Alnylam Announces Interim Phase 1 Data of Nucresiran (ALN-TTRsc04) Showing Rapid Knockdown of TTR that is Sustained at Six Months Following a Single Dose
Alnylam Pharmaceuticals presented new Phase 1 study results for nucresiran, a next-generation RNAi therapeutic for ATTR amyloidosis treatment. A single dose of ≥300mg achieved rapid TTR knockdown of >90% by Day 15, sustained through Day 180. Peak reductions of >96% were reached by Day 29. At 300mg, TTR reduction remained >70% at Day 360. The drug showed encouraging safety profile with low inter-patient variability. The 600mg dose achieved 95.0% TTR reduction at Day 15 and 96.0% at Day 180, while the 900mg dose showed 91.7% reduction at Day 15 and 94.2% at Day 180. The data supports potential biannual or annual dosing regimens.
Alnylam Pharmaceuticals ha presentato nuovi risultati dello studio di Fase 1 per nucresiran, una terapia RNAi di nuova generazione per il trattamento dell'amiloidosi ATTR. Una singola dose di ≥300mg ha raggiunto una riduzione rapida del TTR di oltre il 90% entro il 15° giorno, mantenendosi fino al 180° giorno. Le riduzioni massime superiori al 96% sono state raggiunte entro il 29° giorno. A 300mg, la riduzione del TTR è rimasta superiore al 70% al 360° giorno. Il farmaco ha mostrato un profilo di sicurezza incoraggiante con bassa variabilità inter-paziente. La dose di 600mg ha raggiunto una riduzione del TTR del 95,0% al 15° giorno e del 96,0% al 180° giorno, mentre la dose di 900mg ha mostrato una riduzione del 91,7% al 15° giorno e del 94,2% al 180° giorno. I dati supportano potenziali regimi di dosaggio biannuali o annuali.
Alnylam Pharmaceuticals presentó nuevos resultados del estudio de Fase 1 para nucresiran, una terapia RNAi de nueva generación para el tratamiento de la amiloidosis ATTR. Una sola dosis de ≥300mg logró una reducción rápida del TTR de más del 90% para el día 15, sustentándose hasta el día 180. Se alcanzaron reducciones máximas de más del 96% para el día 29. A 300mg, la reducción del TTR se mantuvo por encima del 70% en el día 360. El medicamento mostró un perfil de seguridad alentador con baja variabilidad entre pacientes. La dosis de 600mg logró una reducción del TTR del 95,0% en el día 15 y del 96,0% en el día 180, mientras que la dosis de 900mg mostró una reducción del 91,7% en el día 15 y del 94,2% en el día 180. Los datos respaldan posibles regímenes de dosificación semestrales o anuales.
Alnylam Pharmaceuticals는 ATTR 아밀로이드증 치료를 위한 차세대 RNAi 치료제 nucresiran에 대한 새로운 1상 연구 결과를 발표했습니다. ≥300mg의 단일 투여량이 15일째 TTR을 90% 이상 신속하게 억제하였고, 180일째까지 지속되었습니다. 29일째에는 96% 이상의 최대 감소에 달했습니다. 300mg에서 TTR 감소는 360일째 70% 이상이 유지되었습니다. 이 약물은 낮은 환자 간 변동성을 보여주는 고무적인 안전성 프로필을 보였습니다. 600mg 투여량은 15일째에 TTR을 95.0% 감소시켰고, 180일째에는 96.0% 감소하였습니다. 900mg 투여량은 15일째에 91.7% 감소, 180일째에 94.2% 감소를 보였습니다. 이 데이터는 잠재적인 반년 또는 연간 투여 요법을 지지합니다.
Alnylam Pharmaceuticals a présenté de nouveaux résultats d'étude de phase 1 pour nucresiran, une thérapie RNAi de nouvelle génération pour le traitement de l'amiloïdose ATTR. Une seule dose de ≥300mg a permis d'atteindre une réduction rapide du TTR de plus de 90 % au jour 15, maintenue jusqu'au jour 180. Des réductions maximales de plus de 96 % ont été atteintes au jour 29. À 300mg, la réduction du TTR est restée supérieure à 70 % au jour 360. Le médicament a montré un profil de sécurité encourageant, avec une faible variabilité inter-patients. La dose de 600mg a atteint une réduction du TTR de 95,0 % au jour 15 et de 96,0 % au jour 180, tandis que la dose de 900mg a montré une réduction de 91,7 % au jour 15 et de 94,2 % au jour 180. Les données soutiennent des régimes posologiques semestriels ou annuels potentiels.
Alnylam Pharmaceuticals hat neue Ergebnisse der Phase-1-Studie für nucresiran, eine neuartige RNAi-Therapie zur Behandlung der ATTR-Amyloidose, präsentiert. Eine Einzel Dosis von ≥300mg erzielte eine rasche TTR-Reduktion von über 90% bis zum 15. Tag, die bis zum 180. Tag anhielt. Höchstrückgänge von über 96% wurden bis zum 29. Tag erreicht. Bei 300mg blieb die TTR-Reduktion am 360. Tag über 70%. Das Medikament zeigte ein ermutigendes Sicherheitsprofil mit niedriger interindividueller Variabilität. Die Dosis von 600mg erreichte eine TTR-Reduktion von 95,0% am 15. Tag und 96,0% am 180. Tag, während die Dosis von 900mg am 15. Tag eine Reduktion von 91,7% und am 180. Tag von 94,2% zeigte. Die Daten unterstützen potenzielle halbjährliche oder jährliche Dosierungsschemata.
- Single dose ≥300mg achieved >90% TTR reduction by Day 15
- Sustained efficacy with >70% TTR reduction at Day 360 (300mg dose)
- Low inter-patient variability in TTR reduction across all doses
- Well-tolerated safety profile with no significant adverse events
- Potential for biannual or annual dosing frequency
- 360-day data not yet available for 600mg and 900mg doses
Insights
The Phase 1 data for nucresiran demonstrates exceptional clinical potential in ATTR amyloidosis treatment. The sustained TTR reduction of >90% for six months from a single dose is remarkable, surpassing current treatment paradigms. The low inter-patient variability (96.0-98.6% reduction across dose cohorts) suggests highly predictable treatment outcomes.
The durability profile supporting biannual or annual dosing could revolutionize ATTR amyloidosis treatment. Current standards require more frequent administration. The clean safety profile with no injection site reactions or liver signals is particularly noteworthy for this drug class. The 71.12% TTR reduction at one year from a single 300mg dose indicates breakthrough potential for long-term disease management.
These results position nucresiran as a potential market leader in the $11 billion ATTR amyloidosis market. The extended dosing interval could provide Alnylam significant competitive advantages over existing treatments like Onpattro (every 3 weeks) and Amvuttra (quarterly). The impressive efficacy and convenience profile could drive strong market adoption and premium pricing.
With Phase 3 plans expected in Q1 2025, nucresiran represents a major catalyst for Alnylam's long-term growth. The IKARIA platform validation through these results also enhances the company's broader pipeline value. The potential for annual dosing could significantly reduce healthcare costs while improving patient compliance.
− Single Dose of Nucresiran 300mg or Higher Led to Rapid Knockdown of Mean TTR Levels of Greater than
− At These Doses, Peak Reduction of Mean TTR Levels of Greater than
− Data Support Potential for Biannual or Annual Subcutaneous Dosing, Representing a New Paradigm in the Treatment of ATTR Amyloidosis −
− Encouraging Safety and Tolerability Observed −
− Alnylam Continues to Expect to Share Phase 3 Development Plans in Q1 2025 –
These new results demonstrated that a single dose of nucresiran at 300 mg or higher led to rapid knockdown of serum TTR with low inter-patient variability, with mean reductions of greater than
“We are very excited by these new Phase 1 data with nucresiran, our next-generation TTR-targeting RNAi therapeutic, which demonstrated that a single dose of ≥300 mg achieved rapid knockdown of TTR greater than
The ongoing Phase 1 dose-finding study evaluated the safety, as well as pharmacodynamics and pharmacokinetics, of single doses of nucresiran in healthy subjects. As previously presented at Alnylam’s R&D Day in December 2023, a single dose of nucresiran led to rapid knockdown of serum TTR that was highly durable.
In subjects receiving a single 300 mg dose of nucresiran, mean serum TTR reduction of
There has been low inter-patient variability in the TTR reduction observed; at Day 29, TTR reduction ranged from 96.0 –
In the study, nucresiran has been well tolerated at all tested doses. The majority of adverse events across doses have been mild and none have been considered to be related to treatment. There have been no injection site reactions and no safety signals identified, including no liver-related signals.
Phase 1 Study Design
The Phase 1 trial is a randomized, double-blind, placebo-controlled, single ascending dose study designed to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of nucresiran in healthy adult subjects. The study enrolled 48 healthy adult subjects randomized 3:1 to receive a single ascending dose of 5, 25, 100, 300, 600, or 900 mg of nucresiran or placebo. The primary endpoint of the study is safety and secondary endpoints include the change from baseline in serum TTR over time, as well as characterization of plasma and urine pharmacokinetics (PK) of nucresiran.
About Nucresiran
Nucresiran is an investigational RNAi therapeutic in development to deliver rapid knockdown of mutant and wild-type transthyretin (TTR) and address the underlying cause of transthyretin (ATTR) amyloidosis. As part of Alnylam’s proprietary IKARIA™ platform, nucresiran has the potential to achieve deeper and more durable rapid knockdown of TTR, allowing for less frequent dosing. The safety and efficacy of nucresiran have not been established or evaluated by the FDA, EMA or any other health authority.
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.
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 (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, the potential for nucresiran to achieve durability supportive of biannual or annual dosing and to represent a new paradigm in the treatment of ATTR amyloidosis; the potential to reduce interpatient variability in TTR lowering with nucresiran; and the timing of Alnylam’s release of Phase 3 development plans for nucresiran 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; actions or advice of regulatory agencies and Alnylam’s ability to obtain regulatory approval for its product candidates, 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.
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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
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