Biology:Givosiran
| Clinical data | |
|---|---|
| Trade names | Givlaari |
| AHFS/Drugs.com | Monograph |
| License data | |
| 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.[2][5][6][7] Givosiran is a small interfering RNA (siRNA) directed towards delta-aminolevulinate synthase 1 (ALAS1),[8] an important enzyme in the production of heme.
The most common side effects include nausea and injection site reactions.[7]
The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[9]
Medical uses
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).[2][6]
History
In November 2019, givosiran was approved in the United States for the treatment of adults with acute hepatic porphyria (AHP).[6][10]
Efficacy was evaluated in ENVISION (NCT03338816), a randomized, double‑blind, placebo‑controlled, multinational trial enrolling 94 participants with acute hepatic porphyria.[7] 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.[7] 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.[6] Participants who received givosiran experienced 70% fewer porphyria attacks compared to patients receiving a placebo.[6]
The U.S. Food and Drug Administration (FDA) granted the application for givosiran breakthrough therapy designation, priority review designation, and orphan drug designation.[6][7] The FDA granted the approval of Givlaari to Alnylam Pharmaceuticals.[6]
References
- ↑ "Summary Basis of Decision (SBD) for Givlaari". 23 October 2014. https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00514&lang=en.
- ↑ 2.0 2.1 2.2 "Givlaari- givosiran sodium injection, solution". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=167e663c-11e1-497b-a3fc-951d65d58eaa.
- ↑ "Givlaari EPAR". 29 January 2020. https://www.ema.europa.eu/en/medicines/human/EPAR/givlaari.
- ↑ "Givlaari Product information". https://ec.europa.eu/health/documents/community-register/html/h1428.htm.
- ↑ "Givosiran: A Review in Acute Hepatic Porphyria". Drugs 81 (7): 841–848. May 2021. doi:10.1007/s40265-021-01511-3. PMID 33871817.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 "FDA approves first treatment for inherited rare disease". U.S. Food and Drug Administration (FDA) (Press release). 20 November 2019. Archived from the original on 21 November 2019. Retrieved 20 November 2019.
This article incorporates text from this source, which is in the public domain.
- ↑ 7.0 7.1 7.2 7.3 7.4 "FDA approves givosiran for acute hepatic porphyria". 20 November 2019. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-givosiran-acute-hepatic-porphyria. 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". 31 December 2019. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019.
- ↑ "Drug Trials Snapshots: Givlaari". 20 November 2019. http://www.fda.gov/drugs/drug-trials-snapshots-givlaari. This article incorporates text from this source, which is in the public domain.
External links
- "Givosiran". Drug Information Portal. U.S. National Library of Medicine (NLM). https://druginfo.nlm.nih.gov/drugportal/name/givosiran.
- 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
 |
