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| pregnancy_category =
| pregnancy_category =
| routes_of_administration = [[Intravenous]]
| routes_of_administration = [[Intravenous]]
| class =
| class = [[Antihemorrhagics]]
| ATCvet =
| ATCvet =
| ATC_prefix = None <!-- scheduled to be B02BD15 in 2024 -->
| ATC_prefix = None <!-- scheduled to be B02BD15 in 2024 -->
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| legal_US_comment =
| legal_US_comment =
| legal_EU = Rx-only
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Roctavian auth">{{cite web | title=Roctavian | website=Union Register of medicinal products | date=25 August 2022 | url=https://ec.europa.eu/health/documents/community-register/html/h1668.htm | access-date=6 September 2022}}</ref>
| legal_EU_comment = <ref name="Roctavian EPAR" /><ref name="Roctavian auth">{{cite web | title=Roctavian Product information | website=Union Register of medicinal products | date=25 August 2022 | url=https://ec.europa.eu/health/documents/community-register/html/h1668.htm | access-date=6 September 2022}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_UN_comment =
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| PubChem =
| PubChem =
| IUPHAR_ligand =
| IUPHAR_ligand =
| DrugBank =
| DrugBank = DB15561
| ChemSpiderID =
| ChemSpiderID =
| UNII = 681K1JDI8M
| UNII = 681K1JDI8M
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}}
}}


'''Valoctocogene roxaparvovec''', sold under the brand name '''Roctavian''', is a [[gene therapy]] for the treatment of [[Haemophilia A|hemophilia A]].<ref name="Roctavian: Pending EC decision" /> It was developed by [[BioMarin Pharmaceutical]].<ref name="Roctavian auth" /><ref name="Roctavian: Pending EC decision" /><ref>{{Cite web| title=Roctavian (formerly Valrox/BMN 270)| url=https://hemophilianewstoday.com/bmn-270/| access-date=2021-07-01| publisher=BioNews Services, LLC| archive-date=9 July 2021| archive-url=https://web.archive.org/web/20210709183403/https://hemophilianewstoday.com/bmn-270/| url-status=live}}</ref>
'''Valoctocogene roxaparvovec''', sold under the brand name '''Roctavian''', is a [[gene therapy]] for the treatment of [[Haemophilia A|hemophilia A]].<ref name="Roctavian EPAR" /> It was developed by [[BioMarin Pharmaceutical]].<ref name="Roctavian auth" /><ref name="Roctavian: Pending EC decision" /><ref>{{Cite web| title=Roctavian (formerly Valrox/BMN 270)| url=https://hemophilianewstoday.com/bmn-270/| access-date=2021-07-01| publisher=BioNews Services, LLC| archive-date=9 July 2021| archive-url=https://web.archive.org/web/20210709183403/https://hemophilianewstoday.com/bmn-270/| url-status=live}}</ref> Valoctocogene roxaparvovec is made of a virus (AAV5) that has been modified to contain the gene for factor VIII, which is lacking in patients with haemophilia A.<ref name="Roctavian EPAR" /> It is given by [[intravenous infusion]].<ref name="Roctavian EPAR" />


The most common side effects include increased levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase (signs of possible liver problems), increased levels of the enzyme lactate dehydrogenase (sign of possible tissue damage), nausea (feeling sick) and headache.<ref name="Roctavian EPAR" />
⚫
Valoctocogene roxaparvovec was approved for medical use in the European Union in August 2022.<ref name="Roctavian auth" />


⚫
Valoctocogene roxaparvovec was approved for medical use in the European Union in August 2022.<ref name="Roctavian EPAR" /><ref name="Roctavian auth" />
⚫
== Mechanism of action ==
[[Hemophilia A]] is a bleeding disorder that results from mutations in the ''F8'' gene, which codes for the [[Factor VIII]] protein essential to the clotting process. Patients with [[hemophilia A]] produce too little [[Factor VIII]] or an ineffective version of the protein. Conventional treatment for severe cases is typically through regular intravenous infusions of [[Factor VIII (medication)|recombinant or plasma concentrated Factor VIII]].


== Medical uses ==
⚫
Valoctocogene roxaparvovec is a [[gene therapy]] that uses an [[Adeno-associated virus|adeno-associated virus 5]] (AAV5) that codes for [[Factor VIII|human Factor VIII]], together with a human liver-specific [[Promoter (genetics)|promoter]] that encourages translation in hepatocytes, not liver endothelial and sinusoidal cells, where Factor VIII is ordinarily synthesised.<ref>{{cite journal | vauthors = Bunting S, Zhang L, Xie L, Bullens S, Mahimkar R, Fong S, Sandza K, Harmon D, Yates B, Handyside B, Sihn CR, Galicia N, Tsuruda L, O'Neill CA, Bagri A, Colosi P, Long S, Vehar G, Carter B | display-authors = 6 | title = Gene Therapy with BMN 270 Results in Therapeutic Levels of FVIII in Mice and Primates and Normalization of Bleeding in Hemophilic Mice | journal = Molecular Therapy | volume = 26 | issue = 2 | pages = 496–509 | date = February 2018 | pmid = 29292164 | pmc = 5835117 | doi = 10.1016/j.ymthe.2017.12.009 }}</ref><ref>{{cite journal | vauthors = Rosen S, Tiefenbacher S, Robinson M, Huang M, Srimani J, Mackenzie D, Christianson T, Pasi KJ, Rangarajan S, Symington E, Giermasz A, Pierce GF, Kim B, Zoog SJ, Vettermann C | display-authors = 6 | title = Activity of transgene-produced B-domain-deleted factor VIII in human plasma following AAV5 gene therapy | journal = Blood | volume = 136 | issue = 22 | pages = 2524–2534 | date = November 2020 | pmid = 32915950 | pmc = 7714098 | doi = 10.1182/blood.2020005683 }}</ref> By [[Transfection|transfecting]] a functional version of the ''F8'' gene into liver cells, the patient would be able to produce sufficient amounts biologically.
Valoctocogene roxaparvovec is [[indicated]] for the treatment of severe haemophilia A (congenital factor VIII deficiency) in adults without a history of factor VIII inhibitors and without detectable antibodies to adeno-associated virus serotype 5 (AAV5).<ref name="Roctavian EPAR" />

⚫
== Mechanism of action ==
⚫
Valoctocogene roxaparvovec is a [[gene therapy]] that uses an [[Adeno-associated virus|adeno-associated virus 5]] (AAV5) that codes for [[Factor VIII|human Factor VIII]], together with a human liver-specific [[Promoter (genetics)|promoter]] that encourages translation in hepatocytes, not liver endothelial and sinusoidal cells, where Factor VIII is ordinarily synthesised.<ref>{{cite journal | vauthors = Bunting S, Zhang L, Xie L, Bullens S, Mahimkar R, Fong S, Sandza K, Harmon D, Yates B, Handyside B, Sihn CR, Galicia N, Tsuruda L, O'Neill CA, Bagri A, Colosi P, Long S, Vehar G, Carter B | display-authors = 6 | title = Gene Therapy with BMN 270 Results in Therapeutic Levels of FVIII in Mice and Primates and Normalization of Bleeding in Hemophilic Mice | journal = Molecular Therapy | volume = 26 | issue = 2 | pages = 496–509 | date = February 2018 | pmid = 29292164 | pmc = 5835117 | doi = 10.1016/j.ymthe.2017.12.009 }}</ref><ref>{{cite journal | vauthors = Rosen S, Tiefenbacher S, Robinson M, Huang M, Srimani J, Mackenzie D, Christianson T, Pasi KJ, Rangarajan S, Symington E, Giermasz A, Pierce GF, Kim B, Zoog SJ, Vettermann C | display-authors = 6 | title = Activity of transgene-produced B-domain-deleted factor VIII in human plasma following AAV5 gene therapy | journal = Blood | volume = 136 | issue = 22 | pages = 2524–2534 | date = November 2020 | pmid = 32915950 | pmc = 7714098 | doi = 10.1182/blood.2020005683 }}</ref>


== History ==
== History ==
The [[Food and Drug Administration]] granted valoctocogene roxaparvovec [[orphan drug]] status in 2016<ref>{{Cite web|last=BioMarin Pharmaceutical Inc.|date=2016-03-01|title=BioMarin Receives Orphan Drug Designation From FDA for First AAV-Factor VIII Gene Therapy, BMN 270, for Patients With Hemophilia A|url=https://www.globenewswire.com/news-release/2016/03/01/816024/18475/en/BioMarin-Receives-Orphan-Drug-Designation-From-FDA-for-First-AAV-Factor-VIII-Gene-Therapy-BMN-270-for-Patients-With-Hemophilia-A.html|url-status=live|access-date=2021-07-01|website=GlobeNewswire News Room|archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709184317/https://www.globenewswire.com/news-release/2016/03/01/816024/18475/en/BioMarin-Receives-Orphan-Drug-Designation-From-FDA-for-First-AAV-Factor-VIII-Gene-Therapy-BMN-270-for-Patients-With-Hemophilia-A.html}}</ref> and [[breakthrough therapy]] designation in 2017.<ref>{{Cite web|title=FDA Grants Breakthrough Therapy Designation for BioMarin's Valoctocogene Roxaparvovec (formerly BMN 270), an Investigational Gene Therapy for Hemophilia A|url=https://investors.biomarin.com/2017-10-26-FDA-Grants-Breakthrough-Therapy-Designation-for-BioMarins-Valoctocogene-Roxaparvovec-formerly-BMN-270-an-Investigational-Gene-Therapy-for-Hemophilia-A|access-date=2021-07-01|website=BioMarin Investors|archive-date=23 June 2021|archive-url=https://web.archive.org/web/20210623230220/https://investors.biomarin.com/2017-10-26-FDA-Grants-Breakthrough-Therapy-Designation-for-BioMarins-Valoctocogene-Roxaparvovec-formerly-BMN-270-an-Investigational-Gene-Therapy-for-Hemophilia-A|url-status=live}}</ref>
The US [[Food and Drug Administration]] granted valoctocogene roxaparvovec [[orphan drug]] status in 2016,<ref>{{Cite press release |date=2016-03-01|title=BioMarin Receives Orphan Drug Designation From FDA for First AAV-Factor VIII Gene Therapy, BMN 270, for Patients With Hemophilia A|url=https://www.globenewswire.com/news-release/2016/03/01/816024/18475/en/BioMarin-Receives-Orphan-Drug-Designation-From-FDA-for-First-AAV-Factor-VIII-Gene-Therapy-BMN-270-for-Patients-With-Hemophilia-A.html|url-status=live|access-date=2021-07-01 |publisher=BioMarin Pharmaceutical Inc. |via=GlobeNewswire |archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709184317/https://www.globenewswire.com/news-release/2016/03/01/816024/18475/en/BioMarin-Receives-Orphan-Drug-Designation-From-FDA-for-First-AAV-Factor-VIII-Gene-Therapy-BMN-270-for-Patients-With-Hemophilia-A.html}}</ref> and [[breakthrough therapy]] designation in 2017.<ref>{{Cite press release |title=FDA Grants Breakthrough Therapy Designation for BioMarin's Valoctocogene Roxaparvovec (formerly BMN 270), an Investigational Gene Therapy for Hemophilia A|url=https://investors.biomarin.com/2017-10-26-FDA-Grants-Breakthrough-Therapy-Designation-for-BioMarins-Valoctocogene-Roxaparvovec-formerly-BMN-270-an-Investigational-Gene-Therapy-for-Hemophilia-A|access-date=2021-07-01|website=BioMarin Investors|archive-date=23 June 2021|archive-url=https://web.archive.org/web/20210623230220/https://investors.biomarin.com/2017-10-26-FDA-Grants-Breakthrough-Therapy-Designation-for-BioMarins-Valoctocogene-Roxaparvovec-formerly-BMN-270-an-Investigational-Gene-Therapy-for-Hemophilia-A|url-status=live}}</ref>


However, in late August 2020, BioMarin received a [[Complete Response Letter]] from the FDA, indicating that its [[Biologics license application|Biologics License Application]] (which would have made valoctocogene roxaparvovec the first gene therapy to be approved for a [[Coagulopathy|bleeding disorder]]) would not be approved.<ref>{{Cite web|title=BioMarin Receives Complete Response Letter (CRL) from FDA for Valoctocogene Roxaparvovec Gene Therapy for Severe Hemophilia A|url=https://www.biospace.com/article/biomarin-receives-complete-response-letter-crl-from-fda-for-valoctocogene-roxaparvovec-gene-therapy-for-severe-hemophilia-a/|access-date=2021-07-01|website=BioSpace|archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709184219/https://www.biospace.com/article/biomarin-receives-complete-response-letter-crl-from-fda-for-valoctocogene-roxaparvovec-gene-therapy-for-severe-hemophilia-a/|url-status=live}}</ref> The regulator was concerned that differences between results from the [[Phases of clinical research|phase I/II trials]] (the 270-201 study)<ref>{{Cite journal|last=BioMarin Pharmaceutical|date=2021-01-20|title=A Phase 1/2, Dose-Escalation, Safety, Tolerability and Efficacy Study of Valoctocogene Roxaparvovec, an Adenovirus-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Patients With Severe Haemophilia A|url=https://clinicaltrials.gov/ct2/show/NCT02576795|journal=|access-date=1 July 2021|archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709182333/https://clinicaltrials.gov/ct2/show/NCT02576795|url-status=live}}</ref> and the [[Phases of clinical research|phase III trial]] (the 270-301 study)<ref>{{Cite journal|last=BioMarin Pharmaceutical|date=2021-01-15|title=A Phase 3 Open-Label, Single-Arm Study To Evaluate The Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL Receiving Prophylactic FVIII Infusions|url=https://clinicaltrials.gov/ct2/show/NCT03370913|journal=|access-date=1 July 2021|archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709181535/https://clinicaltrials.gov/ct2/show/NCT03370913|url-status=live}}</ref> were too dissimilar with regard to durability, the latter suggesting that the protective effect of valoctocogene roxaparvovec wore off after approx. 12-18 months.<ref name=":0">{{Cite web|vauthors=Adams B|title=FDA gets out its red pen again, rejecting BioMarin's gene therapy valrox amid durability worries|url=https://www.fiercebiotech.com/biotech/fda-gets-out-its-red-pen-again-rejecting-biomarin-s-gene-therapy-valrox-amid-durability|url-status=live|access-date=2021-07-01|website=FierceBiotech|date=19 August 2020 |archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709182220/https://www.fiercebiotech.com/biotech/fda-gets-out-its-red-pen-again-rejecting-biomarin-s-gene-therapy-valrox-amid-durability}}</ref> The FDA advised BioMarin to resubmit two-year follow-up evidence of safety and effectiveness on all study participants, which puts the earliest date of resubmission to late 2021.<ref name=":0" />
However, in late August 2020, BioMarin received a [[Complete Response Letter]] from the FDA, indicating that its [[Biologics license application|Biologics License Application]] (which would have made valoctocogene roxaparvovec the first gene therapy to be approved for a [[Coagulopathy|bleeding disorder]]) would not be approved.<ref>{{Cite web|title=BioMarin Receives Complete Response Letter (CRL) from FDA for Valoctocogene Roxaparvovec Gene Therapy for Severe Hemophilia A|url=https://www.biospace.com/article/biomarin-receives-complete-response-letter-crl-from-fda-for-valoctocogene-roxaparvovec-gene-therapy-for-severe-hemophilia-a/|access-date=2021-07-01|website=BioSpace|archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709184219/https://www.biospace.com/article/biomarin-receives-complete-response-letter-crl-from-fda-for-valoctocogene-roxaparvovec-gene-therapy-for-severe-hemophilia-a/|url-status=live}}</ref> The regulator was concerned that differences between results from the [[Phases of clinical research|phase I/II trials]] (the 270-201 study)<ref>{{Cite journal|last=BioMarin Pharmaceutical|date=2021-01-20|title=Gene Therapy Study in Severe Haemophilia A Patients (270-201) |url=https://clinicaltrials.gov/ct2/show/NCT02576795|journal=ClinicalTrials.gov|access-date=1 July 2021|archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709182333/https://clinicaltrials.gov/ct2/show/NCT02576795|url-status=live}}</ref> and the [[Phases of clinical research|phase III trial]] (the 270-301 study)<ref>{{Cite journal|last=BioMarin Pharmaceutical|date=2021-01-15|title=A Phase 3 Open-Label, Single-Arm Study To Evaluate The Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL Receiving Prophylactic FVIII Infusions|url=https://clinicaltrials.gov/ct2/show/NCT03370913|journal=|access-date=1 July 2021|archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709181535/https://clinicaltrials.gov/ct2/show/NCT03370913|url-status=live}}</ref> were too dissimilar with regard to durability, the latter suggesting that the protective effect of valoctocogene roxaparvovec wore off after approx. 12-18 months.<ref name=":0">{{Cite web|vauthors=Adams B|title=FDA gets out its red pen again, rejecting BioMarin's gene therapy valrox amid durability worries|url=https://www.fiercebiotech.com/biotech/fda-gets-out-its-red-pen-again-rejecting-biomarin-s-gene-therapy-valrox-amid-durability|url-status=live|access-date=2021-07-01|website=FierceBiotech|date=19 August 2020 |archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709182220/https://www.fiercebiotech.com/biotech/fda-gets-out-its-red-pen-again-rejecting-biomarin-s-gene-therapy-valrox-amid-durability}}</ref>


== Society and culture ==
== Society and culture ==
=== Legal status ===
=== Legal status ===
On 23 June 2022, the [[Committee for Medicinal Products for Human Use]] (CHMP) of the [[European Medicines Agency]] (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Roctavian, intended for the treatment of severe haemophilia A.<ref>{{cite press release | title=First gene therapy to treat severe haemophilia A | website=[[European Medicines Agency]] (EMA) | date=24 June 2022 | url=https://www.ema.europa.eu/en/news/first-gene-therapy-treat-severe-haemophilia | access-date=26 June 2022 | archive-date=26 June 2022 | archive-url=https://web.archive.org/web/20220626014840/https://www.ema.europa.eu/en/news/first-gene-therapy-treat-severe-haemophilia | url-status=live }}</ref><ref name="Roctavian: Pending EC decision" /> As Roctavian is an advanced therapy medicinal product, the CHMP positive opinion is based on an assessment by the Committee for Advanced Therapies.<ref name="Roctavian: Pending EC decision" /> The applicant for this medicinal product is BioMarin International Limited.<ref name="Roctavian: Pending EC decision">{{cite web | title=Roctavian: Pending EC decision | website=[[European Medicines Agency]] (EMA) | date=23 June 2022 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/roctavian | access-date=26 June 2022 | archive-date=26 June 2022 | archive-url=https://web.archive.org/web/20220626014831/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/roctavian | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Valoctocogene roxaparvovec was approved for medical use in the European Union in August 2022.<ref name="Roctavian auth" />
On 23 June 2022, the [[Committee for Medicinal Products for Human Use]] (CHMP) of the [[European Medicines Agency]] (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Roctavian, intended for the treatment of severe haemophilia A.<ref>{{cite press release | title=First gene therapy to treat severe haemophilia A | website=[[European Medicines Agency]] (EMA) | date=24 June 2022 | url=https://www.ema.europa.eu/en/news/first-gene-therapy-treat-severe-haemophilia | access-date=26 June 2022 | archive-date=26 June 2022 | archive-url=https://web.archive.org/web/20220626014840/https://www.ema.europa.eu/en/news/first-gene-therapy-treat-severe-haemophilia | url-status=live }}</ref><ref name="Roctavian: Pending EC decision" /> As Roctavian is an advanced therapy medicinal product, the CHMP positive opinion is based on an assessment by the Committee for Advanced Therapies.<ref name="Roctavian: Pending EC decision" /> The applicant for this medicinal product is BioMarin International Limited.<ref name="Roctavian: Pending EC decision">{{cite web | title=Roctavian: Pending EC decision | website=[[European Medicines Agency]] (EMA) | date=23 June 2022 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/roctavian | access-date=26 June 2022 | archive-date=26 June 2022 | archive-url=https://web.archive.org/web/20220626014831/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/roctavian | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Valoctocogene roxaparvovec was approved for medical use in the European Union in August 2022.<ref name="Roctavian EPAR">{{cite web | title=Roctavian EPAR | website=[[European Medicines Agency]] (EMA) | date=20 June 2022 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/roctavian-0 | access-date=4 March 2023}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref name="Roctavian auth" />


== References ==
== References ==
Line 129: Line 132:
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/valoctocogene%20roxaparvovec | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Valoctocogene roxaparvovec }}
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/valoctocogene%20roxaparvovec | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Valoctocogene roxaparvovec }}


{{Other hematological agents}}
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{{Portal bar | Medicine}}


Revision as of 05:13, 4 March 2023

Valoctocogene roxaparvovec
Gene therapy
Target geneF8
VectorAAV5
Nucleic acid typeDNA
Delivery methodIV
Clinical data
Trade namesRoctavian
Other namesBMN-270, Valrox
Routes of
administration		Intravenous
Drug classAntihemorrhagics
ATC code
  • None
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG

Valoctocogene roxaparvovec, sold under the brand name Roctavian, is a gene therapy for the treatment of hemophilia A.[1] It was developed by BioMarin Pharmaceutical.[2][3][4] Valoctocogene roxaparvovec is made of a virus (AAV5) that has been modified to contain the gene for factor VIII, which is lacking in patients with haemophilia A.[1] It is given by intravenous infusion.[1]

The most common side effects include increased levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase (signs of possible liver problems), increased levels of the enzyme lactate dehydrogenase (sign of possible tissue damage), nausea (feeling sick) and headache.[1]

Valoctocogene roxaparvovec was approved for medical use in the European Union in August 2022.[1][2]

Medical uses

Valoctocogene roxaparvovec is indicated for the treatment of severe haemophilia A (congenital factor VIII deficiency) in adults without a history of factor VIII inhibitors and without detectable antibodies to adeno-associated virus serotype 5 (AAV5).[1]

Mechanism of action

Valoctocogene roxaparvovec is a gene therapy that uses an adeno-associated virus 5 (AAV5) that codes for human Factor VIII, together with a human liver-specific promoter that encourages translation in hepatocytes, not liver endothelial and sinusoidal cells, where Factor VIII is ordinarily synthesised.[5][6]

History

The US Food and Drug Administration granted valoctocogene roxaparvovec orphan drug status in 2016,[7] and breakthrough therapy designation in 2017.[8]

However, in late August 2020, BioMarin received a Complete Response Letter from the FDA, indicating that its Biologics License Application (which would have made valoctocogene roxaparvovec the first gene therapy to be approved for a bleeding disorder) would not be approved.[9] The regulator was concerned that differences between results from the phase I/II trials (the 270-201 study)[10] and the phase III trial (the 270-301 study)[11] were too dissimilar with regard to durability, the latter suggesting that the protective effect of valoctocogene roxaparvovec wore off after approx. 12-18 months.[12]

Society and culture

Legal status

On 23 June 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Roctavian, intended for the treatment of severe haemophilia A.[13][3] As Roctavian is an advanced therapy medicinal product, the CHMP positive opinion is based on an assessment by the Committee for Advanced Therapies.[3] The applicant for this medicinal product is BioMarin International Limited.[3] Valoctocogene roxaparvovec was approved for medical use in the European Union in August 2022.[1][2]

References

  1. ^ a b c d e f g h "Roctavian EPAR". European Medicines Agency (EMA). 20 June 2022. Retrieved 4 March 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  2. ^ a b c d "Roctavian Product information". Union Register of medicinal products. 25 August 2022. Retrieved 6 September 2022.
  3. ^ a b c d "Roctavian: Pending EC decision". European Medicines Agency (EMA). 23 June 2022. Archived from the original on 26 June 2022. Retrieved 26 June 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. ^ "Roctavian (formerly Valrox/BMN 270)". BioNews Services, LLC. Archived from the original on 9 July 2021. Retrieved 1 July 2021.
  5. ^ Bunting S, Zhang L, Xie L, Bullens S, Mahimkar R, Fong S, et al. (February 2018). "Gene Therapy with BMN 270 Results in Therapeutic Levels of FVIII in Mice and Primates and Normalization of Bleeding in Hemophilic Mice". Molecular Therapy. 26 (2): 496–509. doi:10.1016/j.ymthe.2017.12.009. PMC 5835117. PMID 29292164.
  6. ^ Rosen S, Tiefenbacher S, Robinson M, Huang M, Srimani J, Mackenzie D, et al. (November 2020). "Activity of transgene-produced B-domain-deleted factor VIII in human plasma following AAV5 gene therapy". Blood. 136 (22): 2524–2534. doi:10.1182/blood.2020005683. PMC 7714098. PMID 32915950.
  7. ^ "BioMarin Receives Orphan Drug Designation From FDA for First AAV-Factor VIII Gene Therapy, BMN 270, for Patients With Hemophilia A" (Press release). BioMarin Pharmaceutical Inc. 1 March 2016. Archived from the original on 9 July 2021. Retrieved 1 July 2021 – via GlobeNewswire.
  8. ^ "FDA Grants Breakthrough Therapy Designation for BioMarin's Valoctocogene Roxaparvovec (formerly BMN 270), an Investigational Gene Therapy for Hemophilia A". BioMarin Investors (Press release). Archived from the original on 23 June 2021. Retrieved 1 July 2021.
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  12. ^ Adams B (19 August 2020). "FDA gets out its red pen again, rejecting BioMarin's gene therapy valrox amid durability worries". FierceBiotech. Archived from the original on 9 July 2021. Retrieved 1 July 2021.
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