 Study –
− Priority Review Voucher Utilized to Accelerate Review Period –
− Alnylam to Host and Webcast TTR Investor Day Event Today in
“We are proud that with this first regulatory submission, we are a significant step closer to bringing vutrisiran to patients with ATTR amyloidosis with cardiomyopathy, which is a steadily progressive, debilitating, and ultimately fatal disease. HELIOS-B demonstrated rapid knockdown of TTR with vutrisiran and an improvement in death and cardiovascular events, as well as delays in disease progression, with vutrisiran as compared to placebo, with consistent effects across all pre-specified subgroups,” said Pushkal Garg, M.D., Chief Medical Officer, Alnylam. “We believe that, pending regulatory approval, vutrisiran has the potential to become a first-line therapy for ATTR amyloidosis with cardiomyopathy. We look forward to working with the FDA over the coming months on this application to bring this medicine to patients as rapidly as possible. Additional filings in other geographies are underway.”
The application to the FDA was based on positive results from HELIOS-B, a Phase 3, randomized, double-blind, placebo-controlled multicenter global study in patients with ATTR-CM with substantial background use of other effective therapies. The study demonstrated favorable effects of vutrisiran on outcomes of death and cardiovascular events, functional capacity and quality of life in patients with ATTR-CM. The safety profile of vutrisiran in HELIOS-B was consistent with the established profile of the drug. 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.
Today, the Company will host its TTR Investor Day starting at 8:30 am ET in
HELIOS-B Study Design
HELIOS-B (NCT: NCT04153149) was a Phase 3, randomized, double-blind, placebo-controlled multicenter global study designed and powered to evaluate the efficacy and safety of vutrisiran on the reduction of all-cause mortality and recurrent cardiovascular events as a primary composite endpoint in patients with ATTR amyloidosis with cardiomyopathy. The study randomized 655 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy. Patients were randomized 1:1 to receive vutrisiran 25mg or placebo subcutaneously once every three months during a double-blind treatment period of up to 36 months. After the double-blind period, all eligible patients remaining on the study to were able receive vutrisiran in an open-label extension period of HELIOS-B.
AMVUTTRA® (vutrisiran)
Indication
AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
Important Safety Information
Reduced Serum Vitamin A Levels and Recommended Supplementation
AMVUTTRA® (vutrisiran) 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
The most common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (
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 mutant and wild-type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, 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. 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. For more information about AMVUTTRA, including the full
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; the potential for vutrisiran to obtain regulatory approval for the treatment of ATTR amyloidosis with cardiomyopathy; the safety and efficacy of vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy, the potential of vutrisiran to including its potential to become a first-line therapy and a market-leading therapy for patients with ATTR amyloidosis with cardiomyopathy,; and Alnylam’s view with respect to the timing of regulatory review potential for a reduced review timeline by the FDA and any resulting approval(s) of vutrisiran for the treatment of ATTR amyloidosis in the
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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 is the purpose of Alnylam's sNDA submission for vutrisiran (ALNY)?
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What is the current approved indication for AMVUTTRA (vutrisiran) by Alnylam (ALNY)?
