Biology:Voretigene neparvovec
| Gene therapy | |
|---|---|
| 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 |
|
| 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
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
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
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 on 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
- ↑ 1.0 1.1 "Luxturna Australian Prescription Medicine Decision Summary". 13 August 2020. https://www.tga.gov.au/apm-summary/luxturna.
- ↑ "Luxturna Product information". 25 April 2012. https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=99512.
- ↑ "Summary Basis of Decision (SBD) for Luxturna". 23 October 2014. https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00530&lang=en.
- ↑ 4.0 4.1 "Luxturna- voretigene neparvovec-rzyl kit". 4 December 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08313a24-e7ce-457a-bb3f-161bc45517ee.
- ↑ 5.0 5.1 "Luxturna". 19 December 2017. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/luxturna.
- ↑ 6.0 6.1 "Luxturna EPAR". 24 September 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/luxturna. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ↑ 7.0 7.1 "Press Release - Investors & Media - Spark Therapeutics". http://ir.sparktx.com/phoenix.zhtml?c=253900&p=irol-newsArticle&ID=2286691.[yes|permanent dead link|dead link}}]
- ↑ "FDA approves first gene therapy for an inherited disease". Washington Post. 19 December 2017. https://www.washingtonpost.com/news/to-your-health/wp/2017/12/18/fda-approves-first-gene-therapy-for-an-inherited-disease-childhood-blindness/.
- ↑ 9.0 9.1 "FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss". 24 March 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-gene-therapy-treat-patients-rare-form-inherited-vision-loss.
- ↑ "Luxturna". 13 August 2020. https://www.tga.gov.au/apm-summary/luxturna.
- ↑ "'I never saw stars before': Gene therapy brings back 8-year-old Canadian boy's sight". 14 October 2020. https://www.ctvnews.ca/health/i-never-saw-stars-before-gene-therapy-brings-back-8-year-old-canadian-boy-s-sight-1.5145830.
- ↑ 12.0 12.1 "First Gene Therapy For Inherited Disease Gets FDA Approval". 19 December 2017. https://www.npr.org/sections/health-shots/2017/12/19/571962226/first-gene-therapy-for-inherited-disease-gets-fda-approval.
- ↑ "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. August 2017. doi:10.1016/S0140-6736(17)31868-8. PMID 28712537.
- ↑ "Spark's gene therapy for blindness is racing to a historic date with the FDA". 9 October 2017. https://www.statnews.com/2017/10/09/spark-gene-therapy/.
- ↑ "Gene Therapy for Blindness Appears Initially Effective, Says U.S. FDA". Scientific American. https://www.scientificamerican.com/article/gene-therapy-for-blindness-appears-initially-effective-says-u-s-fda/.
- ↑ "FDA approves Spark's gene therapy for rare blindness pioneered at CHOP". Philly. http://www.philly.com/philly/business/fda-approves-sparks-gene-therapy-rare-blindness-chop-20171219.html.
- ↑ "Voretigene neparvovec - Spark Therapeutics - AdisInsight". http://adisinsight.springer.com/drugs/800039212.
- ↑ "FDA Panel Backs Gene Therapy for Inherited Blindness". Medscape. 13 October 2017. https://www.medscape.com/viewarticle/887022.
- ↑ "Gene therapy for RPE65-mediated inherited retinal dystrophy completes phase 3". Lancet 390 (10097): 823–824. August 2017. doi:10.1016/S0140-6736(17)31622-7. PMID 28712536.
- ↑ "Landmark Therapy to Treat Blindness Gets One Step Closer to FDA Approval". Bloomberg.com. 12 October 2017. https://www.bloomberg.com/news/articles/2017-10-12/spark-s-gene-therapy-to-treat-blindness-gets-closer-to-approval.
- ↑ "Spark grabs FDA nod for Luxturna, a breakthrough gene therapy likely bearing a pioneering price". 19 December 2017. https://www.fiercepharma.com/regulatory/spark-therapeutics-grabs-fda-ok-for-gene-therapy-luxturna-but-isn-t-disclosing-price.
- ↑ "The anxious launch of Luxturna, a gene therapy with a record sticker price". STAT. 21 March 2018. https://www.statnews.com/2018/03/21/gene-therapy-luxturna-launch/.
- ↑ "A US drugmaker offers to cure rare blindness for $850,000". CNBC. 3 January 2018. https://www.cnbc.com/2018/01/03/spark-therapeutics-luxturna-gene-therapy-will-cost-about-850000.html.
Further reading
- "FDA advisers back gene therapy for rare form of blindness". Nature 550 (7676): 314. October 2017. doi:10.1038/nature.2017.22819. PMID 29052639. Bibcode: 2017Natur.550..314L.
- "Interview with Jean Bennett, MD, PhD". Human Gene Therapy. Clinical Development 29 (1): 7–9. March 2018. doi:10.1089/humc.2018.29032.int. PMID 29641279.
- "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. March 2018. doi:10.1016/j.joco.2018.01.006. PMID 29564403.
- "Voretigene neparvovec-rzyl for the treatment of biallelic RPE65 mutation–associated retinal dystrophy". Expert Opinion on Orphan Drugs 6 (8): 457–464. 2018. doi:10.1080/21678707.2018.1508340.
- "Emerging Gene Therapy Treatments for Inherited Retinal Diseases". Ophthalmic Surgery, Lasers & Imaging Retina 49 (7): 472–478. July 2018. doi:10.3928/23258160-20180628-02. PMID 30021033.
- "Drug and Device News". P & T 43 (2): 74–104. February 2018. PMID 29386862.
External links
- "Voretigene neparvovec". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/voretigene%20neparvovec.
 |  |
