ArticleNature medicine2015
An RNAi therapeutic targeting antithrombin to rebalance the coagulation system and promote hemostasis in hemophilia.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03619863 (A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment for People With Hemophilia), which is not on this map. Cited by 144 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment for People With Hemophilia
Who cites it
144 citing papers in PubMed, 291 citations in OpenAlex.
- Trial
- Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B.Blood advances · 2025Trial
- Trial
- Clinical Proof of Concept for a Novel Hepatocyte-Targeting GalNAc-siRNA Conjugate.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Trial
- Toward a Platform PBPK Model to Characterize the Plasma and Tissue Disposition of Unconjugated Antisense Oligonucleotides and GalNAc-Conjugated Small Interfering RNAs in Preclinical Species and Human.Clinical pharmacology and therapeutics · 2026Article
- Current perspectives on non-factor therapies for hemophilia.International journal of hematology · 2026Review
- A computational model-powered platform to inform the development of GalNAc-conjugated siRNA therapeutics.Molecular therapy. Nucleic acids · 2026Article
- Non-factor Therapies in Hemophilia: Mechanisms, Clinical Evidence, Patient Management, and Future Perspectives.Advances in therapy · 2026Review
- Fitusiran treatment modulates the ratio between alpha- and beta-antithrombin isoforms.HemaSphere · 2026Article
- Long-Acting RNA Interference Therapies for Cardiovascular Risk Reduction: Current Evidence and Emerging Targets.Current cardiology reports · 2026Review
- Advances in nano-delivery systems for overcoming the challenges of applying siRNA drugs in tumor therapy.Asian journal of pharmaceutical sciences · 2026Review
- Challenges in Balancing Hemostasis and Thrombosis in Therapy Tailoring for Hemophilia: A Narrative Review.International journal of molecular sciences · 2026Review
- Advancements in CRISPR-basedFrontiers in genome editing · 2026Review
- Characterization of a factor VIII/immunoglobulin heavy chain μ double-knockout mouse model of hemophilia A for long-term exposure to factor VIII proteins.Research and practice in thrombosis and haemostasis · 2026Article
- How multispecific molecules are transforming pharmacotherapy.Nature reviews. Drug discovery · 2025Review
- The Mirage of Factor Equivalence: Examining the Complexities of Non-Factor Therapies in Haemophilia.Haemophilia : the official journal of the World Federation of Hemophilia · 2025Review
- Haemophilia Prophylaxis in the Age of Innovation: Exploring Opportunities for Personalized Treatment.Haemophilia : the official journal of the World Federation of Hemophilia · 2025Review
- Global Comparative Antithrombin Field Study: Impact of Laboratory Assay Variability on the Assessment of Antithrombin Activity Measurement at Fitusiran Clinical Decision-Making Points.Haemophilia : the official journal of the World Federation of Hemophilia · 2025Article
- Thrombin Generation Assay to Support Hematologists in the Era of New Hemophilia Therapies.International journal of laboratory hematology · 2025Review
- The liver-specific long noncoding RNA FAM99B inhibits ribosome biogenesis and cancer progression through cleavage of dead-box Helicase 21.Cell death & disease · 2025Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors at 5 institutions in 2 countries.
Funding
Abstract
Hemophilia A and B are inherited bleeding disorders characterized by deficiencies in procoagulant factor VIII (FVIII) or factor IX (FIX), respectively. There remains a substantial unmet medical need in hemophilia, especially in patients with inhibitory antibodies against replacement factor therapy, for novel and improved therapeutic agents that can be used prophylactically to provide effective hemostasis. Guided by reports suggesting that co-inheritance of prothrombotic mutations may ameliorate the clinical phenotype in hemophilia, we developed an RNA interference (RNAi) therapeutic (ALN-AT3) targeting antithrombin (AT) as a means to promote hemostasis in hemophilia. When administered subcutaneously, ALN-AT3 showed potent, dose-dependent, and durable reduction of AT levels in wild-type mice, mice with hemophilia A, and nonhuman primates (NHPs). In NHPs, a 50% reduction in AT levels was achieved with weekly dosing at approximately 0.125 mg/kg, and a near-complete reduction in AT levels was achieved with weekly dosing at 1.5 mg/kg. Treatment with ALN-AT3 promoted hemostasis in mouse models of hemophilia and led to improved thrombin generation in an NHP model of hemophilia A with anti-factor VIII inhibitors. This investigational compound is currently in phase 1 clinical testing in subjects with hemophilia A or B.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.