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Precedia/Gene therapy/Hemgenix/Test article

Hemgenix: was the clinical lot tested, or a surrogate or earlier version?

etranacogene dezaparvovec · Factor IX
Check my plan vs. these
Test article vs clinical lot
Programme initiated with predecessor AMT-060, same vector backbone but lacking the 2-nucleotide change giving the Padua FIX variant. Bridging: Predecessor and clinical vector showed a comparable safety profile when tested side-by-side in mice and NHPs
“The non-clinical development programme was initiated with AMT-060, which has a similar vector backbone as etranacogene dezaparvovec (AMT-061), but lacks the 2-nucleotide change in the hFIX coding sequence (enhancing the FIX activity of Padua FIX variant).”
✓ VerifiedEMA assessment report, p. 24Source ↗
Genetically modified?
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.
Vector and route
AAV5-based gene therapy, single intravenous infusion
“HEMGENIX is an adeno-associated virus serotype 5 (AAV5) based gene therapy designed to deliver a copy of a gene encoding the Padua variant of human coagulation Factor IX (hFIX-Padua). Single intravenous infusion of HEMGENIX results in cell transduction and increase in circulating Factor IX activity in patients with Hemophilia B.”
✓ VerifiedUS prescribing informationSource ↗
First approval
2022 (FDA)
“Initial U.S. Approval: 2022”
✓ VerifiedUS prescribing informationSource ↗

Same question, other gene therapies

Adstiladrin

nadofaragene firadenovec · IFN-alpha2b (adenovirus, intravesical)
Several older rAd-IFN and Syn3NODA DS batches; not all representative of the clinical/commercial manufacturing process. Bridging: Quality data for some batches provided on request; considered supportive of the nonclinical profile

Beqvez

fidanacogene elaparvovec · Factor IX
Several toxicology studies used a closely related predecessor product, AAVRh74var-Padua, similar to BEQVEZ. Bridging: Batches used in the pivotal nonclinical biodistribution and toxicity/genotoxicity testing considered representative of clinical batches

Casgevy

exagamglogene autotemcel · BCL11A enhancer (CRISPR-Cas9, ex vivo HSC)
Non-GMP lots from three healthy donors made with the same process and manufacturer as the GMP clinical material. Bridging: Toxicology lots were manufactured in a non-GMP facility using the same process and same manufacturer as for GMP material

Elevidys

delandistrogene moxeparvovec · Micro-dystrophin
Nonclinical material from Process A (Nationwide Children’s), Process B at ThermoFisher and Process B at Catalent. Bridging: Process A and Process B products not analytically comparable; commercial product is Process B (Catalent)

Fayuvi

rebisufligene etisparvovec · SGSH (AAV9)
Definitive GLP safety and biodistribution studies and all clinical trials used FAYUVI manufactured under GMP conditions via Process A. Bridging: In vivo pharmacology studies bridged in vivo potency between the clinical Process A material and the later manufacturing process

Genglycos

pariglasgene brecaparvovec · G6PC (AAV8)
Clinical vector DTX401 in toxicology studies; earlier vector versions encoding the same protein only in pharmacology Studies 1–4. Bridging: Titers from the initial assay converted to the final titer method by a conversion factor; doses reported as equivalents

Glybera

alipogene tiparvovec · LPL (AAV1)
Plasmid-derived AMT-010 batches and the baculovirus-derived commercial product AMT-011 both used in non-clinical studies. Bridging: AMT-011 qualified independently of AMT-010 on non-clinical data; toxicology and pharmacology studies were repeated with AMT-011

Imlygic

talimogene laherparepvec · GM-CSF (oncolytic HSV-1)
Process B (earlier process) material in toxicology studies; Phase III and commercial product made by Process C. Bridging: Comparability between batches from the different manufacturing processes demonstrated

Itvisma

onasemnogene abeparvovec (intrathecal) · SMN1 (AAV9, intrathecal)
Research grade lots scAAV9.CBA.SMN, OAV101 and OAV101B used in the nonclinical programme. Bridging: Among the research lots, OAV101B had specifications most comparable to the clinical product

Kebilidi

eladocagene exuparvovec · AADC
Nonclinical studies used clinical lots 2004-101 and PBR-0045-001, not the intended commercial formulation. Bridging: Comparability of the clinical lots to lots made using the intended commercial process was provided

Kresladi

marnetegragene autotemcel · ITGB2 (LVV, ex vivo HSC)
Surrogate murine Lin- HSPCs transduced with the clinical vector used for the definitive in vivo toxicology and biodistribution studies. Bridging: All cells were transduced with the clinical vector, Chim-CD18-WPRE LV, which is used to produce RP-L201

Lenmeldy

atidarsagene autotemcel · ARSA (LVV, ex vivo HSC)
Murine Lin- HSPCs from As2-/- mice and healthy human HSPCs transduced with ARSA LVV used for most nonclinical studies. Bridging: Remaining nonclinical studies used the clinical LVV, while some studies used vector versions with WPRE or an HA epitope tag

Luxturna

voretigene neparvovec · RPE65
A precursor AAV2-hRPE65v2 vector product was used in normal-sighted dog studies at 1.5 x 1012 vg/eye. Bridging: Commercial lot shown comparable to the clinical material by lot release data and side-by-side comparability testing

Lyfgenia

lovotibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)
Murine bone marrow cells transduced with BB305 used in the primary and secondary transplantation studies, not patient CD34+ cells

Otarmeni

lunsotogene parvec · OTOF (AAV, intracochlear)
Non-GMP DB-OTO lot B564TOXP1 used in all three GLP studies; clinical product manufactured under GMP. Bridging: Nonclinical material judged comparable to the clinical investigational product based on process consistency

Papzimeos

zopapogene imadenovec · HPV6/11 antigens (gorilla adenovirus)
Research-grade lot PRGN-2012 of the clinical vector. Bridging: Adenovirus and fusion protein stated to be identical to the clinical product

Roctavian

valoctocogene roxaparvovec · Factor VIII
One mouse study used a batch from early research process B, not representative of the commercial formulation; later studies used clinical-like lots. Bridging: Lots manufactured by the commercial process reported comparable to lots produced with earlier processes

Skysona

elivaldogene autotemcel · ABCD1 (LVV, ex vivo HSC)
Healthy-donor CD34+ HSCs transduced with the same Lenti-D LVV used to produce the clinical product, not patient cells. Bridging: All cells were transduced with the same LVV, Lenti-D, that is used to produce eli-cel

Strimvelis

autologous CD34+ cells transduced with ADA (no INN) · ADA (gamma-retroviral, ex vivo HSC)
CD34+ cells from healthy human umbilical cord blood transduced with the GSK3336223 vector, used instead of patient cells. Bridging: The test item was accepted as representative of Strimvelis

Tudriqev

vusolimogene oderparepvec · GALV-GP + GM-CSF (oncolytic HSV-1)
Clinical product TUDRIQEV in tumor-bearing mice; murine surrogate mRP1 in healthy rats. Bridging: Clinical-site and commercial-site (Framingham) batches compared in tumor-bearing mice; no differences in toxicology or biodistribution

Vyjuvek

beremagene geperpavec · COL7A1 (HSV-1, topical)
Early-phase nonclinical studies used the early (Phase 1/2) production process; late-phase nonclinical studies used the Phase 3 process. Bridging: In vivo comparability study (KB103-IVV-010) in immunocompetent mice comparing batches from the two processes

Waskyra

etuvetidigene autotemcel · WAS (LVV, ex vivo HSC)
Mouse surrogate: lineage-deficient HSPCs transduced with either the w1.6W or the clinical w1.6W_mut6 vector. Bridging: The clinical w1.6W_mut6 vector was used alongside the earlier w1.6W vector in both mouse models

Zevaskyn

prademagene zamikeracel · COL7A1 (RV-modified keratinocyte sheets)
Representative nonclinical product: RVV-transduced human keratinocytes (cells alone) on human acellular dermal matrix, implanted into mouse wounds

Zolgensma

onasemnogene abeparvovec · SMN1
The two 12-week GLP studies used process B material; all other safety studies used pre-process A batch material. Bridging: Current-process lots comparable to the initial clinical lot, including potency-to-vector-genome ratio and survival in a mouse SMA model

Zynteglo

betibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)
Surrogates: BB305 LVV-transduced thalassaemic mouse bone marrow cells or healthy human donor HSCs, not patient cells. Bridging: Surrogate test articles were transduced with BB305 LVV and administered to beta-thalassaemic and NSG mice

Summary across all 26 gene therapies →