Adstiladrin
nadofaragene firadenovec · IFN-alpha2b (adenovirus, intravesical)Orthotopic mouse model of human bladder cancer: anti-tumor activity after intravesical rAd-IFN/Syn3
Glybera: animal efficacy model or human cells?
alipogene tiparvovec · LPL (AAV1)
Efficacy evidence
LPL-/- mice and LPL-deficient cats: triglyceride-lowering pharmacodynamic activity
“Overall, the applicant showed relevant pharmacodynamic activity of AMT-010 and AMT-011 in LPL-/- mice and/or cats.”
Why that model
Genetic LPL-deficient models available, but LPL-/- mice do not develop acute pancreatitis, the key human complication
“However, LPL-/- mice do not develop acute pancreatitis, which is the most severe complication observed in humans suffering from LPLD.”
Reviewer's view of the efficacy data
Long-lasting LPL expression with marked triglyceride lowering accepted as pharmacological surrogate for efficacy
“A single dose was able to induce a long-lasting expression of transgene, human LPL, which was associated with a clear effect to reduce raised triglycerides very markedly. This is considered to be an acceptable pharmacological surrogate for efficacy.”
Same question, other gene therapies
Beqvez
fidanacogene elaparvovec · Factor IXHemophilia B mice given BEQVEZ: liver hFIX-R338L expression and hemostatic FIX activity
Casgevy
exagamglogene autotemcel · BCL11A enhancer (CRISPR-Cas9, ex vivo HSC)Edited human CD34+ cells engrafted in NSG mice retained >90% on-target editing at 16 weeks
Elevidys
delandistrogene moxeparvovec · Micro-dystrophinRodent DMD models: mdx mice and Dmdmdx rats (force, muscle pathology, micro-dystrophin expression)
Fayuvi
rebisufligene etisparvovec · SGSH (AAV9)MPS IIIA mouse pharmacology study (survival, brain GAG, Morris water maze, GFAP, neuropathology); SGSH knock-out cells in vitro
Genglycos
pariglasgene brecaparvovec · G6PC (AAV8)G6PC-deficient GSDIa mouse model: dose-dependent increases in hepatic G6Pase activity and fasting glucose
Hemgenix
etranacogene dezaparvovec · Factor IXHemophilia B mouse (B6.129P2-F9tm1Dws) with predecessor vector AMT-060: dose-dependent liver transduction, hFIX protein and activity
Imlygic
talimogene laherparepvec · GM-CSF (oncolytic HSV-1)Syngeneic mouse melanoma (B16F10-muNectin1) with clinical virus: significant anti-tumour effect after one or three intratumoral doses
Itvisma
onasemnogene abeparvovec (intrathecal) · SMN1 (AAV9, intrathecal)SMA piglet model, IT research-grade vector (scAAV9.CBA.SMN): prevented hindlimb weakness and slowed disease progression
Kebilidi
eladocagene exuparvovec · AADCIn vitro studies in human cells (AADC expression and biological activity) only
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
voretigene neparvovec · RPE65RPE65-mutant dogs: improved pupillary responses, ERGs and visual behavior, reduced nystagmus
Lyfgenia
lovotibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)Transgenic SCD mice given marrow cells transduced with a related βA-T87Q vector: βA-T87Q expression and correction of sickling
Otarmeni
lunsotogene parvec · OTOF (AAV, intracochlear)Otof-Q828X homozygous deafness mouse: dose-dependent ABR threshold recovery with otoferlin expression in IHCs
Papzimeos
zopapogene imadenovec · HPV6/11 antigens (gorilla adenovirus)HPV antigen-specific T-cell responses in immunized healthy wild-type C57BL/6 mice; no disease model
Roctavian
valoctocogene roxaparvovec · Factor VIIIRag2-/- x FVIII-/- haemophilia A mice: blood loss and bleeding time almost corrected to wild-type levels
Skysona
elivaldogene autotemcel · ABCD1 (LVV, ex vivo HSC)Healthy-donor Lenti-D HSCs in myeloablated immunodeficient mice: bone marrow and brain engraftment with ABCD1 expression and ALDP production
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
Waskyra
etuvetidigene autotemcel · WAS (LVV, ex vivo HSC)WAS-deficient mice transplanted with WAS LVV-transduced murine Lin- BM cells: increased B cells, platelets, granulocytes; improved T, B and DC function
Zevaskyn
prademagene zamikeracel · COL7A1 (RV-modified keratinocyte sheets)Representative RVV-transduced keratinocyte grafts in mouse excisional wounds: cells stayed localized, Col7 expression up to 12 months
Zolgensma
onasemnogene abeparvovec · SMN1SMNdelta7 SMA mouse model: single IV clinical vector lots gave dose-dependent survival improvement
Zynteglo
betibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)β-thalassaemic mouse model given BB305 LVV-transduced mouse BMCs: correction of the β-thalassaemic phenotype