Actemra
tocilizumab · IL-6RCynomolgus monkey collagen-induced arthritis model
Niktimvo: animal efficacy model or human cells?
axatilimab · CSF-1R
Efficacy evidence
In vitro human and monkey monocytes, CSF-1R-expressing CHO cells and human cancer cells; PD endpoints in monkey single- and repeat-dose studies
“Primary PD studies and studies to characterize the antibody and its mechanism of action were conducted in vitro in human and cynomolgus monkey monocytes, CHO cells expressing the CSF-1R extracellular domain, and human cancer cells. Additionally, PD endpoints were incorporated into single-and repeat-dose studies in cynomolgus monkeys.”
Why that model
Monkey is the only toxicology species in which axatilimab binds CSF-1R and blocks CSF-1 signaling
“The in vivo toxicology of axatilimab was assessed in the cynomolgus monkey, the only toxicology species in which axatilimab binds to CSF-1R and blocks CSF-1-mediated signaling of the receptor.”
Reviewer's view of the efficacy data
FDA generally agreed with the applicant's primary pharmacology assessment
“The Agency generally agrees with the Applicant’s assessment of the primary pharmacology studies as described above.”
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
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
Penpulimab
penpulimab · PD-1Human PD-1 knock-in mice (HuGEMM) bearing MC38 colon adenocarcinoma, dosed with penpulimab
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