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

Neuropathy Progression in Variant Transthyretin Amyloidosis: Comparison Between TTR Stabilizers and Gene Silencer Therapies. (PubMed, Muscle Nerve) - "In this cohort, patisiran attenuated neuropathy progression in patients who had deteriorated despite tafamidis. These findings highlight the importance of ongoing clinical monitoring to guide timely treatment optimization."

Journal • Amyloidosis • Cardiac Amyloidosis • Pain

Integrating Artificial Intelligence with Emerging Pharmaceutical Technologies: Current Progress, Clinical Translation, and Future Challenges. (PubMed, Int J Mol Sci) - "Nanotechnology is advancing drug delivery through the use of nanoparticle systems, such as Doxil® and Onpattro®. Obstacles remain, including regulatory constraints, ethical considerations, data quality limitations, and the need for stronger validation, although ongoing funding, interdisciplinary collaboration, and evolving regulatory frameworks may support further development. Overall, these technologies show meaningful potential to shorten development time and improve treatment safety, although further prospective validation is required before realizing this potential at scale."

Journal • Review • Hepatology • Liver Failure

Molecular imaging of TTR amyloidosis: New data. (PubMed, Hell J Nucl Med) - "This narrative review synthesizes recent data on molecular imaging, emphasizing the central role of nuclear medicine physicians in applying multimodality diagnostic algorithms, recognizing typical and equivocal scan patterns. It further explores emerging roles for quantitative SPECT/CT and amyloid PET tracers in monitoring response to disease modifying therapies, including tetramer stabilizers (tafamidis, acoramidis), RNA interference silencers (vutrisiran, patisiran), and investigational fibril targeting antibodies and gene editing strategies, underscoring a shift from purely diagnostic imaging toward dynamic treatment monitoring in ATTR CM."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Congestive Heart Failure • Gastrointestinal Disorder • Heart Failure

Cardiac presentation and treatment response by sex in patients with transthyretin amyloidosis: pooled analysis of vutrisiran and patisiran phase 3 studies (ESC 2026) - "In this pooled analysis of ATTR clinical studies, some baseline findings suggest more advanced disease in females vs males, despite relatively preserved myocardial function. Regardless of baseline differences, the pooled treatment effect of vutrisiran/patisiran versus placebo was generally consistent across sexes, supporting their potential for broad therapeutic applicability. Additional efforts are needed to improve earlier recognition of ATTR in women."

P3 data • Retrospective data • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Which therapy performs best across clinical domains in transthyretin amyloid cardiomyopathy? a frequentist network meta-analysis (ESC 2026) - "Patisiran showed favourable but less consistent signals across domains. Seven trials, including 2,494 patients, were analysed. No therapy consistently led all endpoints, supporting domain-specific heterogeneity. Vutrisiran showed the strongest biomarker and functional profile, with greater reductions in troponin I (SMD -3.65, 95% CI -3.90 to -3.40) and N-terminal pro-B-type natriuretic peptide (SMD -0.55, 95% CI -0.71 to -0.39), together with the largest improvement in 6-minute walk distance (SMD 0.53, 95% CI 0.24 to 0.82)."

Retrospective data • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Long-term efficacy of vutrisiran in patients with variant transthyretin amyloid cardiomyopathy (ESC 2026) - "Of these, 10 patients who initiated vutrisiran therapy were assigned to the vutrisiran-naïve group, whereas 8 patients who switched from patisiran to vutrisiran were assigned to the vutrisiran-switch group. Vutrisiran demonstrated favorable real-world clinical efficacy in patients with ATTRv-CM in our cohort."

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

The Promise and Pursuit of MicroRNAs for Cancer Treatment. (PubMed, Biomolecules) - "Additional modifications that enabled microRNA mimics to cross cell membranes include substituting uracil with 5-fluorouracil. Lessons from an siRNA therapeutic called Patisiran offer a roadmap for future success for microRNAs in cancer. This review provides a historical perspective of the continuing evolution of microRNA mimics for cancer treatment."

Journal • Review • Oncology

Bioactive lipid-derived nanoparticles for RNA delivery. (PubMed, Mater Today (Kidlington)) - "Lipid nanoparticles (LNPs) have emerged as the most widely used and clinically validated platform for delivering RNAs, including small interfering RNA (siRNA) and messenger RNA (mRNA), as exemplified by the FDA approvals of Onpattro, Comirnaty, Spikevax, and mRESVIA. We also discuss the structure-activity relationship of these bioactive lipids and overview their corresponding LNPs for specific biomedical applications. We further provide perspectives on the challenges and opportunities in translating bioactive lipid-derived LNPs into next-generation RNA nanomedicines."

Journal • Immunology

Disease-Modifying Therapies for Transthyretin Amyloid Cardiomyopathy: Current Evidence and Emerging Strategies. (PubMed, J Clin Med Res) - "This narrative review synthesizes current evidence on pharmacologic strategies for ATTR-CM, including transthyretin stabilizers such as tafamidis and acoramidis, gene-silencing therapies including patisiran, vutrisiran, and eplontersen, fibril disruptors, and emerging amyloid-depleting monoclonal antibodies and gene-editing approaches. The convergence of early diagnosis through improved imaging and biomarker strategies with targeted therapeutics has substantially changed the outlook for patients with a previously untreatable disease. Future directions emphasize combination therapies, biomarker-guided treatment selection, and precision medicine approaches tailored to disease genotype and phenotype."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure

SiaRNA: a siamese neural network with bidirectional cross-attention for pairwise siRNA-mRNA efficacy prediction. (PubMed, Front Bioinform) - "The results prove SiaRNA's potential as a reliable and biologically accurate framework to guide siRNA design and improve therapeutic outcomes. On performing a case study using Patisiran siRNA and its target transthyretin (TTR) mRNA, an efficacy value of 0.7134 was observed indicating that our model can successfully identify therapeutically effective targets."

Journal

Emerging trends in nanomedicine: The role of RNAi-based therapies and onpattro's clinical journey. (PubMed, Iran J Basic Med Sci) - "Recent advances in mRNA vaccines, CRISPR-based gene editing, and stimuli-responsive nanoparticles are addressing these challenges, supported by growing clinical case studies and real-world data. This review highlights Onpattro's clinical development, compares delivery platforms, discusses translational challenges, and examines emerging technologies that will guide the next generation of RNAi nanomedicines in personalized therapy."

Journal • Review • Amyloidosis

Clinical outcomes with vutrisiran in transthyretin amyloidosis: a systematic review and meta-analysis of randomized trials. (PubMed, Glob Cardiol Sci Pract) - "Comparator participants received placebo, patisiran (an active reference comparator in HELIOS-A), or external placebo from the APOLLO trial. It reduced fall risk without increasing adverse events, indicating a favourable safety profile. Larger, long-term RCTs are needed to confirm survival and functional benefits."

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

Real-world effectiveness and clinical predictors of response to first-generation TTR silencers in variant ATTR amyloidosis with polyneuropathy. (PubMed, Sci Rep) - "Total responders had higher baseline CMAP amplitudes (p = 0.045), while baseline neurophysiological measures showed modest discriminatory capacity overall, with electrochemical skin conductance providing the strongest signal...Compared with inotersen, patisiran showed a higher total response rate (59.3% vs. 23.5%), slower NIS progression (median + 0.31 vs. +4.00 points/year; p = 0.011), and greater treatment persistence (log-rank p = 0.0005)...Baseline neurological preservation, particularly motor and small-fiber measures, may help identify patients more likely to benefit from treatment. However, these findings should be interpreted with caution due to the limited sample-size and the observational nature of the study."

Journal • Real-world evidence • Amyloidosis • Cardiac Amyloidosis • CNS Disorders • Pain

Disease-Modifying Therapies for Hereditary Transthyretin Amyloidosis with Polyneuropathy: Current Status and Future Perspectives. (PubMed, Neurol Ther) - "These therapies include TTR stabilizers, such as tafamidis, diflunisal, and acoramidis, as well as RNA-silencing agents, such as patisiran, vutrisiran, inotersen, and eplontersen, which reduce hepatic production of TTR and slow disease progression...Emerging gene-editing approaches, including CRISPR-based therapies like NTLA-2001, may provide a one-time treatment and long-term disease control, representing a promising future direction for managing ATTRv-PN...These include high treatment costs, limited global accessibility, uncertainty regarding optimal treatment selection and sequencing, and the need for long-term real-world, patient-centered outcome data. This review summarizes current disease-modifying therapies for ATTRv-PN, compares their mechanisms and clinical evidence, and discusses unmet needs and future research directions, with the aim of providing a practical and comprehensive overview for clinicians treating patients with ATTRv-PN."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Developmental Disorders • Gene Therapies • Pain • Transplantation

Guidelines for the management of hereditary ATTR amyloidosis 2026. (PubMed, Amyloid) - "Tafamidis and vutrisiran are indicated for both polyneuropathy (ATTRv-PN) and cardiomyopathy (ATTR-CM), patisiran, eplontersen and diflunisal are for ATTRv-PN only, and acoramidis is for ATTR-CM only. The currently available disease-modifying therapeutics have a limited effect on central nervous system (CNS) and ocular manifestations since they target either blood circulating TTR from the liver or ATTR amyloid fibrils misfolding in the blood and depositing in systemic (non-CNS, non-ocular) tissues. Development of disease-modifying therapies for CNS and ocular ATTR amyloidosis is an urgent unmet medical need."

Journal • Review • Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders • Developmental Disorders • Pain

Advancing siRNA Therapeutics with Pharmacometrics: A Review of Modeling Approaches and Clinical Applications. (PubMed, Curr Gene Ther) - "Since the FDA's first approval of patisiran in 2018, the field has expanded rapidly, with eight approved drugs and numerous clinical candidates...This review also discusses how quantitative pharmacology addresses developmental challenges, including first-in-human dose selection, optimal dosing intervals, organ impairment effects, and interindividual variability. This pharmacometric perspective provides a quantitative framework for rational development of safe and effective siRNA therapeutics across diverse patient populations."

First-in-human • Journal • ASGR • MUC4

Microfluidic Synthesis of miR-10a Antisense Oligonucleotides-Loaded LNP Combined with Cisplatin for Colorectal Cancer Therapy. (PubMed, Anticancer Agents Med Chem) - "LNPs/miR-10a-AMOs can efficiently deliver AMOs and represent a potential strategy for treating CRC. By enhancing the sensitivity of tumors to cisplatin, this system improved the therapeutic effect while ensuring the safety of normal cells. This provides a new strategy with translational potential for the precise treatment of CRC."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CASP3

Multicenter cohort analysis of cardiac amyloidosis patients treated with heart transplant. (PubMed, Rev Esp Cardiol (Engl Ed)) - "HT is an effective treatment for carefully selected patients with cardiac amyloidosis, with comparable unadjusted survival between AL and ATTR. These findings warrant confirmation in prospective studies."

Clinical • Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Hematological Disorders • Infectious Disease • Pain • Septic Shock • Transplantation

Identification of a cell subpopulation with different response to lipid nanoparticles and effect of protein corona on uptake and transfection. (PubMed, Mater Today Bio) - "Here, we used LNPs of composition comparable to Onpattro and we analyzed their uptake, transfection efficiency and effects in thousands individual HeLa cells by flow cytometry...Overall, these results indicate that the response to LNPs is highly heterogeneous, and some cells within the cell population are more sensitive to the LNPs. Furthermore, LNP uptake and transfection are strongly affected by the modifications LNPs encounter upon dispersion in biological environments."

Journal

Small Non-Coding RNA in Breast Cancer Therapy: Yin-Yang. (PubMed, Mini Rev Med Chem) - "Furthermore, the potential use of small noncoding RNAs such as Patisiran and Miravirsen in cancer treatment has been promising. However, our understanding of miRNA and siRNA is limited, and their therapeutic uses are currently restricted by challenges related to delivery, stability, and offtarget activity. Ongoing research aimed at overcoming these limitations may enable RNA-based therapeutics to become effective tools for the diagnosis and treatment of breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor

Clinical course after cardiac resynchronization therapy in transthyretin amyloid cardiomyopathy receiving disease-modifying therapy. (PubMed, Heart Vessels) - "We aimed to describe the clinical, electrocardiographic, echocardiographic, and long-term outcomes of ATTR-CM patients treated with CRT while receiving tafamidis or patisiran. Because the effects of CRT could not be disentangled from those of concomitant DMT, these findings should be interpreted as descriptive and hypothesis-generating. This study does not qualify as a clinical trial, and it is a retrospective analysis and not classified as an interventional investigation."

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

Pharmacological Interventions for Hereditary Transthyretin-Related Amyloidosis With Polyneuropathy: Systematic Review and Network Meta-Analysis. (PubMed, Eur J Neurol) - "Gene-silencing therapies were more efficacious, although these findings should be regarded as hypothesis-generating given the scarcity of data, lack of head-to-head trials, and clinical heterogeneity across trials."

Journal • Retrospective data • Review • Amyloidosis • CNS Disorders • Pain

Deep Phenotyping of F64L Mutation in a Multicentric Cohort of Patisiran-Treated Hereditary Transthyretin Amyloidosis Patients (Patisiranitaly). (PubMed, Eur J Neurol) - "F64L is characterized by predominant neurologic involvement and milder cardiac involvement in this Patisiran-treated cohort. Mutation-specific diagnostic and follow-up strategies are essential to capture its natural history and treatment response."

Journal • Amyloidosis • Cardiac Amyloidosis

First-Generation TTR Silencing Therapies in Hereditary Transthyretin Amyloidosis With Polyneuropathy: Real-World Insights From a German Single-Referral Center. (PubMed, Eur J Neurol) - "Our findings confirm long-term treatment with TTR silencers in a real-world setting is safe, consistently reducing serum TTR levels, stabilizing neurologic symptoms, cardiac and renal functions, and nutritional parameters."

Journal • Real-world evidence • Amyloidosis • Cardiac Amyloidosis • CNS Disorders • Hematological Disorders • Pain • Thrombocytopenia

Lung surfactants as a component of lipid nanoparticles for pulmonary mRNA delivery. (PubMed, bioRxiv) - "The resulting lung surfactant-enhanced LNPs (Surf-LNPs) exhibited substantial improvements in particle assembly, yielding an order of magnitude higher particle concentration at equivalent input conditions compared to conventional (Onpattro-like) LNP formulations. In vivo evaluation following intranasal administration further revealed enhanced mCherry expression in the lungs of mice treated with Surf-LNPs compared to conventional LNPs. Ultimately, these findings establish lung surfactant incorporation as a simple yet powerful formulation strategy to improve pulmonary gene delivery using LNPs, with the potential to significantly advance the translation of inhaled nucleic acid therapeutics."

Journal • Genetic Disorders