Request an invite
Atlas/Gene therapy/Strimvelis/First dose

Strimvelis: how was the first human dose set?

autologous CD34+ cells transduced with ADA (no INN) · ADA (gamma-retroviral, ex vivo HSC)
Check my plan vs. these
First-in-human starting dose
No nonclinical dose justification stated; first (investigator-initiated) protocol based on nonclinically optimised transduction conditions
“The first ADA/SCID clinical protocol for Study Number AD1117054 was based on the optimised transduction conditions from the nonclinical studies described above.”
✓ VerifiedEMA assessment report, p. 21Source ↗
NOAEL / key findings
No test-item-related adverse effects at 10x10^6 CD34+ cells/kg (about half max clinical dose); busulfan-related gonadal atrophy, deaths
“In this study, mice were administered 10 x106 CD34+ cells/kg (approximately the midpoint of the dose range to be infused in human subjects) without test-item-related adverse effects.”
✓ VerifiedEMA assessment report, p. 26Source ↗

Same question, other gene therapies

Glybera

alipogene tiparvovec · LPL (AAV1)
Not explicitly justified; clinical 1x10^12 gc/kg lies within active range in LPL-/- mice (10^11-10^13); tox covered 10x

Itvisma

onasemnogene abeparvovec (intrathecal) · SMN1 (AAV9, intrathecal)
NHP-tolerated 1.2x10^13 vg/animal scaled 10-fold by CSF volume to human starting dose 1.2x10^14 vg/patient

Kebilidi

eladocagene exuparvovec · AADC
Prior adult PD rAAV2-hAADC clinical doses (up to 3x10^11 vg) scaled by brain mass; 1.8x10^11 vg (~60%)

Luxturna

voretigene neparvovec · RPE65
FIH start dose basis not stated; clinical dose chosen over broad efficacious range using safety data (NHP NOAEL 5x clinical dose)

Otarmeni

lunsotogene parvec · OTOF (AAV, intracochlear)
PD Emax modeling of mouse ABR data: plateau >2e13 vg/mL; clinical 3e13 vg/mL (1.5x), concentration-scaled NOAEL margins 2.2-2.4x

Papzimeos

zopapogene imadenovec · HPV6/11 antigens (gorilla adenovirus)
Not explicitly stated; mouse repeat-dose 1x10^10 VP gives ~5-fold safety factor over clinical 5x10^11 PU dose

Zolgensma

onasemnogene abeparvovec · SMN1
Mouse efficacy: doses doubling (7.4e13) and fully restoring (1.2e14 vg/kg) SMNdelta7 lifespan; MTD 1.5e14 set retrospectively

Adstiladrin

nadofaragene firadenovec · IFN-alpha2b (adenovirus, intravesical)
Not stated in public reviews

Beqvez

fidanacogene elaparvovec · Factor IX
Not stated in public reviews

Casgevy

exagamglogene autotemcel · BCL11A enhancer (CRISPR-Cas9, ex vivo HSC)
Not stated in public reviews

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

Hemgenix

etranacogene dezaparvovec · Factor IX
Not stated for FIH; later clinical dosing informed by predecessor AMT-060 clinical data

Imlygic

talimogene laherparepvec · GM-CSF (oncolytic HSV-1)
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

Skysona

elivaldogene autotemcel · ABCD1 (LVV, ex vivo HSC)
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

Waskyra

etuvetidigene autotemcel · WAS (LVV, ex vivo HSC)
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 →