Actemra
tocilizumab · IL-6RCynomolgus monkey collagen-induced arthritis model
Penpulimab: animal efficacy model or human cells?
penpulimab · PD-1
Efficacy evidence
Human PD-1 knock-in mice (HuGEMM) bearing MC38 colon adenocarcinoma, dosed with penpulimab
“Given that pempulimab does not bind mouse PD-1, the Applicant investigated the in vivo antitumor activity of pempulimab in a human PD-1 knock-in genetically engineered mouse model (HuGEMM) implanted subcutaneously with MC38 mouse colon adenocarcinoma cells.”
Why that model
Penpulimab does not bind mouse PD-1, so a human PD-1 knock-in mouse model was used
“Given that pempulimab does not bind mouse PD-1, the Applicant investigated the in vivo antitumor activity of pempulimab in a human PD-1 knock-in genetically engineered mouse model (HuGEMM)”
Reviewer's view of the efficacy data
FDA: no outstanding pharmacology/toxicology issues preventing approval
“There are no outstanding issues from a pharmacology/toxicology perspective that would prevent the approval of penpulimab (either in combination with gemcitabine and cisplatin or carboplatin, or as a single agent) for the treatment of adult patients with non-keratinizing NPC.”
Same question, other monoclonal antibodies
Adakveo
crizanlizumab · P-selectinHuman cells in vitro: blockade of neutrophil rolling/adhesion and sickled red cell binding to human endothelium
Adbry
tralokinumab · IL-13In vivo type-2 inflammation models (IL-13-induced mouse, monkey allergen challenge); no AD model; AD support from in vitro human skin cells
Aduhelm
aducanumab · Aggregated amyloid-βTg2576 transgenic AD mouse with murine analog ch12F6A (plaque and insoluble Aβ reduction)
Aimovig
erenumab · CGRP receptorCapsaicin-induced dermal blood flow inhibition in normal cynomolgus monkeys; no animal migraine model
Ajovy
fremanezumab · CGRPRat post-concussion and medication-overuse headache models; vasodilation models in rat and cynomolgus monkey
Alhemo
concizumab · TFPIAntibody-induced (anti-FVIII) hemophilia A rabbit cuticle bleeding model: dose-dependent reduction in blood loss
Andembry
garadacimab · Factor XIIaCaptopril-induced edema in heterozygous C1-INH-deficient mice: garadacimab inhibited vascular permeability increase
Anthim
obiltoxaximab · B. anthracis PAInhalational anthrax (aerosol B. anthracis spores) in NZW rabbits and cynomolgus macaques
Arzerra
ofatumumab · CD20SCID mouse xenografts of human B-cell tumour lines treated with ofatumumab
Avastin
bevacizumab · VEGF-AHuman tumour xenografts in nude mice, mainly with murine parent A4.6.1; bevacizumab also inhibited breast, prostate and ovarian xenografts
Bavencio
avelumab · PD-L1Syngeneic MC38 colon cancer mouse model with avelumab
Benlysta
belimumab · BLyS (BAFF)B-cell reduction and inhibited splenocyte proliferation in normal mice and monkeys; no disease model
Beovu
brolucizumab · VEGF-ARodent ocular models: VEGF-induced retinal permeability (rat), oxygen-induced retinopathy (neonatal rat), laser-induced CNV (mouse)
Beyfortus
nirsevimab · RSV F proteinCotton rat RSV A2/B9320 challenge model with antibody 1G7 (IM prophylaxis 1 day before infection)
Bimzelx
bimekizumab · IL-17A/IL-17FIn vitro only: primary human dermal fibroblasts and keratinocytes; no in vivo pharmacodynamics
Briumvi
ublituximab · CD20In vivo B-cell depletion in mouse models clearing patient-derived B-CLL cells
Cablivi
caplacizumab · von Willebrand factor (A1 domain)Baboon model of acquired TTP induced by an inhibitory anti-ADAMTS13 antibody (preventive and therapeutic dosing)
Campath
alemtuzumab · CD52Lymphocyte depletion in huCD52 transgenic mice and cynomolgus monkeys
Cimzia
certolizumab pegol · TNF-αHuman TNFα challenge in normal mice and rabbits; transgenic mouse polyarthritis model (protection at 10 and 30 mg/kg)
Cinqair
reslizumab · IL-5Allergen-challenge eosinophilia models: OVA-sensitized mice and guinea pigs, Ascaris-challenged monkeys, antigen-challenged rabbits
Cosentyx
secukinumab · IL-17AMouse knee-joint inflammation and air pouch models driven by locally produced human IL-17A; no psoriasis-like disease model
Crysvita
burosumab · FGF23Hyp mouse (XLH model) treated with a murine anti-FGF23 antibody
Cyramza
ramucirumab · VEGFR2Surrogate DC101 in human gastric cancer xenografts (NCI-N87, MKN-45) and primary gastric tumor fragments in athymic mice
Danyelza
naxitamab · GD2Athymic nude mice bearing subcutaneous human neuroblastoma xenografts treated with naxitamab
Darzalex
daratumumab · CD38Human lymphoma xenografts in SCID mice (preventive and therapeutic), plus in vitro human/patient-derived cell assays
Dupixent
dupilumab · IL-4RaTransgenic mice expressing human IL-4 and IL-4Rα in type 2 immune response models; no atopic dermatitis model
Ebanga
ansuvimab · Zaire ebolavirus glycoproteinLethal EBOV Kikwit challenge in rhesus monkeys: single 50 mg/kg up to 5 days postchallenge prevented mortality
Ebglyss
lebrikizumab · IL-13Human IL-13-induced airway inflammation in C57BL/6 mice (lebrikizumab reduced inflammatory reactions)
Emgality
galcanezumab · CGRPCapsaicin-induced dermal blood flow increase in normal rats and cynomolgus monkeys
Empliciti
elotuzumab · SLAMF7Human myeloma xenografts (L363, OPM2) in immunodeficient mice treated with elotuzumab (HuLuc63)
Enflonsia
clesrovimab · RSV F protein (site IV)Cotton rat intranasal RSV A2 challenge model dosed with clesrovimab (0.03-2.5 mg/kg)
Enjaymo
sutimlimab · Complement C1sNear-complete classical complement inhibition (up to 98%) in cynomolgus monkeys at both dose levels
Enspryng
satralizumab · IL-6RNormal cynomolgus monkeys: inhibition of IL-6-stimulated CRP production and soluble IL-6R binding (vs tocilizumab)
Entyvio
vedolizumab · α4β7-integrinSpontaneous-colitis cotton-top tamarins treated with Act-1, the murine vedolizumab precursor (2.0 mg/kg for 8 days)
Erbitux
cetuximab · EGFRHuman tumour xenografts (GEO colon, renal, A431) in immunodeficient mice treated with cetuximab
Evenity
romosozumab · SclerostinOvariectomized rat and monkey models of postmenopausal osteoporosis treated with romosozumab
Evkeeza
evinacumab · ANGPTL3Evinacumab in hyperlipidemic mouse models (ApoE-/-, Ldlr-/-, db/db, high-fat diet) and normolipidemic mice
Exdensur
depemokimab · IL-5Prolonged blood eosinophil suppression in normal cynomolgus monkeys (39-week PK/PD study, 1 mg/kg)
Fasenra
benralizumab · IL-5RαNaive and allergen-challenged cynomolgus monkeys: eosinophil depletion in blood, bone marrow and BAL fluid
Gamifant
emapalumab · IFN-γPerforin-deficient mice infected with LCMV (HLH model) treated with surrogate antibody XMG1.2
Gazyva
obinutuzumab · CD20Human B-cell lymphoma xenografts (DLBCL, NHL, MCL) in SCID beige mice
Herceptin
trastuzumab · HER2Human HER2-overexpressing tumour xenografts (BT-474) in vivo; trastuzumab plus paclitaxel gave greatest regression
Humira
adalimumab · TNF-αHuman TNFα transgenic arthritis mice (Tg197, Tg5453); hTNFα-induced lethality (mice) and pyrexia (rabbits)
Hympavzi
marstacimab · TFPIHemophilia A (FVIII-deficient) and B (FIX-deficient) mouse models; blood loss reduced 76% and 65%
Ilaris
canakinumab · IL-1βCanakinumab inhibited human IL-1β-induced mouse joint inflammation, rat fever and mouse air-pouch neutrophil infiltration
Ilumya
tildrakizumab · IL-23 p19Mouse surrogate SCH-900598 in T-cell-dependent and anti-CD40 colitis models; unrelated anti-IL-23p19 mAb in psoriasis skin xenograft mice
Imaavy
nipocalimab · FcRnNipocalimab in humanized FcRn Tg32 mice: collagen antibody-induced arthritis and immune thrombocytopenia models
Imfinzi
durvalumab · PD-L1Durvalumab in A375 and HPAC human tumour xenografts with human CD4+/CD8+ T cells; HPAC max tumour growth inhibition 74%
Imjudo
tremelimumab · CTLA-4Surrogate anti-mouse CTLA-4 antibody in subcutaneous syngeneic mouse tumour models, alone and with anti-mouse PD-L1
Jemperli
dostarlimab · PD-1MC38 syngeneic mouse colon tumor model with anti-mouse PD-1 surrogate RMP1-14; dostarlimab tested in vitro only
Kevzara
sarilumab · IL-6RMouse collagen-induced arthritis with surrogate REGN844 (prophylactic); prevented joint inflammation and bone erosion
Keytruda
pembrolizumab · PD-1MC38 syngeneic mouse colon tumor model with hamster anti-mouse PD-1 surrogate J43
Kisunla
donanemab · Amyloid-β (N3pG)Aged PDAPP transgenic mice (amyloid plaques) treated with murine surrogate mE8c: dose- and effector-dependent plaque reduction
Lartruvo
olaratumab · PDGFRαHuman sarcoma xenografts (leiomyosarcoma, osteosarcoma) in nude mice treated with olaratumab, alone and with doxorubicin
Leqembi
lecanemab · Amyloid-β protofibrilsTg2576 and APPArcSwe Alzheimer's mice with murine analog mAb158; lecanemab tested in vitro
Libtayo
cemiplimab · PD-1Syngeneic colorectal tumor xenografts in huPD-1 knock-in mice treated with cemiplimab
Loqtorzi
toripalimab · PD-1MC38 colon tumors in human PD-1 knock-in mice; melanoma xenograft in NSG mice with CTL transfer
Lucentis
ranibizumab · VEGF-ALaser-induced choroidal neovascularisation (CNV) in monkeys; modified Miles vascular permeability assay
Margenza
margetuximab · HER2HER2+ human breast cancer xenografts in mice, including hCD16A knock-in transgenic mice
Monjuvi
tafasitamab · CD19SCID mouse subcutaneous xenografts of human Raji and RAMOS lymphoma; reduced tumor growth
Nemluvio
nemolizumab · IL-31RAClinical antibody in IL-31-induced itch model in cynomolgus monkeys; mouse surrogate BM095 in mite antigen-induced AD mouse model
Niktimvo
axatilimab · CSF-1RIn vitro human and monkey monocytes, CSF-1R-expressing CHO cells and human cancer cells; PD endpoints in monkey single- and repeat-dose studies
Nucala
mepolizumab · IL-5Acute Ascaris suum challenge asthma model in cynomolgus monkeys; reduced pulmonary eosinophilia
Ocrevus
ocrelizumab · CD20Human-derived cell lines in vitro; in vivo studies in cynomolgus monkeys only
Omvoh
mirikizumab · IL-23 p19Mouse surrogate antibody LSN2479016 in two murine IBD models (CD4+ T-cell transfer colitis)
Opdivo
nivolumab · PD-1Murine anti-PD-1 surrogate (4H2) in syngeneic mouse tumor models (MC38, Sa1N, J558 responsive)
Pasatru
garetosmab · Activin AGaretosmab reduced heterotopic ossification in two conditional knock-in FOP mouse models
Perjeta
pertuzumab · HER2Human tumor xenografts (breast, prostate, NSCLC, ovarian; HER2 low or high) in mice treated with pertuzumab
Piasky
crovalimab · Complement C5No PNH animal model; complement inhibition (CH50, free C5) in monkey PK/PD and repeat-dose studies plus in vitro RBC lysis
Portrazza
necitumumab · EGFRMouse xenografts of human NSCLC, pancreatic and colorectal tumour cell lines; tumour growth inhibition depending partly on EGFR status
Poteligeo
mogamulizumab · CCR4SCID mouse xenografts of human CTCL (HH) and ATL (TL-Om1) cell lines
Praluent
alirocumab · PCSK9APOE*Leiden.CETP mice on western diet, assessing lipid turnover and prevention of cardiovascular events
Praxbind
idarucizumab · DabigatranDabigatran-anticoagulated bleeding models: rat tail bleeding, mouse intracranial haemorrhage, pig liver trauma
Prolia
denosumab · RANKLOvariectomized cynomolgus monkey model of postmenopausal osteoporosis
Raxibacumab
raxibacumab · B. anthracis protective antigenInhalational anthrax spore challenge in rabbits and non-human primates, alone and with antibiotics
Remicade
infliximab · TNF-αHuman TNFα transgenic mouse models and rhTNFα-challenged normal mice
Repatha
evolocumab · PCSK9Cholesterol and LDL-C lowering in normal hamsters and monkeys
Rituxan
rituximab · CD20B-cell depletion in normal cynomolgus monkeys (peripheral blood and lymphatic tissues)
Rystiggo
rozanolixizumab · FcRnMouse surrogate anti-FcRn mAb in an immune thrombocytopenia (ITP) disease model
Saphnelo
anifrolumab · IFNAR1Mouse surrogate anti-IFNAR1 mAb in spontaneous SLE mouse model (prevented proteinuria)
Sarclisa
isatuximab · CD38SU-DHL-8 non-Hodgkin lymphoma xenograft in SCID mice (in vivo proof of concept)
Siliq
brodalumab · IL-17RAMouse anti-IL-17RA surrogate antibodies in a mouse skin-inflammation model
Simponi
golimumab · TNF-αMouse arthritis model: single golimumab dose (1-30 mg/kg) delayed onset of clinical symptoms
Simulect
basiliximab · IL-2Rα (CD25)In vitro IL-2 binding blockade on T-lymphocytes (human/primate cells) and human tissue binding; no in vivo model
Skyrizi
risankizumab · IL-23 p19Human IL-23-induced mouse ear thickening (skin inflammation) model; in vitro IL-23 signalling and IL-17 inhibition
Soliris
eculizumab · Complement C5Murine anti-rodent C5 surrogates in non-PNH mouse models (arthritis, lupus, airway inflammation, cardiac allograft)
Spevigo
spesolimab · IL-36RSurrogate BI 674304 in imiquimod-induced and IL-36-induced mouse skin inflammation models
Stelara
ustekinumab · IL-12/23 p40Marmoset experimental autoimmune encephalomyelitis (EAE) model with the clinical antibody
Sylvant
siltuximab · IL-6Mouse xenograft models of human IL-6-producing tumours (e.g. H460 lung) with siltuximab; no MCD model
Synagis
palivizumab · RSV F proteinCotton rat RSV infection model: lung virus titres reduced prophylactically and therapeutically at 5 mg/kg IM or IV
Takhzyro
lanadelumab · Plasma kallikreinCarrageenan-induced rat paw oedema: dose-dependent inhibition, max 73% (SC) at 30 mg/kg
Taltz
ixekizumab · IL-17ASurrogate anti-mouse IL-17 antibodies in mouse collagen-induced arthritis and EAE models
Tecentriq
atezolizumab · PD-L1Syngeneic mouse melanoma and colorectal tumour models with murine/human chimeric atezolizumab; tumour growth reduced by at least 80%
Tepezza
teprotumumab · IGF-1RHuman tumour xenografts in nude mice: single 6 mg/kg IP dose down-regulated tumour IGF-1R (target engagement, not a TED model)
Tevimbra
tislelizumab · PD-1Mouse xenograft tumour models engrafted with human PBMCs: anti-tumour efficacy against several tumour cell lines
Tezspire
tezepelumab · TSLPMouse surrogate M702 in OVA-induced asthma model: decreased airway hyperresponsiveness and BALF leukocytes
Tremfya
guselkumab · IL-23 p19rhIL-23 challenge in mice: guselkumab attenuated induced serum IL-1α and G-CSF increases
Trogarzo
ibalizumab · CD4SIV-infected rhesus monkeys: SIV viral load reduced up to day 10 despite neutralizing ADA
Tysabri
natalizumab · α4-integrinGuinea pig EAE (MS model): natalizumab 3 mg/kg s.c. had beneficial effects on active EAE
Tzield
teplizumab · CD3NOD mouse (spontaneous T1D) with anti-mouse CD3 surrogate: diabetes onset delayed ~5 weeks, incidence reduced ~30%
Ultomiris
ravulizumab · Complement C5NOD-scid mice given human C5: >3-fold longer half-life and prolonged haemolysis inhibition vs eculizumab; no disease model
Unituxin
dinutuximab · GD2Published SCID mouse xenografts: ch14.18 with human PBMCs and IL-2 prevented GD2+ melanoma growth
Unloxcyt
cosibelimab · PD-L1In vitro only: binding, PD-1 reporter and human mixed lymphocyte reaction (increased IFN-γ); no in vivo model
Uplizna
inebilizumab · CD19EAE and Sle1 autoimmune models in huCD19 transgenic mice: B-cell depletion, reduced autoantibodies and disease scores
Vectibix
panitumumab · EGFRTumour cell xenotransplants in mice: inhibition of tumour cell growth in vivo
Veopoz
pozelimab · Complement C5Ex vivo hemolysis inhibition in serum from pozelimab-treated C5 humanized mice and normal monkeys
Voyxact
sibeprenlimab · APRILgddY IgA nephropathy mouse model with mouse surrogate mAb 4540; IgA reduction in healthy monkeys with sibeprenlimab
Vyepti
eptinezumab · CGRPCapsaicin- or CGRP-induced dermal blood flow increase in rats, cynomolgus monkeys and rabbits
Vyloy
zolbetuximab · Claudin 18.2Mouse xenograft models of human gastric cancer
Xolair
omalizumab · IgESkin test reactivity in ragweed-sensitised cynomolgus monkeys; otherwise in vitro studies
Yartemlea
narsoplimab · MASP-2In vivo mouse model of TMA and ex vivo aHUS patient serum on human endothelial cells
Yervoy
ipilimumab · CTLA-4MC-38 colon carcinoma in human CTLA-4 transgenic mice
Zinbryta
daclizumab · IL-2Rα (CD25)In vitro inhibition of IL-2-induced proliferation and cytokine secretion in human and monkey primary lymphocytes
Zinplava
bezlotoxumab · C. difficile toxin BHamster and mouse C. difficile infection models with actoxumab+bezlotoxumab
Zynyz
retifanlimab · PD-1Retifanlimab binding to peripheral T cells (flow cytometry) in cynomolgus monkey studies