Givosiran
| Clinical data | |
|---|---|
| Trade names | Givlaari |
| AHFS/Drugs.com | Monograph |
| License data | |
| Pregnancy category |
|
| Routes of administration | Subcutaneous |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| UNII | |
| KEGG | |
| Chemical and physical data | |
| Formula | C524H694F16N173O316P43S6 |
| Molar mass | 16300.42 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
Givosiran, sold under the brand name Givlaari, is a medication used for the treatment of adults with acute hepatic porphyria.[3][6][7][8] Givosiran is a small interfering RNA (siRNA) directed towards delta-aminolevulinate synthase 1 (ALAS1),[9] an important enzyme in the production of heme.
The most common side effects include nausea and injection site reactions.[8]
The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[10]
Medical uses
[edit]Givosiran is indicated for the treatment of adults with acute hepatic porphyria, a genetic disorder resulting in the buildup of toxic porphyrin molecules which are formed during the production of heme (which helps bind oxygen in the blood).[3][7]
History
[edit]In November 2019, givosiran was approved in the United States for the treatment of adults with acute hepatic porphyria (AHP).[7][11]
Efficacy was evaluated in ENVISION (NCT03338816), a randomized, double‑blind, placebo‑controlled, multinational trial enrolling 94 participants with acute hepatic porphyria.[8] Participants were randomized (1:1) to receive once monthly subcutaneous injections of givosiran 2.5 mg/kg or placebo during a six‑month double‑blind period.[8] The performance of givosiran was measured by the rate of porphyria attacks that required hospitalizations, urgent health care visits or intravenous infusion of hemin at home.[7] Participants who received givosiran experienced 70% fewer porphyria attacks compared to patients receiving a placebo.[7]
The U.S. Food and Drug Administration (FDA) granted the application for givosiran breakthrough therapy designation, priority review designation, and orphan drug designation.[7][8] The FDA granted the approval of Givlaari to Alnylam Pharmaceuticals.[7]
References
[edit]- ^ a b "Givlaari APMDS". Therapeutic Goods Administration (TGA). 15 December 2023. Archived from the original on 2 January 2024. Retrieved 7 March 2024.
- ^ "Summary Basis of Decision (SBD) for Givlaari". Health Canada. 23 October 2014. Archived from the original on 30 May 2022. Retrieved 29 May 2022.
- ^ a b c "Givlaari- givosiran sodium injection, solution". DailyMed. Archived from the original on 8 February 2022. Retrieved 7 February 2022.
- ^ "Givlaari EPAR". European Medicines Agency. 29 January 2020. Archived from the original on 12 November 2021. Retrieved 4 March 2023.
- ^ "Givlaari Product information". Union Register of medicinal products. Archived from the original on 5 March 2023. Retrieved 3 March 2023.
- ^ Syed YY (May 2021). "Givosiran: A Review in Acute Hepatic Porphyria". Drugs. 81 (7): 841–848. doi:10.1007/s40265-021-01511-3. PMID 33871817. S2CID 233292573.
- ^ a b c d e f g This article incorporates text from this source, which is in the public domain.
- ^ a b c d e This article incorporates text from this source, which is in the public domain.
- ^ Balwani M, Sardh E, et al.; ENVISION Investigators. Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria. N Engl J Med. 2020 Jun 11;382(24):2289-2301. doi: 10.1056/NEJMoa1913147. PMID 32521132.
- ^ "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Archived from the original on 18 January 2024. Retrieved 15 September 2020.
- ^ This article incorporates text from this source, which is in the public domain.
External links
[edit]- Clinical trial number NCT03338816 for "ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)" at ClinicalTrials.gov
