Adstiladrin
nadofaragene firadenovec · IFN-alpha2b (adenovirus, intravesical)Orthotopic mouse model of human bladder cancer: anti-tumor activity after intravesical rAd-IFN/Syn3
Waskyra: animal efficacy model or human cells?
etuvetidigene autotemcel · WAS (LVV, ex vivo HSC)
Efficacy evidence
WAS-deficient mice transplanted with WAS LVV-transduced murine Lin- BM cells: increased B cells, platelets, granulocytes; improved T, B and DC function
“In vivo pharmacology studies conducted using surrogate lineage negative (Lin-) BM cells transduced with WAS LVV transplanted into WAS-deficient mice demonstrated increased B cell, platelet, and granulocyte cell counts and improved T cell, B cell and DC function.”
Why that model
Autologous human cells cannot be used in animal models, limiting nonclinical studies
“The impossibility of using autologous human cells in animal models limits the scope of possible nonclinical studies.”
Reviewer's view of the efficacy data
Models considered acceptable as surrogate of Waskyra-transduced HSPCs
“The pharmacology, toxicology and genotoxicity of Waskyra were evaluated in vitro and in vivo. The models used were considered acceptable as surrogate of HPSC transduced with Waskyra.”
Same question, other gene therapies
Beqvez
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Genglycos
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Glybera
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Hemgenix
etranacogene dezaparvovec · Factor IXHemophilia B mouse (B6.129P2-F9tm1Dws) with predecessor vector AMT-060: dose-dependent liver transduction, hFIX protein and activity
Imlygic
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Itvisma
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Kebilidi
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Kresladi
marnetegragene autotemcel · ITGB2 (LVV, ex vivo HSC)CD18HYP and CD18KO LAD-I mice given vector-transduced murine Lin- cells: engraftment and enhanced neutrophil extravasation to inflamed sites
Lenmeldy
atidarsagene autotemcel · ARSA (LVV, ex vivo HSC)As2-/- MLD mice given ARSA-LV murine HSPCs: improved motor conduction, rotarod coordination and neuropathology vs GFP-LV controls
Luxturna
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Lyfgenia
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Papzimeos
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Roctavian
valoctocogene roxaparvovec · Factor VIIIRag2-/- x FVIII-/- haemophilia A mice: blood loss and bleeding time almost corrected to wild-type levels
Skysona
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Strimvelis
autologous CD34+ cells transduced with ADA (no INN) · ADA (gamma-retroviral, ex vivo HSC)SCID-hu xenograft mice: transduced CD34+ cells engrafted and produced vector-marked, transgene-expressing T and B cells
Tudriqev
vusolimogene oderparepvec · GALV-GP + GM-CSF (oncolytic HSV-1)Human tumor cell lines in vitro; murine surrogate mRP1 in syngeneic lymphoma, colorectal and melanoma tumor-bearing mice
Vyjuvek
beremagene geperpavec · COL7A1 (HSV-1, topical)Hypomorphic DEB mouse model and wild-type BALB/c mice: dermal transduction, COL7 expression, anchoring fibrils
Zevaskyn
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Zolgensma
onasemnogene abeparvovec · SMN1SMNdelta7 SMA mouse model: single IV clinical vector lots gave dose-dependent survival improvement
Zynteglo
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