Onpattro (patisiran) / Alnylam, Arbutus, Sanofi, Medison - LARVOL DELTA

Relative efficacy of tafamidis, acoramidis, patisiran and vutrisiran in patients with transthyretin cardiac amyloidosis: a network meta-analysis (HEART FAILURE 2025) - No abstract available

Retrospective data • Cardiac Amyloidosis • Cardiovascular

Patisiran Treatment in the Brazilian Subpopulation of the Phase 3 APOLLO-B Study in Transthyretin Amyloidosis with Cardiomyopathy: Post Hoc Analysis. (PubMed, Arq Bras Cardiol) - P3 | "Perugini grade improved in 11/18 (61.1%) and 0/10 evaluable patients with patisiran and placebo, respectively. There were no deaths in the patisiran group vs. 3 in the placebo group."

Biomarker • Clinical • Journal • P3 data • Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

A scientometric study on research characteristics and trends of amyloidosis involving the oral cavity. (PubMed, J Dent Sci) - "The trend of drug aspect, e.g. prednisone, colchicine, corticosteroid, doxorubicin, and vincristine before 2015 has changed to monoclonal antibody, daratumumab, tafamidis, proteasome inhibitor, carfilzomib, ixazomib, patisiran, pomalidomide, diflunisal, and doxycycline. Herein, we highlight the awareness of early diagnosis and improve the access to care for amyloidosis, since oral involvement frequently constitutes the first sign of this disease. This scientometric study elucidated the current scenario and research trends of amyloidosis, underpinning that stomatologists can play roles in providing early recognition and timely diagnosis of amyloidosis when it involved the oral cavity."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Hematological Malignancies • Multiple Myeloma • Oncology

Etiological Treatment of Cardiac Amyloidosis: Standard of Care and Future Directions. (PubMed, Curr Heart Fail Rep) - "The standard of care for ATTR-CA include agents capable of selectively stabilizing the precursor protein (e.g., tafamidis), whereas the plasma cell clone is the main target of chemotherapy for AL-CA...Recent data from ATTRibute-CM led to the approval of acoramidis, whereas patisiran received refusal based on the APOLLO-B trial. Novel CRISPR-Cas9-based drugs (i.e., NTLA-2001) hold great potential in the setting of ATTR-CA...However, the investigation of monoclonal antibodies targeting misfolded ATTR (e.g., PRX004, NI301A) or AL (e.g., birtamimab, anselamimab) has led to encouraging results. Various cutting-edge strategies are being tested for treatment of CA and may change the prognostic landscape of this condition in the next years."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Hematological Disorders

The Fomivirsen, Patisiran, and Givosiran Odyssey: How the Success Stories May Pave the Way for Future Clinical Translation of Nucleic Acid Drugs. (PubMed, BioDrugs) - "Givosiran (Givlaari; Alnylam) further revolutionized the field with a carrier-free, targeted platform, utilizing N-Acetylgalactosamine (GalNAc)-siRNA conjugates to enable efficient delivery, expanding therapeutic applications beyond rare genetic disorders to more common conditions such as hyperlipidemia and hypertension. In this review paper, we highlight the evolution of nucleic acid-based drug development, focusing on the pioneering agents fomivirsen, patisiran, and givosiran, and discuss the ongoing challenges in advancing these therapeutics and vaccines."

Journal • Cardiovascular • Dyslipidemia • Genetic Disorders • Hypertension

IMPROVEMENT IN MEASURES OF QUALITY OF LIFE AMONG PATIENTS RECEIVING TARGETTED THERAPY FOR ATTR AMYLOIDOSIS: A META-ANALYSIS OF DATA FROM RANDOMIZED CONTROLLED TRIALS - Shubhashis Saha (ACC 2025) - "Background: Novel drugs like patisiran, vutrisiran, tafamidis, acoramidis, eplontersen, and inotersen reduce the synthesis and deposition of TTR amyloid fibrils in patients with cardiac amyloidosis. Contemporary drugs for cardiac amyloidosis improved quality of life and 6MWT, while having a good safety profile. Although they are usually classified as secondary outcomes in many clinical trials, these improvements would be more relevant to the patients in short to medium term."

HEOR • Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

LACK OF IMPROVEMENT IN CARDIAC FUNCTION AMONG PATIENTS RECEIVING TARGETTED THERAPY FOR ATTR AMYLOIDOSIS: A META-ANALYSIS OF DATA FROM RANDOMIZED CONTROLLED TRIALS - Revati Varma (ACC 2025) - "Background: Novel drugs like patisiran, vutrisiran, tafamidis, acoramidis, eplontersen, and inotersen reduce the synthesis and deposition of TTR amyloid fibrils in patients with cardiac amyloidosis (CA). Contemporary drugs for CA did not result in changes in the cardiac structure on echocardiographic parameters while having a good safety profile."

Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

NANOTECHNOLOGY TO TREAT TRANSTHYRETIN MEDIATED CARDIAC AMYLOIDOSIS - Arafat Farooqui (ACC 2025) - "Random effects model was employed when there was significant heterogeneity (>40%, as assessed by I-squared). Four RCTs were finalized (n=1556; RNAi: 819, placebo: 737) that studied Patisiran (371) and Vutrisiran (448). Pooled analysis showed that RNAi molecules improved the echocardiographic parameters of study population with decrease in cardiac biomarkers and improvement in overall mortality in TTR-mediated cardiac amyloidosis."

Amyloidosis • Cardiac Amyloidosis • Cardiovascular

CARDIOVASCULAR OUTCOMES OF TARGETED THERAPIES FOR TRANSTHYRETIN-ASSOCIATED AMYLOID CARDIOMYOPATHY - Sammudeen Ibrahim (ACC 2025) - "Our study highlights the efficacy of tafamidis, vutrisiran, acoramidis, and diflunisal in significantly improving all-cause mortality, OHT, and CV hospitalizations in patients with ATTR-CM. Conversely, patisiran did not demonstrate significant benefits on the evaluated outcomes."

Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

GEOGRAPHIC DISPARITIES IN CARDIAC AMYLOIDOSIS PRESCRIBING PATTERNS: INSIGHTS FROM EPIC COSMOS - Mirza S. Khan (ACC 2025) - "Medications included novel amyloid therapies tafamidis, vutrisiran, patisiran, eplontersen, inotersen and diflunisal. The highest prescription rates for cardiac amyloidosis therapies were in the Northeast U.S., known to have a high density of dedicated amyloidosis centers. Our findings underscore the need for efforts to improve recognition and diagnosis of cardiac amyloidosis and improve treatment access in underserved regions."

Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Congestive Heart Failure • Heart Failure

Decreased amyloid deposits after introduction of patisiran in ATTRv patients - Evaluation by biopsy, PET, and PYP scintigraphy (JSNE 2025) - No abstract available

Biopsy • Clinical • Gene Therapies • Pain

Precision medicine in the diagnostics and treatment of cardiomyopathies : State of the art (PubMed, Herz) - "Mavacamten treats left ventricular outflow tract (LVOT) obstruction in hypertrophic CMP, while tafamidis and RNA-based treatment, such as patisiran and vutrisiran specifically affect transthyretin-mediated amyloidosis. Artificial intelligence (AI) is pivotal in precision medicine where AI-assisted analyses enhance the diagnosis of subclinical diseases, optimize imaging modalities and accelerate the development of new treatment approaches. The ESC guidelines are an important milestone in the care of patients with CMP, while also emphasizing the need for further research and scientific ethical discussions, especially with respect to AI and innovative forms of treatment."

Journal • Review • Amyloidosis • Cardiomyopathy • Cardiovascular • Gene Therapies

Formulation and Characterization of Novel Ionizable and Cationic Lipid Nanoparticles for the Delivery of Splice-Switching Oligonucleotides. (PubMed, Adv Mater) - "An LNP is identified that outperforms Onpattro lipid composition using lipid components and molar ratios which differ from the gold standard clinical LNPs...The importance of stabilizer choice for the LNP function is demonstrated and super-resolution microscopy highlights the complexity of the delivery mechanisms, where lysosomal swelling for the majority of LNPs is observed. This study highlights the importance of advanced characterization for the rational design of LNPs to enable the study of structure-function relationships."

Journal • Hematological Disorders

RNAi Therapeutics for hATTR Amyloidosis: A Comprehensive Single Arm Meta-Analysis of Clinical Outcomes and Treatment Efficacy (AAN 2025) - "Objective:The primary objective of this single-arm meta-analysis is to comprehensively evaluate the efficacy and clinical outcomes of RNA interference (RNAi) therapies, specifically patisiran and vutrisiran, in the treatment of hereditary transthyretin amyloidosis (hATTR) with neurologic involvement.Background:New RNA interference (RNAi) therapies, particularly patisiran and vutrisiran, represent a groundbreaking approach in the management of Hereditary Transthyretin Amyloidosis (hATTR). This meta-analysis demonstrates that RNA interference drugs significantly slow progression of disease, substantially improves neurologic symptoms and quality of life, with a favorable safety profile. These findings support its use as a valuable treatment option for hereditary transthyretin amyloidosis. Further research is needed to assess long-term outcomes and comparative effectiveness."

Clinical data • Retrospective data • Amyloidosis • Cardiac Amyloidosis • Pain

RNAi-based Therapies for Hereditary Transthyretin Amyloidosis with Polyneuropathy: A Meta-analysis of Randomized Clinical Trials (AAN 2025) - "Subgroup analysis is performed based on individual RNAi drugs.We included 5 trials involving 595 patients received Patisiran, Eplontersen, Inotersen, or Vutisiran. Our results suggest that RNAi-based therapies are promising for hATTR with polyneuropathy treatment, showing improvements in neurological function, quality of life, and an acceptable safety profile. However, evidence is limited, with heterogeneity in long-term safety and effectiveness across studies. Further randomized trials are needed to clarify the role of RNAi therapeutics and optimize patient outcomes."

Retrospective data • Amyloidosis • Cardiac Amyloidosis • Genetic Disorders • Pain

Efficacy of Pharmacological Interventions for Transthyretin Familial Amyloid Polyneuropathy (TTR-FAP): A Systematic Review and Network Meta-Analysis (AAN 2025) - "Patisiran and Inotersen demonstrated superior efficacy with significant results, while Vutrisiran and Diflunisal also showed notable outcomes. In contrast, Tafamidis did not yield significant results. Further research is needed to confirm these findings."

Retrospective data • Review • Amyloidosis • CNS Disorders • Diabetic Neuropathy • Pain

Complete remission after patisiran treatment in a patient with nephrotic syndrome secondary to hereditary transthyretin amyloidosis (ATTR). (PubMed, Amyloid) - No abstract available

Journal • Amyloidosis • Cardiac Amyloidosis • Glomerulonephritis • Nephrology • Renal Disease

An Industry Perspective on the Use of Novel Excipients in Lipid Nanoparticles-Nonclinical Considerations. (PubMed, Int J Toxicol) - "Three case studies (Onpattro®, Comirnaty®, and SpikeVax®) highlight that specific assessments may differ depending on the encapsulated modality, the intended use (e.g., therapeutic versus preventative vaccine), dose, and frequency of dosing. Proactive alignment with regulatory authorities will be critical in this context, especially as new approaches are proposed. Guidance documents may need to be revised or created as more experience is acquired to reflect the unique considerations for these novel excipients."

Journal

Therapeutic effect of TTR siRNA on hereditary transthyretin amyloidosis (ATTRv) nephropathy. (PubMed, Amyloid) - "Notably, longitudinal data showed that TTR siRNA therapeutics reduced proteinuria and increased serum protein, while none of the new treatments could demonstrate a significant improvement in the slope of eGFR decline. We demonstrated that TTR siRNA therapeutics represent potential candidates for ATTRv nephropathy, despite the fact that their use has been limited to neurological symptoms to date."

Journal • Amyloidosis • Cardiac Amyloidosis • Renal Disease

Phenotype variability and therapeutic response to Patisiran in patients with hereditary transthyretin amyloidosis: a Belgian real-world experience. (PubMed, Acta Clin Belg) - "Currently, several disease-modifying treatments for hATTRv are available in Belgium including the TTR stabilizer tafamidis and TTR mRNA silencers patisiran and vutrisiran. The cases also highlight the importance of red flags recognition to allow early diagnosis and treatment to prevent further disease progression. Due to the multisystemic nature of the disease and its heterogeneous clinical presentation, close collaboration between neurologists and cardiologists is highly recommended, ideally within a multidisciplinary amyloidosis team, to provide holistic care in hATTRv patients."

Journal • Real-world evidence • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Gastrointestinal Disorder • Pain

Patisiran in ATTRv amyloidosis with polyneuropathy: "PatisiranItaly" multicenter observational study. (PubMed, J Neurol) - "Patisiran can be considered a valid therapeutic option for the management of patients with ATTRv amyloidosis. Considering its mechanism of action, similar outcomes could also be expected with the wider utilization of newly approved gene silencers for ATTRv therapy, such as vutrisiran."

Journal • Observational data • Amyloidosis • Cardiac Amyloidosis • CNS Disorders • Diabetic Neuropathy • Pain

Alnylam Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Highlights Recent Period Progress (Businesswire) - "Achieved global net product revenues for ONPATTRO and AMVUTTRA for the fourth quarter of $56 million and $287 million, respectively, and $343 million combined, representing 35% total TTR growth compared to Q4 2023, and full year 2024 revenues of $253 million and $970 million, respectively, and $1,223 million combined, representing 34% total TTR growth compared to full year 2023...Achieved global net product revenues for GIVLAARI and OXLUMO for the fourth quarter of $65 million and $44 million, respectively, and $108 million combined, representing 18% total Rare growth compared to Q4 2023, and full year 2024 revenues of $256 million and $167 million, respectively, and $423 million combined, representing 29% total Rare growth compared to full year 2023."

Commercial • Amyloidosis • Genetic Disorders • Rare Diseases • Renal Calculi • Renal Disease

Development, opportunities, and challenges of siRNA nucleic acid drugs. (PubMed, Mol Ther Nucleic Acids) - "The US Food and Drug Administration has approved six siRNA drugs in recent years: patisiran, givosiran, lumasiran, vutrisiran, inclisiran, and nedosiran. This review summarizes the history of siRNA drug development and the mechanisms of action, with a focus on the drug targets, indications, and key clinical trial results to introduce the status of both marketed drugs and those currently in clinical trials. Additionally, this review provides a brief analysis of several key stages of the commercialization process of siRNA drugs."

Journal • Review

Worsening of Heart Failure in Outpatients With Transthyretin Amyloidosis and Cardiomyopathy in the APOLLO-B Trial. (PubMed, J Am Coll Cardiol) - P3 | "During APOLLO-B, outpatient worsening HF in patients with transthyretin amyloidosis with cardiomyopathy was frequent, prognostic, and reduced by patisiran."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy: A Randomized Clinical Trial With Open-Label Extension. (PubMed, JAMA Neurol) - P3 | "These results highlight the importance of initiating early treatment for hATTR and the potential of RNAi therapeutics in medicine. ClinicalTrials.gov Identifier: NCT02510261."

Clinical • Journal • Amyloidosis • Cardiac Amyloidosis • CNS Disorders • Diabetic Neuropathy • Pain