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Alnylam Pharmaceuticals (Nasdaq: ALNY) presented new data from the HELIOS-B Phase 3 study of vutrisiran for ATTR amyloidosis with cardiomyopathy (ATTR-CM) at the HFSA Annual Scientific Meeting 2024. The data showed that vutrisiran significantly improved echocardiographic assessments of cardiac structure, systolic function, and diastolic function compared to placebo over 30 months. Vutrisiran also demonstrated relative stability of cardiac biomarkers NT-proBNP and Troponin-I.
Key findings include:
- Improvements in cardiac wall structure, diastolic function, and systolic function
- 32% relative reduction in NT-proBNP and troponin I in the overall population
- Larger treatment effects observed in the monotherapy population
Alnylam plans to complete multiple global regulatory submissions for vutrisiran in ATTR-CM by the end of the year.
Alnylam Pharmaceuticals (Nasdaq: ALNY) ha presentato nuovi dati dallo studio HELIOS-B di fase 3 su vutrisiran per l’amiloidosi da transtiretina con cardiomiopatia (ATTR-CM) durante l’incontro scientifico annuale HFSA 2024. I dati hanno mostrato che vutrisiran ha significativamente migliorato le valutazioni ecocardiografiche della struttura cardiaca, della funzione sistolica e della funzione diastolica rispetto al placebo nel corso di 30 mesi. Inoltre, vutrisiran ha dimostrato una stabilità relativa dei biomarcatori cardiaci NT-proBNP e Troponin-I.
I risultati chiave includono:
- Modifiche nella struttura della parete cardiaca, nella funzione diastolica e nella funzione sistolica
- Riduzione relativa del 32% di NT-proBNP e troponina I nell’intera popolazione
- Maggiore efficacia del trattamento osservata nella popolazione in monoterapia
Alnylam prevede di completare diverse sottomissioni regolatorie globali per vutrisiran nell’ATTR-CM entro la fine dell’anno.
Alnylam Pharmaceuticals (Nasdaq: ALNY) presentó nuevos datos del estudio HELIOS-B de fase 3 sobre vutrisiran para la amiloidosis ATTR con cardiomiopatía (ATTR-CM) en la reunión científica anual de HFSA 2024. Los datos mostraron que vutrisiran mejoró significativamente las evaluaciones ecocardiográficas de la estructura cardíaca, la función sistólica y la función diastólica en comparación con el placebo durante 30 meses. Vutrisiran también demostró estabilidad relativa de los biomarcadores cardíacos NT-proBNP y Troponina-I.
Las conclusiones clave incluyen:
- Mejoras en la estructura de la pared cardíaca, función diastólica y función sistólica
- Reducción relativa del 32% en NT-proBNP y troponina I en la población general
- Efectos del tratamiento más pronunciados observados en la población con monoterapia
Alnylam planea completar múltiples presentaciones regulatorias globales para vutrisiran en ATTR-CM para fin de año.
Alnylam Pharmaceuticals (Nasdaq: ALNY)는 HFSA 연례 과학 회의 2024에서 ATTR cardiomyopathy (ATTR-CM) 환자를 위한 vutrisiran의 HELIOS-B 3상 연구의 새로운 데이터를 발표했습니다. 데이터에 따르면 vutrisiran은 위약과 비교하여 30개월 동안 심장 구조, 수축 기능 및 이완 기능의 초음파 평가를 상당히 개선했습니다. vutrisiran은 또한 심장 바이오마커인 NT-proBNP 및 Troponin-I의 상대적 안정성을 나타냈습니다.
주요 발견 사항은 다음과 같습니다:
- 심장 벽 구조, 이완 기능 및 수축 기능의 개선
- 전체 인구에서 NT-proBNP 및 Troponin I의 32% 상대적 감소
- 단독 요법 집단에서 더 큰 치료 효과가 관찰됨
Alnylam은 ATTR-CM을 위한 vutrisiran의 여러 글로벌 규제 제출을 연말까지 완료할 계획입니다.
Alnylam Pharmaceuticals (Nasdaq: ALNY) a présenté de nouvelles données de l’étude HELIOS-B de phase 3 sur le vutrisiran pour l’amyloïdose ATTR avec cardiomyopathie (ATTR-CM) lors de la réunion scientifique annuelle de la HFSA 2024. Les données ont montré que le vutrisiran a considérablement amélioré les évaluations échocardiographiques de la structure cardiaque, de la fonction systolique et de la fonction diastolique par rapport au placebo sur 30 mois. Le vutrisiran a également démontré une stabilité relative des biomarqueurs cardiaques NT-proBNP et Troponine-I.
Les résultats clés incluent :
- Améliorations de la structure de la paroi cardiaque, de la fonction diastolique et de la fonction systolique
- Réduction relative de 32 % des NT-proBNP et de la troponine I dans la population totale
- Effets du traitement plus importants observés dans la population en monothérapie
Alnylam prévoit de finaliser plusieurs soumissions réglementaires mondiales pour le vutrisiran dans l’ATTR-CM d’ici la fin de l’année.
Alnylam Pharmaceuticals (Nasdaq: ALNY) hat neue Daten aus der HELIOS-B Phase 3-Studie zu vutrisiran bei ATTR-Amyloidose mit Kardiomyopathie (ATTR-CM) auf der HFSA-Jahreswissenschaftstagung 2024 vorgestellt. Die Daten zeigten, dass vutrisiran die echokardiographischen Bewertungen der Herzstruktur, der systolischen Funktion und der diastolischen Funktion im Vergleich zu Placebo über 30 Monate signifikant verbesserte. Vutrisiran zeigte auch eine relative Stabilität der Herzbiomarker NT-proBNP und Troponin-I.
Wichtige Ergebnisse umfassen:
- Verbesserungen in der Herzwandstruktur, diastolischen Funktion und systolischen Funktion
- 32% relative Reduktion von NT-proBNP und Troponin I in der Gesamtbevölkerung
- Größere Behandlungseffekte in der Monotherapiepopulation beobachtet
Alnylam plant, bis zum Ende des Jahres mehrere globale Zulassungsanträge für vutrisiran bei ATTR-CM abzuschließen.
Positive
- Vutrisiran significantly improved echocardiographic assessments of cardiac structure, systolic function, and diastolic function compared to placebo over 30 months
- 32% relative reduction in NT-proBNP and troponin I biomarkers in the overall population at Month 30
- 43% relative reduction in NT-proBNP and 45% reduction in troponin I in the monotherapy population at Month 30
- Significant improvements in diastolic and systolic function observed as early as 12 and 18 months, respectively
- Consistent results across all pre-specified subgroups
- Alnylam plans to complete multiple global regulatory submissions for vutrisiran in ATTR-CM by year-end
Insights
The HELIOS-B study results for vutrisiran in ATTR-CM are highly promising. The data shows significant improvements across multiple cardiac parameters:
- Reduced left ventricular wall thickness and mass index, indicating improved cardiac structure
- Enhanced diastolic and systolic function measures like E/A ratio, E/e’ ratio and global longitudinal strain
- Decreased NT-proBNP and troponin I levels, key biomarkers of cardiac stress and injury
These improvements were observed as early as 6-18 months and maintained through 30 months, suggesting a potential disease-modifying effect. The benefits were more pronounced in the monotherapy group, highlighting vutrisiran’s standalone efficacy. With a 32% relative reduction in NT-proBNP and troponin I in the overall population, vutrisiran demonstrates meaningful impact on cardiac health in ATTR-CM patients.
These results position vutrisiran as a strong candidate for first-line therapy in ATTR-CM, potentially offering a new treatment paradigm. The planned regulatory submissions by year-end could lead to a significant market opportunity for Alnylam in the growing ATTR-CM space.
− Echocardiographic and Cardiac Biomarker Data From the HELIOS-B Study Presented Today Support the Potential of Vutrisiran in ATTR-CM –
− Vutrisiran Significantly Improved Echocardiographic Assessments of Cardiac Structure, Systolic Function and Diastolic Function Relative to Placebo Over 30 Months –
− Vutrisiran Demonstrated Relative Stability of Cardiac Biomarkers NT-proBNP and Troponin-I Relative to Placebo Over 30 Months –
CAMBRIDGE, Mass.–(BUSINESS WIRE)– Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that two new data sets from the HELIOS-B Phase 3 study of vutrisiran, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM), were presented in the Late Breaking Clinical Research Session 1 at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2024, which was held virtually. An open access recording of Alnylam presentations will be available on the HFSA website following the session.
Progression in ATTR-CM is associated with cardiac wall thickening, deterioration in systolic and diastolic function and increases in biomarkers of cardiac stress and injury, NT-pro-BNP and Troponin I.
“Consistent with demonstrated improvements in outcomes and health status, these new data show that vutrisiran attenuated measures of disease progression across multiple domains of cardiac structure and function, NT-proBNP and troponin I, in a contemporary ATTR-CM patient population,” said Pushkal Garg, M.D., Chief Medical Officer, Alnylam. “These data demonstrate that rapid knockdown of TTR leads to an early impact on cardiac biomarkers and echocardiographic parameters, indicative of a potential disease-modifying effect, and underscores the benefit of treating patients with an RNAi therapeutic earlier in the course of disease. We remain confident that, with approval, vutrisiran has the potential to become a first-line therapy for ATTR amyloidosis with cardiomyopathy and are on track to complete multiple global regulatory submissions before the end of the year.”
Analysis results
New echocardiographic data demonstrated that treatment with vutrisiran slowed disease progression in a contemporary population of patients with ATTR-CM across multiple domains of cardiac structure and diastolic and systolic function at Month 30 as compared to placebo. The magnitude of the treatment effects with vutrisiran compared to placebo were similar or greater in the monotherapy population. Significant improvements in both diastolic and systolic function were observed as early as 12 months and 18 months, respectively, in the overall population. The Month 30 results in the overall population are detailed in the table below.*
|
|
Overall population |
|
Cardiac Wall Structure |
|
|
Mean Left Ventricular Wall Thickness |
-0.04 cm |
|
Left Ventricular Mass Index |
-10.6 g/m2 |
|
Left Ventricular Diastolic Function |
|
|
E/A Ratio |
-0.29 |
|
E/e’ Ratio |
-1.82 |
|
TDI Lateral e’ |
0.55 cm/s |
|
Left Ventricular Systolic Function |
|
|
Left Ventricular Ejection Fraction |
2.03% |
|
Absolute Global Longitudinal Strain |
1.23% |
|
Left Ventricular Stroke Volume |
4.05 mL |
*All p-values included within the table are nominal p-values.
In addition, analyses of cardiac biomarkers NT-proBNP and troponin I were also presented. At Month 30, the relative reduction in the fold change in NT-proBNP in patients treated with vutrisiran compared to placebo was 32% in the overall population and 43% in the monotherapy population (adjusted geometric mean fold change ratio [vutrisiran/placebo]: 0.68; nominal p-value 3.440E-12 and 0.57; nominal p-value 4.339E-12, respectively). At Month 30, relative reduction in the fold change of troponin I was 32% in the overall population and 45% in the monotherapy population (adjusted geometric mean fold change ratio [vutrisiran/placebo]: 0.68; nominal p-value 1.566E-14 and 0.55; nominal p-value 9.684E-17, respectively).
In the subgroup of patients receiving tafamidis at baseline, a relative reduction in the fold change of 18% was observed in NT-proBNP and 10% in troponin I (adjusted geometric mean fold change ratio [vutrisiran/placebo]: 0.82; nominal p-value 0.0045 and 0.90; nominal p-value 0.0849, respectively) at Month 30. For both NTproBNP and troponin I, patients treated with vutrisiran demonstrated nominally significant reductions relative to placebo at 6 months. These results were consistent across all pre-specified subgroups, with a larger treatment effect observed in the monotherapy population.
Detailed results from the HELIOS-B study were presented at the European Society of Cardiology annual congress on August 30, 2024, and simultaneously published in The New England Journal of Medicine.
Alnylam plans to include a discussion of these data at its upcoming TTR Investor Day on Wednesday, October 9, 2024, at 8:30 am ET in New York City. The event will be webcast on the Investors section of the Company’s website, www.alnylam.com. A replay will be available on the Alnylam website within 48 hours after the event.
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.
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 for polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) were arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%).
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 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.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 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 amyloidosis with cardiomyopathy, including its potential to become a first-line therapy for patients with ATTR amyloidosis with cardiomyopathy, and the timing of Alnylam’s global 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” 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.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240929319308/en/
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 were the key findings of the HELIOS-B study for vutrisiran in ATTR-CM presented at HFSA 2024?
The HELIOS-B study showed that vutrisiran significantly improved echocardiographic assessments of cardiac structure, systolic function, and diastolic function compared to placebo over 30 months. It also demonstrated relative stability of cardiac biomarkers NT-proBNP and Troponin-I, with a 32% relative reduction in both biomarkers in the overall population at Month 30.
When does Alnylam (ALNY) plan to submit regulatory applications for vutrisiran in ATTR-CM?
Alnylam plans to complete multiple global regulatory submissions for vutrisiran in ATTR-CM by the end of the year, as stated in the press release.
What were the echocardiographic improvements seen with vutrisiran in the HELIOS-B study?
Vutrisiran showed improvements in cardiac wall structure, left ventricular diastolic function, and left ventricular systolic function compared to placebo at Month 30. Specific measures included improvements in left ventricular wall thickness, mass index, E/A ratio, E/e’ ratio, ejection fraction, and global longitudinal strain.
How did vutrisiran affect cardiac biomarkers in ATTR-CM patients in the HELIOS-B trial?
Vutrisiran demonstrated a 32% relative reduction in both NT-proBNP and troponin I biomarkers in the overall population at Month 30. In the monotherapy population, there was a 43% relative reduction in NT-proBNP and a 45% reduction in troponin I at Month 30.
