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Atlas/Gene therapy/Roctavian/Skipped studies

Roctavian: genotox, carcinogenicity and repro: done or skipped?

valoctocogene roxaparvovec · Factor VIII
Check my plan vs. these
Genotoxicity
Not conducted (literature on AAV); NHP liver integration site analysis: 1.55x10^-3 IS/cell, no clonal expansion
“In terms of genotoxicity, no studies were performed with BMN 270.”
✓ VerifiedEMA assessment report, p. 34Source ↗
Carcinogenicity
Not conducted (product characteristics, tox results, population)
“As regards carcinogenicity: no carcinogenicity studies were performed with BMN 270.”
✓ VerifiedEMA assessment report, p. 35Source ↗
Reproductive & developmental
Not conducted (DART); male mouse germline transmission/mating studies showed no F1 transmission or fertility effects
“There were no ROCTAVIAN-related adverse changes on mating rates, maternal behavior, and fertility indices.”
✓ VerifiedFDA summary basis for approval, p. 12Source ↗
Safety pharmacology
Not conducted; no CNS/respiratory/CV/renal findings in toxicity studies
“Safety pharmacology studies were not performed because BMN 270 components (capsid, vector DNA, corresponding RNA and hFVIII-SQ protein) are not expected to impact major organ systems’ (central nervous system, cardiovascular, renal or respiratory) function.”
✓ VerifiedEMA assessment report, p. 24Source ↗

Same question, other gene therapies

Adstiladrin

nadofaragene firadenovec · IFN-alpha2b (adenovirus, intravesical)
Not conducted for rAd-IFN; conducted for excipient Syn3 only (Ames and chromosome aberration, negative)

Beqvez

fidanacogene elaparvovec · Factor IX
Not conducted (classical); vector integration site analysis in dog and NHP liver instead

Casgevy

exagamglogene autotemcel · BCL11A enhancer (CRISPR-Cas9, ex vivo HSC)
No conventional studies; specialized on-/off-target editing (GUIDE-seq, in silico, hybrid capture) and chromosomal aberration assessments

Elevidys

delandistrogene moxeparvovec · Micro-dystrophin
Not conducted (low-frequency random AAV integration per literature)

Fayuvi

rebisufligene etisparvovec · SGSH (AAV9)
Not conducted; weight-of-evidence risk assessment used

Genglycos

pariglasgene brecaparvovec · G6PC (AAV8)
Not conducted (low AAV integration risk); vector integration assessed in germline transmission study

Glybera

alipogene tiparvovec · LPL (AAV1)
Not conducted (standard tests not relevant); integration studies (LAM-PCR, nrLAM-PCR) instead

Hemgenix

etranacogene dezaparvovec · Factor IX
Not conducted as standard battery; integration site analysis (LAM-PCR) in mouse and NHP liver showed low random integration

Imlygic

talimogene laherparepvec · GM-CSF (oncolytic HSV-1)
Not conducted (ICH S6(R1))

Itvisma

onasemnogene abeparvovec (intrathecal) · SMN1 (AAV9, intrathecal)
Not conducted (single administration, known product characteristics, class safety profile)

Kebilidi

eladocagene exuparvovec · AADC
Not conducted (agreed with CHMP; low integration risk in post-mitotic neurons)

Kresladi

marnetegragene autotemcel · ITGB2 (LVV, ex vivo HSC)
Integration site analyses only (mouse and human transduced cells); no standard genotoxicity battery

Lenmeldy

atidarsagene autotemcel · ARSA (LVV, ex vivo HSC)
Conducted: integration site analysis, in vitro immortalization assay, tumor-prone Cdkn2a-/- mouse; no insertional transformation

Luxturna

voretigene neparvovec · RPE65
Not conducted (AAV low integration frequency; limited systemic exposure)

Lyfgenia

lovotibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)
Insertional mutagenesis assessed: in vitro immortalization (IVIM) assay and integration site analyses; low risk

Otarmeni

lunsotogene parvec · OTOF (AAV, intracochlear)
Not conducted (low AAV insertional mutagenesis risk; limited distribution beyond inner ear)

Papzimeos

zopapogene imadenovec · HPV6/11 antigens (gorilla adenovirus)
Not conducted (non-integrating, replication-incompetent adenovector; no insertional mutagenesis)

Skysona

elivaldogene autotemcel · ABCD1 (LVV, ex vivo HSC)
Standard genotox not relevant; insertional mutagenesis assessed by in vitro immortalization assay and integration site analysis

Strimvelis

autologous CD34+ cells transduced with ADA (no INN) · ADA (gamma-retroviral, ex vivo HSC)
Not conducted (conventional assays cannot detect insertional events)

Tudriqev

vusolimogene oderparepvec · GALV-GP + GM-CSF (oncolytic HSV-1)
Not conducted (not warranted based on product characteristics and safety profile)

Vyjuvek

beremagene geperpavec · COL7A1 (HSV-1, topical)
Not conducted (HSV-1 does not integrate; negligible insertional mutagenesis)

Waskyra

etuvetidigene autotemcel · WAS (LVV, ex vivo HSC)
Conventional mutagenicity not conducted; IVIM assay, vector insertion site analysis and VITA performed, no genotoxic potential

Zevaskyn

prademagene zamikeracel · COL7A1 (RV-modified keratinocyte sheets)
Not conducted (integration site analysis in transduced RDEB keratinocytes instead; no clonality or oncogene preference)

Zolgensma

onasemnogene abeparvovec · SMN1
Not conducted (low random rAAV integration per literature)

Zynteglo

betibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)
Insertional mutagenesis assessed instead of standard genotox: in vitro immortalization assay (low potential) and integration site analysis (no clonal dominance)

Summary across all 26 gene therapies →