Voretigene neparvovec
Gene therapy | |
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Target gene | RPE65 |
Vector | Adeno-associated virus serotype 2 |
Nucleic acid type | DNA |
Clinical data | |
Trade names | Luxturna |
Other names | voretigene neparvovec-rzyl |
AHFS/Drugs.com | Professional Drug Facts |
License data | |
Pregnancy category |
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Routes of administration | Subretinal injection |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
CAS Number | |
DrugBank | |
UNII | |
KEGG |
Voretigene neparvovec, sold under the brand name Luxturna, is a gene therapy medication for the treatment of Leber congenital amaurosis.[4]
Leber's congenital amaurosis, or biallelic RPE65-mediated inherited retinal disease, is an inherited disorder causing progressive blindness. Voretigene is the first treatment available for this condition.[7] The gene therapy is not a cure for the condition, but substantially improves vision in those treated.[8] It is given as a subretinal injection.
Voretigene neparvovec was approved for medical use in the United States in December 2017,[9] Australia in August 2020[10] and in Canada, in October 2020.[11] It is the first in vivo gene therapy approved by the US Food and Drug Administration (FDA).[12]
Medical uses
[edit]Voretigene neparvovec is indicated for the treatment of people with vision loss due to inherited retinal dystrophy caused by confirmed biallelic RPE65 mutations and who have sufficient viable retinal cells.[6]
Chemistry and production
[edit]Voretigene neparvovec is an AAV2 vector containing human RPE65 cDNA with a modified Kozak sequence. The virus is grown in HEK 293 cells and purified for administration.[13]
History
[edit]It was developed by Spark Therapeutics and Children's Hospital of Philadelphia.[14][15][16]
It was granted orphan drug designation for Leber congenital amaurosis and retinitis pigmentosa.[17][18] A biologics license application was submitted to the US Food and Drug Administration (FDA) in July 2017 with Priority Review.[7] Phase III clinical trial results were published in August 2017.[19] On 12 October 2017, a key advisory panel to the FDA, composed of 16 experts, unanimously recommended approval of the treatment.[20] The FDA approved the drug in December 2017.[9][5] With the approval, Spark Therapeutics received a pediatric disease priority review voucher.[21]
The first commercial sale of voretigene neparvovec, which was also the first sale of any gene therapy product in the United States, occurred in March 2018.[22][12] The price of the treatment at the time was announced as being $425,000 per eye.[23]
References
[edit]- ^ a b "Luxturna Australian Prescription Medicine Decision Summary". Therapeutic Goods Administration (TGA). 13 August 2020. Retrieved 16 August 2020.
- ^ "Luxturna Product information". Health Canada. 25 April 2012. Retrieved 21 October 2020.
- ^ "Summary Basis of Decision (SBD) for Luxturna". Health Canada. 23 October 2014. Retrieved 29 May 2022.
- ^ a b "Luxturna- voretigene neparvovec-rzyl kit". DailyMed. 4 December 2019. Retrieved 14 August 2020.
- ^ a b "Luxturna". U.S. Food and Drug Administration (FDA). 19 December 2017. Retrieved 2 April 2020.
- ^ a b "Luxturna EPAR". European Medicines Agency (EMA). 24 September 2018. Retrieved 21 October 2020.
- ^ a b "Press Release - Investors & Media - Spark Therapeutics". Ir.sparktx.com. Retrieved 9 October 2017.[permanent dead link]
- ^ McGinley L (19 December 2017). "FDA approves first gene therapy for an inherited disease". Washington Post.
- ^ a b "FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss". U.S. Food and Drug Administration (FDA). 24 March 2020. Retrieved 28 November 2022.
- ^ "Luxturna". Therapeutic Goods Administration (TGA). 13 August 2020. Retrieved 22 September 2020.
- ^ "'I never saw stars before': Gene therapy brings back 8-year-old Canadian boy's sight". CTVNews. 14 October 2020. Retrieved 21 October 2020.
- ^ a b "First Gene Therapy For Inherited Disease Gets FDA Approval". NPR. 19 December 2017.
- ^ Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, et al. (August 2017). "Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial". Lancet. 390 (10097): 849–860. doi:10.1016/S0140-6736(17)31868-8. PMC 5726391. PMID 28712537.
{{cite journal}}
: CS1 maint: overridden setting (link) - ^ "Spark's gene therapy for blindness is racing to a historic date with the FDA". Statnews.com. 9 October 2017. Retrieved 9 October 2017.
- ^ Clarke T. "Gene Therapy for Blindness Appears Initially Effective, Says U.S. FDA". Scientific American. Retrieved 12 October 2017.
- ^ "FDA approves Spark's gene therapy for rare blindness pioneered at CHOP". Philly. Retrieved 24 March 2018.
- ^ "Voretigene neparvovec - Spark Therapeutics - AdisInsight". adisinsight.springer.com.
- ^ Lewis R (13 October 2017). "FDA Panel Backs Gene Therapy for Inherited Blindness". Medscape.
- ^ Lee H, Lotery A (August 2017). "Gene therapy for RPE65-mediated inherited retinal dystrophy completes phase 3". Lancet. 390 (10097): 823–824. doi:10.1016/S0140-6736(17)31622-7. PMID 28712536. S2CID 26983863.
- ^ "Landmark Therapy to Treat Blindness Gets One Step Closer to FDA Approval". Bloomberg.com. 12 October 2017. Retrieved 12 October 2017.
- ^ "Spark grabs FDA nod for Luxturna, a breakthrough gene therapy likely bearing a pioneering price". FiercePharma. 19 December 2017.
- ^ "The anxious launch of Luxturna, a gene therapy with a record sticker price". STAT. 21 March 2018. Retrieved 24 March 2018.
- ^ Tirrell M (3 January 2018). "A US drugmaker offers to cure rare blindness for $850,000". CNBC. Retrieved 3 January 2018.
Further reading
[edit]- Ledford H (October 2017). "FDA advisers back gene therapy for rare form of blindness". Nature. 550 (7676): 314. Bibcode:2017Natur.550..314L. doi:10.1038/nature.2017.22819. PMID 29052639.
- Wilson JM (March 2018). "Interview with Jean Bennett, MD, PhD". Human Gene Therapy. Clinical Development. 29 (1): 7–9. doi:10.1089/humc.2018.29032.int. PMID 29641279.
- Ameri H (March 2018). "Prospect of retinal gene therapy following commercialization of voretigene neparvovec-rzyl for retinal dystrophy mediated by RPE65 mutation". Journal of Current Ophthalmology. 30 (1): 1–2. doi:10.1016/j.joco.2018.01.006. PMC 5859497. PMID 29564403.
- Russell S, Bennett J, Maguire AM, High KA (2018). "Voretigene neparvovec-rzyl for the treatment of biallelic RPE65 mutation–associated retinal dystrophy". Expert Opinion on Orphan Drugs. 6 (8): 457–464. doi:10.1080/21678707.2018.1508340. S2CID 81437112.
- Bakall B, Hariprasad SM, Klein KA (July 2018). "Emerging Gene Therapy Treatments for Inherited Retinal Diseases". Ophthalmic Surgery, Lasers & Imaging Retina. 49 (7): 472–478. doi:10.3928/23258160-20180628-02. PMID 30021033.
- "Drug and Device News". P & T. 43 (2): 74–104. February 2018. PMC 5768294. PMID 29386862.