Aimovig (erenumab): animal efficacy model or human cells?

Atlas/Monoclonal antibodies/Aimovig/Efficacy evidence

Aimovig: animal efficacy model or human cells?

erenumab · CGRP receptor

Efficacy evidence

Capsaicin-induced dermal blood flow inhibition in normal cynomolgus monkeys; no animal migraine model

“In vivo activity was demonstrated in a cynomolgus model of capsaicin induced increase in dermal blood flow, an effect mediated at least partly by CGRP. There are no animal migraine models.”

✓ VerifiedEMA assessment report, p. 27Source ↗

Why that model

No animal migraine models exist, so therapeutic evidence derives from clinical data

“There are no animal migraine models. Therefore, all evidence for a therapeutic effect is derived from clinical data.”

✓ VerifiedEMA assessment report, p. 27Source ↗

Reviewer's view of the efficacy data

EMA: primary pharmacodynamics programme considered appropriate

“The primary pharmacodynamics program has been appropriate.”

✓ VerifiedEMA assessment report, p. 31Source ↗

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bimekizumab · IL-17A/IL-17F

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In vivo B-cell depletion in mouse models clearing patient-derived B-CLL cells

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caplacizumab · von Willebrand factor (A1 domain)

Baboon model of acquired TTP induced by an inhibitory anti-ADAMTS13 antibody (preventive and therapeutic dosing)

Campath

alemtuzumab · CD52

Lymphocyte depletion in huCD52 transgenic mice and cynomolgus monkeys

Cimzia

certolizumab pegol · TNF-α

Human TNFα challenge in normal mice and rabbits; transgenic mouse polyarthritis model (protection at 10 and 30 mg/kg)

Cinqair

reslizumab · IL-5

Allergen-challenge eosinophilia models: OVA-sensitized mice and guinea pigs, Ascaris-challenged monkeys, antigen-challenged rabbits

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Mouse knee-joint inflammation and air pouch models driven by locally produced human IL-17A; no psoriasis-like disease model

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ramucirumab · VEGFR2

Surrogate DC101 in human gastric cancer xenografts (NCI-N87, MKN-45) and primary gastric tumor fragments in athymic mice

Danyelza

naxitamab · GD2

Athymic nude mice bearing subcutaneous human neuroblastoma xenografts treated with naxitamab

Darzalex

daratumumab · CD38

Human lymphoma xenografts in SCID mice (preventive and therapeutic), plus in vitro human/patient-derived cell assays

Dupixent

dupilumab · IL-4Ra

Transgenic mice expressing human IL-4 and IL-4Rα in type 2 immune response models; no atopic dermatitis model

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Lethal EBOV Kikwit challenge in rhesus monkeys: single 50 mg/kg up to 5 days postchallenge prevented mortality

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lebrikizumab · IL-13

Human IL-13-induced airway inflammation in C57BL/6 mice (lebrikizumab reduced inflammatory reactions)

Emgality

galcanezumab · CGRP

Capsaicin-induced dermal blood flow increase in normal rats and cynomolgus monkeys

Empliciti

elotuzumab · SLAMF7

Human 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 C1s

Near-complete classical complement inhibition (up to 98%) in cynomolgus monkeys at both dose levels

Enspryng

satralizumab · IL-6R

Normal cynomolgus monkeys: inhibition of IL-6-stimulated CRP production and soluble IL-6R binding (vs tocilizumab)

Entyvio

vedolizumab · α4β7-integrin

Spontaneous-colitis cotton-top tamarins treated with Act-1, the murine vedolizumab precursor (2.0 mg/kg for 8 days)

Erbitux

cetuximab · EGFR

Human tumour xenografts (GEO colon, renal, A431) in immunodeficient mice treated with cetuximab

Evenity

romosozumab · Sclerostin

Ovariectomized rat and monkey models of postmenopausal osteoporosis treated with romosozumab

Evkeeza

evinacumab · ANGPTL3

Evinacumab in hyperlipidemic mouse models (ApoE-/-, Ldlr-/-, db/db, high-fat diet) and normolipidemic mice

Exdensur

depemokimab · IL-5

Prolonged blood eosinophil suppression in normal cynomolgus monkeys (39-week PK/PD study, 1 mg/kg)

Fasenra

benralizumab · IL-5Rα

Naive and allergen-challenged cynomolgus monkeys: eosinophil depletion in blood, bone marrow and BAL fluid

Gamifant

emapalumab · IFN-γ

Perforin-deficient mice infected with LCMV (HLH model) treated with surrogate antibody XMG1.2

Gazyva

obinutuzumab · CD20

Human B-cell lymphoma xenografts (DLBCL, NHL, MCL) in SCID beige mice

Herceptin

trastuzumab · HER2

Human HER2-overexpressing tumour xenografts (BT-474) in vivo; trastuzumab plus paclitaxel gave greatest regression

Humira

adalimumab · TNF-α

Human TNFα transgenic arthritis mice (Tg197, Tg5453); hTNFα-induced lethality (mice) and pyrexia (rabbits)

Hympavzi

marstacimab · TFPI

Hemophilia A (FVIII-deficient) and B (FIX-deficient) mouse models; blood loss reduced 76% and 65%

Ilaris

canakinumab · IL-1β

Canakinumab inhibited human IL-1β-induced mouse joint inflammation, rat fever and mouse air-pouch neutrophil infiltration

Ilumya

tildrakizumab · IL-23 p19

Mouse surrogate SCH-900598 in T-cell-dependent and anti-CD40 colitis models; unrelated anti-IL-23p19 mAb in psoriasis skin xenograft mice

Imaavy

nipocalimab · FcRn

Nipocalimab in humanized FcRn Tg32 mice: collagen antibody-induced arthritis and immune thrombocytopenia models

Imfinzi

durvalumab · PD-L1

Durvalumab in A375 and HPAC human tumour xenografts with human CD4+/CD8+ T cells; HPAC max tumour growth inhibition 74%

Imjudo

tremelimumab · CTLA-4

Surrogate anti-mouse CTLA-4 antibody in subcutaneous syngeneic mouse tumour models, alone and with anti-mouse PD-L1

Jemperli

dostarlimab · PD-1

MC38 syngeneic mouse colon tumor model with anti-mouse PD-1 surrogate RMP1-14; dostarlimab tested in vitro only

Kevzara

sarilumab · IL-6R

Mouse collagen-induced arthritis with surrogate REGN844 (prophylactic); prevented joint inflammation and bone erosion

Keytruda

pembrolizumab · PD-1

MC38 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 · PDGFRα

Human sarcoma xenografts (leiomyosarcoma, osteosarcoma) in nude mice treated with olaratumab, alone and with doxorubicin

Leqembi

lecanemab · Amyloid-β protofibrils

Tg2576 and APPArcSwe Alzheimer's mice with murine analog mAb158; lecanemab tested in vitro

Libtayo

cemiplimab · PD-1

Syngeneic colorectal tumor xenografts in huPD-1 knock-in mice treated with cemiplimab

Loqtorzi

toripalimab · PD-1

MC38 colon tumors in human PD-1 knock-in mice; melanoma xenograft in NSG mice with CTL transfer

Lucentis

ranibizumab · VEGF-A

Laser-induced choroidal neovascularisation (CNV) in monkeys; modified Miles vascular permeability assay

Margenza

margetuximab · HER2

HER2+ human breast cancer xenografts in mice, including hCD16A knock-in transgenic mice

Monjuvi

tafasitamab · CD19

SCID mouse subcutaneous xenografts of human Raji and RAMOS lymphoma; reduced tumor growth

Nemluvio

nemolizumab · IL-31RA

Clinical antibody in IL-31-induced itch model in cynomolgus monkeys; mouse surrogate BM095 in mite antigen-induced AD mouse model

Niktimvo

axatilimab · CSF-1R

In 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-5

Acute Ascaris suum challenge asthma model in cynomolgus monkeys; reduced pulmonary eosinophilia

Ocrevus

ocrelizumab · CD20

Human-derived cell lines in vitro; in vivo studies in cynomolgus monkeys only

Omvoh

mirikizumab · IL-23 p19

Mouse surrogate antibody LSN2479016 in two murine IBD models (CD4+ T-cell transfer colitis)

Opdivo

nivolumab · PD-1

Murine anti-PD-1 surrogate (4H2) in syngeneic mouse tumor models (MC38, Sa1N, J558 responsive)

Pasatru

garetosmab · Activin A

Garetosmab reduced heterotopic ossification in two conditional knock-in FOP mouse models

Penpulimab

penpulimab · PD-1

Human PD-1 knock-in mice (HuGEMM) bearing MC38 colon adenocarcinoma, dosed with penpulimab

Perjeta

pertuzumab · HER2

Human tumor xenografts (breast, prostate, NSCLC, ovarian; HER2 low or high) in mice treated with pertuzumab

Piasky

crovalimab · Complement C5

No PNH animal model; complement inhibition (CH50, free C5) in monkey PK/PD and repeat-dose studies plus in vitro RBC lysis

Portrazza

necitumumab · EGFR

Mouse xenografts of human NSCLC, pancreatic and colorectal tumour cell lines; tumour growth inhibition depending partly on EGFR status

Poteligeo

mogamulizumab · CCR4

SCID mouse xenografts of human CTCL (HH) and ATL (TL-Om1) cell lines

Praluent

alirocumab · PCSK9

APOE*Leiden.CETP mice on western diet, assessing lipid turnover and prevention of cardiovascular events

Praxbind

idarucizumab · Dabigatran

Dabigatran-anticoagulated bleeding models: rat tail bleeding, mouse intracranial haemorrhage, pig liver trauma

Prolia

denosumab · RANKL

Ovariectomized cynomolgus monkey model of postmenopausal osteoporosis

Raxibacumab

raxibacumab · B. anthracis protective antigen

Inhalational anthrax spore challenge in rabbits and non-human primates, alone and with antibiotics

Remicade

infliximab · TNF-α

Human TNFα transgenic mouse models and rhTNFα-challenged normal mice

Repatha

evolocumab · PCSK9

Cholesterol and LDL-C lowering in normal hamsters and monkeys

Rituxan

rituximab · CD20

B-cell depletion in normal cynomolgus monkeys (peripheral blood and lymphatic tissues)

Rystiggo

rozanolixizumab · FcRn

Mouse surrogate anti-FcRn mAb in an immune thrombocytopenia (ITP) disease model

Saphnelo

anifrolumab · IFNAR1

Mouse surrogate anti-IFNAR1 mAb in spontaneous SLE mouse model (prevented proteinuria)

Sarclisa

isatuximab · CD38

SU-DHL-8 non-Hodgkin lymphoma xenograft in SCID mice (in vivo proof of concept)

Siliq

brodalumab · IL-17RA

Mouse anti-IL-17RA surrogate antibodies in a mouse skin-inflammation model

Simponi

golimumab · TNF-α

Mouse 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 p19

Human IL-23-induced mouse ear thickening (skin inflammation) model; in vitro IL-23 signalling and IL-17 inhibition

Soliris

eculizumab · Complement C5

Murine anti-rodent C5 surrogates in non-PNH mouse models (arthritis, lupus, airway inflammation, cardiac allograft)

Spevigo

spesolimab · IL-36R

Surrogate BI 674304 in imiquimod-induced and IL-36-induced mouse skin inflammation models

Stelara

ustekinumab · IL-12/23 p40

Marmoset experimental autoimmune encephalomyelitis (EAE) model with the clinical antibody

Sylvant

siltuximab · IL-6

Mouse xenograft models of human IL-6-producing tumours (e.g. H460 lung) with siltuximab; no MCD model

Synagis

palivizumab · RSV F protein

Cotton rat RSV infection model: lung virus titres reduced prophylactically and therapeutically at 5 mg/kg IM or IV

Takhzyro

lanadelumab · Plasma kallikrein

Carrageenan-induced rat paw oedema: dose-dependent inhibition, max 73% (SC) at 30 mg/kg

Taltz

ixekizumab · IL-17A

Surrogate anti-mouse IL-17 antibodies in mouse collagen-induced arthritis and EAE models

Tecentriq

atezolizumab · PD-L1

Syngeneic mouse melanoma and colorectal tumour models with murine/human chimeric atezolizumab; tumour growth reduced by at least 80%

Tepezza

teprotumumab · IGF-1R

Human 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-1

Mouse xenograft tumour models engrafted with human PBMCs: anti-tumour efficacy against several tumour cell lines

Tezspire

tezepelumab · TSLP

Mouse surrogate M702 in OVA-induced asthma model: decreased airway hyperresponsiveness and BALF leukocytes

Tremfya

guselkumab · IL-23 p19

rhIL-23 challenge in mice: guselkumab attenuated induced serum IL-1α and G-CSF increases

Trogarzo

ibalizumab · CD4

SIV-infected rhesus monkeys: SIV viral load reduced up to day 10 despite neutralizing ADA

Tysabri

natalizumab · α4-integrin

Guinea pig EAE (MS model): natalizumab 3 mg/kg s.c. had beneficial effects on active EAE

Tzield

teplizumab · CD3

NOD mouse (spontaneous T1D) with anti-mouse CD3 surrogate: diabetes onset delayed ~5 weeks, incidence reduced ~30%

Ultomiris

ravulizumab · Complement C5

NOD-scid mice given human C5: >3-fold longer half-life and prolonged haemolysis inhibition vs eculizumab; no disease model

Unituxin

dinutuximab · GD2

Published SCID mouse xenografts: ch14.18 with human PBMCs and IL-2 prevented GD2+ melanoma growth

Unloxcyt

cosibelimab · PD-L1

In vitro only: binding, PD-1 reporter and human mixed lymphocyte reaction (increased IFN-γ); no in vivo model

Uplizna

inebilizumab · CD19

EAE and Sle1 autoimmune models in huCD19 transgenic mice: B-cell depletion, reduced autoantibodies and disease scores

Vectibix

panitumumab · EGFR

Tumour cell xenotransplants in mice: inhibition of tumour cell growth in vivo

Veopoz

pozelimab · Complement C5

Ex vivo hemolysis inhibition in serum from pozelimab-treated C5 humanized mice and normal monkeys

Voyxact

sibeprenlimab · APRIL

gddY IgA nephropathy mouse model with mouse surrogate mAb 4540; IgA reduction in healthy monkeys with sibeprenlimab

Vyepti

eptinezumab · CGRP

Capsaicin- or CGRP-induced dermal blood flow increase in rats, cynomolgus monkeys and rabbits

Vyloy

zolbetuximab · Claudin 18.2

Mouse xenograft models of human gastric cancer

Xolair

omalizumab · IgE

Skin test reactivity in ragweed-sensitised cynomolgus monkeys; otherwise in vitro studies

Yartemlea

narsoplimab · MASP-2

In vivo mouse model of TMA and ex vivo aHUS patient serum on human endothelial cells

Yervoy

ipilimumab · CTLA-4

MC-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 B

Hamster and mouse C. difficile infection models with actoxumab+bezlotoxumab

Zynyz

retifanlimab · PD-1

Retifanlimab binding to peripheral T cells (flow cytometry) in cynomolgus monkey studies

Summary across all 117 monoclonal antibodies →