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Atlas/Gene therapy/Waskyra/Safety margin

Waskyra: what safety margin did regulators accept?

etuvetidigene autotemcel · WAS (LVV, ex vivo HSC)
Check my plan vs. these
Safety margin at NOAEL
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
NOAEL / key findings
No NOAEL; no increased mortality, tumorigenicity or toxicity related to transduced HSPCs; lymphomas were of host origin
“results do not reveal any increased mortality, tumorigenicity, or other forms of toxicity related to the transduction of mouse SV129 WKO Lin- HSPCs with w1.6W LVV.”
✓ VerifiedEMA assessment report, p. 35Source ↗

Same question, other gene therapies

Adstiladrin

nadofaragene firadenovec · IFN-alpha2b (adenovirus, intravesical)
Monkey-to-human local exposure multiple (dose-based) 3.11x for nadofaragene firadenovec, 1.87x for Syn3

Beqvez

fidanacogene elaparvovec · Factor IX
NHP: no adverse findings at doses 2- to 10-fold the recommended clinical dose

Casgevy

exagamglogene autotemcel · BCL11A enhancer (CRISPR-Cas9, ex vivo HSC)
NSG mouse toxicity dose gave only a 1.6-fold margin over the maximum human cell dose

Glybera

alipogene tiparvovec · LPL (AAV1)
No margin: dose-related muscle toxicity at the recommended clinical dose (mouse)

Hemgenix

etranacogene dezaparvovec · Factor IX
NHP no-adverse-effect dose (9x1013 gc/kg) is 4.5-fold the recommended human dose

Imlygic

talimogene laherparepvec · GM-CSF (oncolytic HSV-1)
Mouse repeat-dose SC NOAEL ~70x the recommended maximum dose (PFU/kg basis)

Itvisma

onasemnogene abeparvovec (intrathecal) · SMN1 (AAV9, intrathecal)
No margin: NHP neural toxicity findings precluded determination of a NOAEL

Kebilidi

eladocagene exuparvovec · AADC
Rat highest dose (NOAEL) gives a safety margin of 21 over the clinical dose, scaled by brain weight

Luxturna

voretigene neparvovec · RPE65
NHP NOAEL (vg/eye) is 5-fold the proposed clinical dose

Otarmeni

lunsotogene parvec · OTOF (AAV, intracochlear)
NOAEL concentrations ~2.2x (mouse) and ~2.4x (monkey) the clinical dose concentration (vg/mL)

Papzimeos

zopapogene imadenovec · HPV6/11 antigens (gorilla adenovirus)
Mouse repeat-dose level without findings gives ~5-fold safety factor over the clinical dose

Skysona

elivaldogene autotemcel · ABCD1 (LVV, ex vivo HSC)
Maximum feasible mouse dose (cells/kg) ~10-fold the minimum recommended human dose; NOAEL not determined

Strimvelis

autologous CD34+ cells transduced with ADA (no INN) · ADA (gamma-retroviral, ex vivo HSC)
Mouse dose without test-item-related effects only about half the highest human dose (cells/kg)

Zolgensma

onasemnogene abeparvovec · SMN1
No NOAEL in mice; liver/heart lesions at 0.7- to 1.4-fold the clinical dose, mortality at 2-3 times the clinical dose

Elevidys

delandistrogene moxeparvovec · Micro-dystrophin
Not stated in public reviews

Fayuvi

rebisufligene etisparvovec · SGSH (AAV9)
Not stated in public reviews

Genglycos

pariglasgene brecaparvovec · G6PC (AAV8)
Not stated in public reviews

Kresladi

marnetegragene autotemcel · ITGB2 (LVV, ex vivo HSC)
Not stated in public reviews

Lenmeldy

atidarsagene autotemcel · ARSA (LVV, ex vivo HSC)
Not stated in public reviews

Lyfgenia

lovotibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)
Not stated in public reviews

Roctavian

valoctocogene roxaparvovec · Factor VIII
Not stated in public reviews

Tudriqev

vusolimogene oderparepvec · GALV-GP + GM-CSF (oncolytic HSV-1)
Not stated in public reviews

Vyjuvek

beremagene geperpavec · COL7A1 (HSV-1, topical)
Not stated in public reviews

Zevaskyn

prademagene zamikeracel · COL7A1 (RV-modified keratinocyte sheets)
Not stated in public reviews

Zynteglo

betibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)
Not stated in public reviews

Summary across all 26 gene therapies →