revusiran (ALN-TTRsc) / Alnylam, Sanofi - LARVOL DELTA

Disease-Modifying Therapies for Transthyretin Amyloid Cardiomyopathy: A Systematic Review and Meta-Analysis. (PubMed, Arq Bras Cardiol) - "TTR stabilizers significantly reduced all-cause mortality and hospitalizations in patients with ATTR-CM compared with placebo. These benefits were not observed with TTR silencers, potentially due to shorter follow-up durations in the studies evaluated. Both therapies improved functional status and serum levels of NT-proBNP."

Biomarker • Clinical • Journal • Retrospective data • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Safety and effectiveness of interference RNA (RNAi) based therapeutics in cardiac failure: A systematic review. (PubMed, Heart Lung) - "RNAi therapeutics are novel treatment option for improving cardiac function because their high target specificity, ability to target genes that conventional drugs struggle to reach and potential for long-lasting effects. Further research on optimizing delivery methods, improving target specificity, evaluating long-term safety profiles and cost-effectiveness to fully realize their potential."

Journal • Review • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Hepatology • Hypertrophic Cardiomyopathy • Infectious Disease • Myocardial Infarction • Nephrology • Pain • Peripheral Neuropathic Pain • Vaginitis • DUSP5 • MEG3

Pharmacological Management of Transthyretin Amyloid Cardiomyopathy: A scoping review. (PubMed, Eur Heart J Cardiovasc Pharmacother) - "Multiple pharmacological options are potential disease-modifying therapies for ATTR-CM. However, many gaps exist in the understanding of these various drug therapies, warranting further research. The future directions for management of ATTR-CM are promising in regard to improving prognostic implications."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Targeted Therapeutics for Transthyretin Amyloid Cardiomyopathy. (PubMed, Am J Ther) - "Evidence from the pooled analysis revealed targeted therapeutics improve survival and are well-tolerated. These findings suggest a potential role for targeted therapeutics in the treatment of patients with ATTR-CM."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Phase 3 Multicenter Study of Revusiran in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Cardiomyopathy (ENDEAVOUR). (PubMed, Cardiovasc Drugs Ther) - P3 | "Causes for the observed mortality imbalance associated with revusiran were thoroughly investigated and no clear causative mechanism could be identified. Although the results suggest similar progression of cardiac parameters in both treatment arms, a role for revusiran cannot be excluded."

Clinical • Journal • P3 data • Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a 'treatabolome'. (PubMed, J Neuromuscul Dis) - "The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies."

Journal • Review • Genetic Disorders • Pain

Single Dose Pharmacokinetics and Pharmacodynamics of Transthyretin Targeting GalNAc-siRNA Conjugate, Vutrisiran, in Healthy Subjects. (PubMed, Clin Pharmacol Ther) - "Vutrisiran (ALN-TTRsc02) is a liver-directed, investigational, small interfering ribonucleic acid drug for the treatment of transthyretin (TTR)-mediated amyloidosis. Vutrisiran had an acceptable safety profile; the most common treatment-related adverse event was mild, transient injection site reactions in four (6.7%) vutrisiran-treated subjects. The favorable pharmacokinetic, pharmacodynamic, and safety results observed here support vutrisiran's continued clinical development."

Clinical • Journal • PK/PD data • Amyloidosis

"$ALNY This is an expensive treatment to administer and do trials. "Alnylam will fund all development and commercialization costs for patisiran and ALN-TTRsc02 going forward." $SNY $IONS" (@IonisDisrupts)

Pricing • Biosimilar

HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis) (clinicaltrials.gov) - P3; N=164; Active, not recruiting; Sponsor: Alnylam Pharmaceuticals; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Nonclinical Safety Profile of Revusiran, a 1st-Generation GalNAc-siRNA Conjugate for Treatment of Hereditary Transthyretin-Mediated Amyloidosis. (PubMed, Nucleic Acid Ther) - "There was no evidence of genotoxicity in vitro or in vivo at limit doses or carcinogenicity in a 2-year study in rats at doses up to 100 mg/kg. Overall, these results demonstrate that revusiran had a favorable nonclinical safety profile."

Clinical • Journal • ASGR

HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (clinicaltrials.gov) - P3; N=600; Recruiting; Sponsor: Alnylam Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (clinicaltrials.gov) - P3; N=600; Not yet recruiting; Sponsor: Alnylam Pharmaceuticals

Clinical • New P3 trial

Safety evaluation of 2'-deoxy-2'-fluoro nucleotides in GalNAc-siRNA conjugates. (PubMed, Nucleic Acids Res) - "Because 2'-deoxy-2'-fluoro (2'-F) nucleotides are not known to occur naturally, their safety profile was assessed when used in revusiran and ALN-TTRSC02, two short interfering RNAs (siRNAs), of the same sequence but different chemical modification pattern and metabolic stability, conjugated to an N-acetylgalactosamine (GalNAc) ligand for targeted delivery to hepatocytes. No apparent functional impact on mitochondria and no significant accumulation of 2'-F-monomers were observed after weekly administration of two GalNAc-siRNA conjugates in rats for ∼2 years. Taken together, the results support the conclusion that 2'-F nucleotides can be safely applied for the design of metabolically stabilized therapeutic GalNAc-siRNAs with favorable potency and prolonged duration of activity allowing for low dose and infrequent dosing."

Clinical • Journal

Targeted Therapeutics for Transthyretin amyloid cardiomyopathy: Time to Move Forward (HFSA 2019) - "Targeted therapeutics (TT) for ATTR-CA include TTR stabilizers (tafamidis, dilfunisal) and oligonucleotide drugs (Revusiran, Patisiran and Inotersen).TTR stabilizers prevent dissociation of amyloid tetramers and thereby limit the deposition of amyloid fibrils. sIn patients with ATTR-CA, TT reduced all-cause mortality and were well-tolerated as compared to placebo."

"Equally well except for revusiran." (@biotech_batman)

Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis. (PubMed, J Clin Neuromuscul Dis) - "A sural nerve biopsy demonstrated demyelination with substantial axonal loss in the absence of histologically detectable endoneurial amyloid deposition. This case expands the clinicopathologic spectrum of transthyretin amyloidosis and may represent complex disease and treatment effects."

Clinical • Journal

HELIOS-A: A Clinical Study to Assess the Effectiveness and Safety of an Investigational Drug, ALN-TTRSC02, in Patients with Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis) (clinicaltrialsregister.eu) - P3; N=160; Ongoing; Sponsor: Alnylam Pharmaceuticals, Inc.

Clinical • New P3 trial

HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis) (clinicaltrials.gov) - P3; N=160; Recruiting; Sponsor: Alnylam Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open