ReviewMolecular diagnosis & therapy2020
Leading RNA Interference Therapeutics Part 2: Silencing Delta-Aminolevulinic Acid Synthase 1, with a Focus on Givosiran.
Review in Molecular diagnosis & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03338816 (ENVISION), which is not on this map. Cited by 38 papers, 2 of them syntheses that pooled it.
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.
ENVISION: A Phase 3 Randomized, Double-blind, Placebo-Controlled Multicenter Study With an Open-label Extension to Evaluate the Efficacy and Safety of Givosiran in Patients With Acute Hepatic Porphyrias
Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- C16-siRNAs in Focus: Development of ALN-APP, a Promising RNAi-Based Therapeutic for Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Pathogenesis and clinical management of liver damage in porphyrias: Mechanisms and therapeutic approaches.World journal of hepatology · 2025Review
- Pharmaceutical perspectives on oligonucleotide therapeutics and delivery systems.Pharmacological reviews · 2025Review
- Recent Advances in Immune Regulation by Targeting Dendritic Cells using Small Interfering RNAs.Current molecular medicine · 2025Review
- Advancements in clinical RNA therapeutics: Present developments and prospective outlooks.Cell reports. Medicine · 2024Review
- Gemogenovatucel-T (Vigil): bi-shRNA plasmid-based targeted immunotherapy.Future oncology (London, England) · 2024Review
- A Computational Approach for Designing and Validating Small Interfering RNA against SARS-CoV-2 Variants.Current computer-aided drug design · 2024Article
- Blockage of Osteopontin-Integrin β3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Progress in circRNA-Targeted Therapy in Experimental Parkinson's Disease.Pharmaceutics · 2023Review
- Unleashing the potential of catalytic RNAs to combat mis-spliced transcripts.Frontiers in bioengineering and biotechnology · 2023Review
- Review
- Harnessing the Therapeutic Potential of Biomacromolecules through Intracellular Delivery of Nucleic Acids, Peptides, and Proteins.Advanced healthcare materials · 2022Review
- Current Advances in RNA Therapeutics for Human Diseases.International journal of molecular sciences · 2022Review
- Deliver the promise: RNAs as a new class of molecular entities for therapy and vaccination.Pharmacology & therapeutics · 2022Review
- Recent Advances in RNA Therapy and Its Carriers to Treat the Single-Gene Neurological Disorders.Biomedicines · 2022Review
- Effect of FLOT2 Gene Expression on Invasion and Metastasis of Colorectal Cancer and Its Molecular Mechanism under Nanotechnology and RNA Interference.BioMed research international · 2022Article
- Spotlight on Givosiran as a Treatment Option for Adults with Acute Hepatic Porphyria: Design, Development, and Place in Therapy.Drug design, development and therapy · 2022Review
- MicroRNAs in the Regulation of Solute Carrier Proteins Behind Xenobiotic and Nutrient Transport in Cells.Frontiers in molecular biosciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In November 2019 givosiran became the second small interfering RNA (siRNA)-based drug to receive US Food and Drug Administration (FDA) approval, it has been developed for the treatment of acute intermittent porphyria (AIP), a disorder characterized by life-threatening acute neurovisceral attacks. The porphyrias are a group of disorders in which enzymatic deficiencies in heme production lead to toxic accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), which are involved in the neurovisceral attacks. Givosiran acts as a conventional siRNA to trigger RNA interference (RNAi)-mediated gene silencing on delta-ALA synthase 1 (ALAS1), thus returning ALA and PBG metabolites to the physiological level to attenuate further neurotoxicity. Givosiran makes use of a new hepatic-delivery system that conjugates three GalNac (N-acetylgalactosamine) molecules to the siRNA passenger strand. GalNac binds to the liver asialoglycoprotein receptor, favoring the internalization of these GalNac-conjugated siRNAs into the hepatic cells. In a phase I study, subcutaneous monthly administration of givosiran 2.5 mg/kg reduced > 90% of ALA and PBG content. This siRNA is being analyzed in ENVISION (NCT03338816), a phase III, multicenter, placebo-controlled randomized controlled trial. In preliminary results, givosiran achieved clinical endpoints for AIP, reducing urinary ALA levels, and presented a safety profile that enabled further drug development. The clinical performance of givosiran revealed that suppression of ALAS1 by GalNac-decorated siRNAs represents an additional approach for the treatment of patients with AIP that manifests recurrent acute neurovisceral attacks.
Indexed as
Identifiers
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.