Adstiladrin
nadofaragene firadenovec · IFN-alpha2b (adenovirus, intravesical)Cynomolgus monkey for rAd-IFN/Syn3 GLP tox; rat and monkey for excipient Syn3
Zynteglo: which tox species, and why?
betibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)
Species
Mouse only (beta-thalassaemic Hbbth1/th1 and wild-type C57BL/6; immunodeficient NSG for human HSC); murine surrogate product
“BB305 LVV-transduced cells were evaluated in the β-thalassaemic (Hbbth1/th1) mouse model and in the NSG mice.”
Why that species
Thalassaemic mouse model gives disease-relevant POC; NSG mice cannot reject human CD34+ HSCs
“they are therefore unable to reject the human CD34+ HSCs.”
Surrogate molecule
Yes: test articles were surrogates - murine BB305-transduced thalassaemic BM cells or human healthy-donor HSCs in NSG mice
“the test articles used during non-clinical studies were surrogates, and consisted of either thalassaemic mouse bone marrow cells transduced with BB305 LVV”
Species: general tox
Mouse only: β-thalassemic (primary transplant) and wild-type C57BL/6 (secondary transplant) mice given transduced murine BMCs
“In vivo pharmacology and toxicology studies were conducted to evaluate the activity and safety of BB305 LVV-transduced murine BM cells (BMCs) following primary and secondary transplantation in β-thalassemic and wild-type C57BL/6 mice, respectively.”
Species: DART
Not conducted (not warranted based on product characteristics and safety profile)
“Carcinogenicity and developmental and reproductive toxicity studies were not conducted with beti-cel. These studies are not warranted based on the product characteristics and safety profile.”
Species: carcinogenicity
Not conducted (not warranted based on product characteristics and safety profile)
“Carcinogenicity and developmental and reproductive toxicity studies were not conducted with beti-cel. These studies are not warranted based on the product characteristics and safety profile.”
Surrogate used in
Yes: BB305-transduced thalassaemic mouse BM cells in Hbbth1/th1 mice and healthy-donor human HSCs in NSG mice
“the test articles used during non-clinical studies were surrogates, and consisted of either thalassaemic mouse bone marrow cells transduced with BB305 LVV, or human healthy donor HSCs transduced with BB305 LVV, administered to β-thalassaemic (Hbbth1/th1) mice and immunodeficient NOD scid gamma (NSG) mice, respectively.”
Same question, other gene therapies
Beqvez
fidanacogene elaparvovec · Factor IXCynomolgus monkey and mouse (tox); hemophilia B dog and mouse (pharmacology); rabbit (shedding)
Casgevy
exagamglogene autotemcel · BCL11A enhancer (CRISPR-Cas9, ex vivo HSC)Mouse only (irradiated NSG immunodeficient xenotransplant mice)
Elevidys
delandistrogene moxeparvovec · Micro-dystrophinMouse only (wild-type C57BL/6J and mdx disease model); NHP only in non-GLP supporting studies
Fayuvi
rebisufligene etisparvovec · SGSH (AAV9)Wild-type C57BL/6 mice only (6-month and 3-month GLP studies)
Genglycos
pariglasgene brecaparvovec · G6PC (AAV8)Mouse (adult and juvenile C57BL/6N) and juvenile cynomolgus monkey; GLP single-dose studies
Glybera
alipogene tiparvovec · LPL (AAV1)Wild-type mouse only for GLP tox; PD in LPL-/- mice and LPL-deficient cats; biodistribution in cats, mice, rabbits
Hemgenix
etranacogene dezaparvovec · Factor IXMouse and cynomolgus monkey
Imlygic
talimogene laherparepvec · GM-CSF (oncolytic HSV-1)Mouse (BALB/c) for GLP tox; single-dose studies also in rats and dogs; no permissive/relevant species for human GM-CSF
Itvisma
onasemnogene abeparvovec (intrathecal) · SMN1 (AAV9, intrathecal)Cynomolgus monkey (pivotal IT tox); FVB mice for ICV safety and fertility/EFD; SMA piglet and SMN-delta7 mouse pharmacology
Kebilidi
eladocagene exuparvovec · AADCRat (pivotal GLP); cynomolgus monkey for biodistribution/excipient studies
Kresladi
marnetegragene autotemcel · ITGB2 (LVV, ex vivo HSC)Mouse only (CD18HYP/CD18KO disease models, recipient mice, NSG mice); no large-animal tox
Lenmeldy
atidarsagene autotemcel · ARSA (LVV, ex vivo HSC)Mouse (As2-/- MLD model, murine ARSA-LV HSPCs) for pivotal GLP; immunodeficient mice for human-cell biodistribution
Luxturna
voretigene neparvovec · RPE65Dog (normal-sighted and RPE65-mutant Briard) and non-human primate
Lyfgenia
lovotibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)Mouse only (beta-thalassemic and wild-type C57BL/6 transplant models; immunodeficient mice for human cells)
Otarmeni
lunsotogene parvec · OTOF (AAV, intracochlear)Mouse (Otof-Q828X hom disease model) and cynomolgus monkey
Papzimeos
zopapogene imadenovec · HPV6/11 antigens (gorilla adenovirus)Mouse only (wild-type C57BL/6); no NHP studies
Roctavian
valoctocogene roxaparvovec · Factor VIIIMouse (CD1, Rag2-/-, hemophilia A models) and cynomolgus/rhesus monkey; all males
Skysona
elivaldogene autotemcel · ABCD1 (LVV, ex vivo HSC)Mouse only: myeloablated immunodeficient NSG/NSGS mice given human CD34+ HSCs
Strimvelis
autologous CD34+ cells transduced with ADA (no INN) · ADA (gamma-retroviral, ex vivo HSC)NSG immunodeficient mouse only (xenograft of transduced human CD34+ cells)
Tudriqev
vusolimogene oderparepvec · GALV-GP + GM-CSF (oncolytic HSV-1)Tumor-bearing immunocompetent mice (TUDRIQEV, mRP1) and healthy rats (murine surrogate mRP1)
Vyjuvek
beremagene geperpavec · COL7A1 (HSV-1, topical)Mouse only (BALB/c) for GLP tox; single species
Waskyra
etuvetidigene autotemcel · WAS (LVV, ex vivo HSC)Mouse only: WAS knockout (C57BL/6 and SV129) mice with murine surrogate cells; Rag2-/-IL2rg-/- mice for human-cell fate
Zevaskyn
prademagene zamikeracel · COL7A1 (RV-modified keratinocyte sheets)Mouse only (immunodeficient mice with implanted human keratinocyte products); no relevant large-animal species
Zolgensma
onasemnogene abeparvovec · SMN1Mouse only for pivotal GLP tox (neonatal FVB); NHP only in non-GLP studies (later 6-month juvenile NHP study in label)