nucresiran (ALN-TTRsc04) / Alnylam - LARVOL DELTA

TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (clinicaltrials.gov) - P3 | N=125 | Not yet recruiting | Sponsor: Alnylam Pharmaceuticals

New P3 trial • Amyloidosis • Cardiac Amyloidosis • Pain

ALN-TTRSC04-001: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALN-TTRSC04 in Healthy Subjects (clinicaltrials.gov) - P1 | N=96 | Completed | Sponsor: Alnylam Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Amyloidosis

Design And Rationale Of A Phase 3 Study To Evaluate The Efficacy And Safety Of Nucresiran (aln-ttrsc04) In Patients With Transthyretin Amyloidosis With Cardiomyopathy (HFSA 2025) - P1 | "Most recently, vutrisiran was shown to improve outcomes for patients with ATTR-CM across multiple domains in the HELIOS-B study, including reducing cardiovascular events and all-cause mortality, and improving functional capacity and quality of life. The Phase 3 study will investigate the efficacy, safety, and PK/PD of nucresiran in patients with ATTR-CM. Nucresiran has the potential to provide greater and more sustained TTR knockdown with lower inter-patient variability and less frequent dosing than current TTR-lowering therapies. This abstract will be presented at HFA 2025, May 17-20, 2025, Belgrade, Serbia."

Clinical • P3 data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Key Upcoming Events (Businesswire) - "Alnylam announces today that it will present results from the KARDIA-3 Phase 2 trial of zilebesiran in patients with hypertension during a Hot Line Session at the European Society of Cardiology (ESC) Congress in Madrid, Spain on August 30, 2025...In addition, in the second half of 2025, Alnylam expects to: Initiate a Phase 3 cardiovascular outcomes trial of zilebesiran, in collaboration with its partner Roche; Initiate the TRITON-PN Phase 3 trial of nucresiran in hATTR-PN; Initiate a Phase 2 trial of mivelsiran in Alzheimer’s disease....In addition, Alnylam's partner, Regeneron Pharmaceuticals, plans to share results from the Phase 3 trial of cemdisiran tested as a monotherapy and in combination with pozelimab in patients with myasthenia gravis in the second half of 2025."

Clinical data • New P2 trial • New P3 trial • Alzheimer's Disease • Amyloidosis • Cardiovascular • Hypertension • Myasthenia Gravis

ALN-TTRSC04-001: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALN-TTRSC04 in Healthy Subjects (clinicaltrials.gov) - P1 | N=96 | Active, not recruiting | Sponsor: Alnylam Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=180 ➔ 96

Enrollment change • Enrollment closed • Amyloidosis

Second Quarter 2025 and Recent Significant Business Highlights (Businesswire) - "Achieved global net product revenues for AMVUTTRA and ONPATTRO for the second quarter of $492 million and $53 million, respectively, representing $544 million in total TTR net product revenues and 77% total TTR growth compared to Q2 2024; Achieved approximately 1,400 ATTR-CM patients on AMVUTTRA as of June 30, 2025....Alnylam announces today that nucresiran has received Fast Track Designation from the FDA's Division of Cardiology and Nephrology for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin mediated amyloidosis in adults to reduce mortality, cardiovascular hospitalizations, and urgent heart failure visits."

Fast track • Sales • Amyloidosis • Cardiomyopathy

TRITON-CM: A Study to Evaluate Nucresiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (clinicaltrials.gov) - P3 | N=1250 | Recruiting | Sponsor: Alnylam Pharmaceuticals

New P3 trial • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Design and rationale of a phase 3 study to evaluate the efficacy and safety of nucresiran (ALN-TTRsc04) in patients with transthyretin amyloidosis with cardiomyopathy (HEART FAILURE 2025) - "Most recently, vutrisiran was shown to improve outcomes for patients with ATTR-CM across multiple domains in the HELIOS-B study, including reducing cardiovascular events and all-cause mortality, and improving functional capacity and quality of life (3). The phase 3 study will investigate the efficacy, safety and PK/PD of nucresiran in patients with ATTR-CM. Nucresiran has the potential to provide greater and more sustained TTR knockdown with lower inter-patient variability and less frequent dosing than current TTR-lowering therapies."

Clinical • P3 data • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Alnylam to Share Progress Across its Transthyretin Amyloidosis Franchise Including Additional Analyses of the HELIOS-B Phase 3 Study Results at Heart Failure 2025 Congress (Businesswire) - "Alnylam Pharmaceuticals, Inc...announced that the Company will present the latest data from its flagship transthyretin amyloidosis (TTR) franchise at the upcoming Heart Failure 2025 Congress, a scientific congress of the European Society of Cardiology, taking place May 17-20 in Belgrade, Serbia...The latest analyses of the HELIOS-B Phase 3 study of vutrisiran in patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM), including further outcomes data on cardiovascular hospitalizations and urgent heart failure visits up to 42-months, will be presented as a late-breaking abstract....Additional updates to be presented include the design and rationale of the TRITON-CM Phase 3 study of nucresiran (ALN-TTRsc04), an investigational next-generation TTR silencer, in patients with ATTR-CM, as well as an additional analysis from the HELIOS-B study of vutrisiran in patients with ATTR-CM who experienced disease progression while being treated with tafamidis."

Clinical data • Clinical protocol • Amyloidosis • Cardiomyopathy

Key Upcoming Events (Businesswire) - "Alnylam intends to initiate the TRITON-CM Phase 3 clinical trial of nucresiran in patients with ATTR-CM in the first half of 2025...Alnylam anticipates regulatory approval for AMVUTTRA for ATTR-CM in Japan in Q2 and in the European Union in Q3 of 2025...Alnylam also intends to release data from the KARDIA-3 Phase 2 clinical trial evaluating zilebesiran in combination with at least two antihypertensives in high cardiovascular risk patients with uncontrolled hypertension in the second half of 2025. These results will further inform the design of a Phase 3 cardiovascular outcomes trial for zilebesiran that Alnylam intends to initiate in the second half of 2025."

EMA approval • Japan approval • New P3 trial • P2 data • Amyloidosis • Cardiomyopathy • Cardiovascular • Hypertension

Alnylam Announces Preliminary Fourth Quarter and Full Year 2024 Global Net Product Revenues and Provides 2025 Combined Net Product Revenue Guidance and Pipeline Goals (Businesswire) - "Vutrisiran...Secure additional global approvals and reimbursement in Japan and the EU for the treatment of adults with ATTR amyloidosis with cardiomyopathy in the second half of 2025. Nucresiran (ALN-TTRsc04) – an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis. Alnylam expects to: Initiate a Phase 3 study in patients with ATTR amyloidosis with cardiomyopathy in the first half of 2025...Mivelsiran – an investigational RNAi therapeutic in development for the treatment of Alzheimer’s disease and cerebral amyloid angiopathy (CAA). Alnylam expects to: Report interim results from Part B of the Phase 1 study in Alzheimer’s disease in the second half of 2025. Initiate a Phase 2 study in Alzheimer’s disease in the second half of 2025...In 2025, Vir expects to initiate a Phase 3 chronic hepatitis delta registrational study and to report functional cure results from a Phase 2 chronic hepatitis B study."

Approval • New P2 trial • New P3 trial • P1 data • P2 data • Reimbursement • Alzheimer's Disease • Amyloidosis • CNS Disorders

A Phase 1, Single Ascending Dose Study to Evaluate ALN-TTRsc04, a Next-Generation RNA Interference Therapeutic, in Healthy Participants for Potential Treatment of Transthyretin Amyloidosis (AHA 2024) - P1 | "A single ALN-TTRsc04 dose led to a rapid and sustained knockdown in serum TTR; a reduction >90% from BL was sustained until Day 180 with the 300 mg dose. All ALN-TTRsc04 doses have been well tolerated to date; data through 12 months will be assessed."

Clinical • P1 data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Pain

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 (Businesswire) - P1 | N=180 | NCT05661916 | Sponsor: Alnylam Pharmaceuticals | "'Importantly, nucresiran has been well tolerated at all dose levels tested to date. We look forward to sharing Phase 3 development plans in the first quarter of 2025...In subjects receiving a single 300 mg dose of nucresiran, mean serum TTR reduction of 90.3% was observed at Day 15, 96.5% at Day 29, and 92.6% at Day 180. At Day 360, mean serum TTR Reduction was 71.12%. In subjects receiving a single 600 mg dose, mean serum TTR reduction of 95.0% was observed at Day 15, 97.8% at Day 29, and 96.0% at Day 180. In subjects receiving a single 900 mg dose, mean serum TTR reduction of 91.7% was observed at Day 15, 96.7% at Day 29, and 94.2% at Day 180. As of the data cutoff date, TTR knockdown levels at Day 360 were not available for either the 600 mg or 900 mg cohort."

P1 data • Amyloidosis • Metabolic Disorders

Alnylam Pharmaceuticals Reports Third Quarter 2024 Financial Results and Highlights Recent Period Activity (Businesswire) - "Continued growth momentum in total TTR, achieving global net product revenues for ONPATTRO and AMVUTTRA for the third quarter of $50 million and $259 million, respectively, which combined represent 34% TTR annual growth compared to Q3 2023...Alnylam will present additional findings from the ongoing Phase 1 study of ALN-TTRsc04 in patients with ATTR amyloidosis at the American Heart Association Scientific Sessions 2024. The Company plans to share its Phase 3 development plan for ALN-TTRsc04 in the first quarter of 2025. Alnylam intends to initiate a Phase 2 study of mivelsiran in patients with Alzheimer’s disease at or around year-end."

Commercial • New P2 trial • New P3 trial • P1 data • Alzheimer's Disease • Amyloidosis • CNS Disorders • Metabolic Disorders

Alnylam Pharmaceuticals Reports Second Quarter 2024 Financial Results and Highlights Recent Period Activity (Businesswire) - "In mid- and late 2024, Alnylam intends to: Submit a supplemental New Drug Application (sNDA) for vutrisiran to the FDA using a Priority Review Voucher. Initiate a Phase 3 study of ALN-TTRsc04 in patients with ATTR-CM at or around year-end. Report interim results from Part B of the Phase 1 study of mivelsiran (ALN-APP) in patients with Alzheimer’s disease. Initiate a Phase 2 study of mivelsiran in patients with Alzheimer’s disease at or around year-end. Initiate a Phase 1 study of ALN-BCAT, in development for the treatment of hepatocellular carcinoma."

FDA filing • New P1 trial • New P2 trial • New P3 trial • P1 data • Alzheimer's Disease • Amyloidosis • Cardiomyopathy • CNS Disorders • Hepatocellular Cancer • Liver Cancer • Metabolic Disorders • Oncology • Solid Tumor

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALN-TTRSC04 in Healthy Subjects (clinicaltrials.gov) - P1 | N=180 | Recruiting | Sponsor: Alnylam Pharmaceuticals

Trial completion date • Trial primary completion date • Amyloidosis

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALN-TTRSC04 in Healthy Subjects (clinicaltrials.gov) - P1 | N=180 | Recruiting | Sponsor: Alnylam Pharmaceuticals | Enrolling by invitation ➔ Recruiting | N=132 ➔ 180 | Trial completion date: Jun 2025 ➔ Sep 2025 | Trial primary completion date: Dec 2023 ➔ Sep 2025

Enrollment change • Enrollment status • Trial completion date • Trial primary completion date • Amyloidosis

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALN-TTRSC04 in Healthy Subjects (clinicaltrials.gov) - P1 | N=132 | Enrolling by invitation | Sponsor: Alnylam Pharmaceuticals | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Amyloidosis

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALN-TTRSC04 in Healthy Subjects (clinicaltrials.gov) - P1 | N=132 | Not yet recruiting | Sponsor: Alnylam Pharmaceuticals

New P1 trial • Amyloidosis

Alnylam Announces 2023 Product and Pipeline Goals and Provides Program Updates at R&D Day (Businesswire) - “Vutrisiran, a commercial-stage RNAi therapeutic for the treatment of polyneuropathy in patients with hATTR amyloidosis, and in development for the treatment of the cardiomyopathy of ATTR amyloidosis. Alnylam plans to: Report data from the evaluation of a biannual dosing regimen in early 2023. Submit a Supplemental New Drug Application (sNDA) for a biannual dosing regimen in early 2023. ALN-TTRsc04, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis. Alnylam plans to: Report topline Phase 1 results in late 2023….ALN-APP, an investigational RNAi therapeutic in development for the treatment of Alzheimer’s Disease and Cerebral Amyloid Angiopathy. Alnylam plans to: Report topline Phase 1 results in early 2023.”

Clinical data • P1 data • sNDA • Alzheimer's Disease • Amyloidosis • CNS Disorders • Tauopathies And Synucleinopathies

Alnylam Pharmaceuticals Reports Second Quarter 2022 Financial Results and Highlights Recent Period Activity (Businesswire) - “Upcoming Events: In addition, in mid- and late-2022, Alnylam intends to: Launch vutrisiran in the EU...for the treatment of hATTR amyloidosis patients with polyneuropathy; Report results on a biannual dose regimen for vutrisiran; File an Investigational New Drug (IND) application and initiate a Phase 1 study for ALN-TTRsc04 in healthy volunteers; Report preliminary results from the Phase 1 study of ALN-APP in patients with early-onset Alzheimer's disease.”

Clinical data • IND • Launch Europe • New P1 trial • P1 data • Alzheimer's Disease • Amyloidosis • CNS Disorders