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Givosiran: First Approval

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Abstract

Givosiran (Givlaari™) is an aminolevulinate synthase 1 (ALAS1)-directed small interfering RNA (siRNA) covalently linked to a ligand to enable specific delivery of the siRNA to hepatocytes. This results in downregulation of ALAS1 mRNA and prevents accumulation of neurotoxic δ-aminolevulinic acid and porphobilinogen levels that are associated with acute porphyria attacks. Givosiran is being developed by Alnylam Pharmaceuticals for the treatment of acute hepatic porphyria (AHP). In November 2019, givosiran was approved in the USA for the treatment of adults with AHP based on the positive results from the multinational, phase III ENVISION trial. In the EU, givosiran received a positive opinion in January 2020 for the treatment of AHP in adults and adolescents aged 12 years and older. This article summarizes the milestones in the development of givosiran leading to this first approval for the treatment of adults with AHP.

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References

  1. Fontanellas A, Ávila MA, Anderson KE, et al. Current and innovative emerging therapies for porphyrias with hepatic involvement. J Hepatol. 2019;17:422–33.

    Article  Google Scholar 

  2. Bissel DM, Anderson KE, Bonkovsky HL. Porphyria. New Engl J Med. 2017;377(9):862–72.

    Article  Google Scholar 

  3. Schmitt C, Lenglet H, Yu A, et al. Recurrrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver. J Intern Med. 2018;284(1):78–91.

    Article  CAS  Google Scholar 

  4. Elder G, Harper P, Badminton M, et al. The incidence of inherited porphyrias in Europe. J Inherit Metab Dis. 2013;36(5):849–57.

    Article  Google Scholar 

  5. Gouya L, Ventura P, Balwani M, et al. EXPLORE: a prospective, multinational, natural history study of patients with acute hepatic porphyria with recurrent attacks. Hepatology. 2019. https://doi.org/10.1002/hep.30936.

    Article  PubMed  Google Scholar 

  6. Wang B, Rudnick S, Cengia B, et al. Acute hepatic porphyrias: review and recent progress. Hepatol Commun. 2019;3(2):193–206.

    Article  CAS  Google Scholar 

  7. FDA. FDA approves first treatment for inherited rare disease [media release]. 20 Nov 2019. http://www.fda.gov/. Accessed 2 Dec 2019.

  8. Alnylam Pharmaceuticals. Givlaari (Givosiran): US prescribing information. 2019. http://www.accessdata.fda.gov/. Accessed 2 Dec 2019.

  9. European Medicines Agency. Public summary of opinion on orphan designation: synthetic double-stranded siRNA oligonucleotide directed against delta-aminolevulinic acid synthase 1 mRNA, covalently linked to a ligand containing three N-acetylgalactosamine residues for the treatment of acute hepatic porphyria [media release]. 5 Sep 2016. https://www.ema.europa.eu/. Accessed 10 Jan 2020

  10. European Medicine Agency. First treatment for acute hepatic porphyria. 31 Jan 2020. http://www.ema.europa.eu/. Accessed 3 Feb 2020.

  11. Alnylam Pharmaceuticals. Alnylam presents new positive clinical results for givosiran, an investigational RNAi therapeutic for the treatment of acute hepatic porphyrias [media release]. 12 Apr 2018. http://www.alnylam.com. Accessed 10 Jan 2020.

  12. Alnylam Pharmaceuticals. Alnylam Pharmaceuticals and Medison Pharma partner to commercialize RNAi therapeutics in Israel [media release]. 21 Jan 2019. http://www.investors.alnylam.com. Accessed 10 Jan 2020.

  13. Alnylam Pharmaceuticals. Form 8-K: entry into definitive agreement. 2005. http://www.sec.gov/Archives/edgar/data/1178670/000095013505003341/b55263ape8vk.htm. Accessed 28 Jan 2020.

  14. Chan A, Liebow A, Yasuda M, et al. Preclinical development of a subcutaneous ALAS1 RNAi therapeutic for treatment of hepatic porphyrias using circulating RNA quantification. Mol Ther Nucleic Acids. 2015;4:e263.

    Article  CAS  Google Scholar 

  15. Sardh E, Harper P, Balwani M, et al. Phase 1 trial of an RNA interference therapy for acute intermittent porphyria. N Engl J Med. 2019;380(6):549–58.

    Article  Google Scholar 

  16. Bissell DM, Gouya L, Balwani M, et al. ENVISION, a phase 3 study of safety and efficacy of givosiran, an investigational RNAi therapeutic, in acute hepatic porphyria patients [abstract no. 152 plus oral presentation]. Hepatology. 2019;70(Suppl 1):100A–1A.

    Google Scholar 

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  1. Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    Lesley J. Scott

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  1. Lesley J. Scott
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Correspondence to Lesley J. Scott.

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Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Lesley Scott is a salaried employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no relevant conflicts of interest.

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for this AdisInsight Report can be found at https://doi.org/10.6084/m9.figshare.11741715.

This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

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Scott, L.J. Givosiran: First Approval. Drugs 80, 335–339 (2020). https://doi.org/10.1007/s40265-020-01269-0

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  • DOI: https://doi.org/10.1007/s40265-020-01269-0

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