Table 10.
Clinical-stage antibodies and Fc-fusion proteins repurposed as palliative treatment for COVID-19
| Drug or candidate | Sponsor | COVID-19 most advanced status | COVID-19 clinical trial(s)a | Molecular target | Indication (non-COVID-19) |
Development Stage (US-FDA) | Format/Description |
|---|---|---|---|---|---|---|---|
| Alzumab (itolizumab) | Biocon (India) | EUA granted in India July 2020b | NA | CD6 | PsO | Approved in India, Jan 2013 | Humanized IgG1κ |
|
Actemra®; (RoACTEMRA® in EU) (Tocilizumab) |
Roche/Chugai/Genentech |
UK EUA 1/8/21; US-FDA EUA 6/24/21; WHO EUA 7/7/21; EC EUA 12/7/21 |
IL-6R (CD126) | CaD, RA |
US-FDA approved 1/09/10 |
Humanized IgG1κ | |
| Kevzara® (Sarilumab) | Sanofi/Regeneron |
UK EUA 1/8/21; WHO EUA 7/7/21 |
NCT04386239 | IL-6R (CD126) | RA |
US-FDA approved 5/22/17 |
Human IgG1κ |
|
Lenzilumab (KB003) |
Humanigen, Inc. | US-FDA EUA rejectedc; UK granted speedy review | NCT04583969 | GM-CSF | CMML, JMML | Phase III | Humanized IgG1κ |
| Ilaris® Canakinumab | Novartis |
Phase III (R) d Phase II (C) |
IL-1β | CAPS |
FDA Approved 06/19/09 |
Human IgG1κ | |
|
Ultomiris® (Ravulizumab-cwvz) |
Alexion Pharma | Phase III (R) | Complement C5 | PNH, CMD | FDA approved 12/21/18 | Humanized IgG2/4κ hybrid, modified Fc; Xencor Xtend HLE | |
|
Takhzyro® (Lanadelumab-flyo) |
Shire/Dyax | Phase III (ANR) | NCT04590586 | pKal | HAE | FDA approved 8/23/18 | Human IgG1κ |
| Avastin® (Bevacizumab) | Genentech | Phase III (NYR) | VEGF | CRC | FDA approved 02/26/04 | Humanized IgG1κ, | |
| Remicade® (Infliximab) | Johnson & Johnson | Phase II/III (R) | TNF-α | CrD, RA, 14 other indications | FDA approved 8/24/98 | Chimeric IgG1κ | |
|
Mavrilimumab (KPL-301) |
Kiniksa Phar-maceuticals | Phase II/III (R) | NCT04447469 | GM-CSF-Rα | GCA | Phase IIb/III | Human IgG4κ |
| TJM2 (aka TJ003234) | I-Mab Biopharma | Phase II/III (R) | NCT04341116 | GM-CSF | RA | Phase II/III | Humanized IgG1 |
|
Gimsilumab (KIN-1901) |
Kinevant Sciences GmbH | Phase II (C) | NCT04351243 | GM-CSF | RA | Phase II | Human IgG1κ |
|
Otilimab (GSK3196165) |
GSK/MorphoSys | Phase II (ANR) (D) | NCT04376684 | GM-CSF | RA, MS, OA | Phase III | Human IgG1κ |
| CERC-002 (AEVI-002, MDGN-002) f | Cerecor, Inc | Phase II (C, FTD) | NCT04412057 | LIGHT (TNFSF14) | CrD | Phase I | Fully human IgG4 |
|
Garadacimab (CSL312) |
CSL Behring | Phase II (C) | NCT04409509 | Factor XIIa antagonist | HAE, PICC-ADVT | Phase III | Human IgG4κ |
| Soliris® (Eculizumab) | Alexion Pharma | Phase II (R) | Complement C5 | PNH, aHUS | FDA approved 03/16/07 | Humanized IgG2/4κ hybrid, modified Fc | |
|
Avdoralimab (IPH5401) |
Innate Pharma/Novo Nordisk | Phase II (R) | C5a receptor (C5aR1) | INFL | Phase II | Human IgG1 | |
|
Narsoplimab (OMS721) |
Omeros | Phase II (R) | NCT04488081 | MASP-2 | HSCT-TMA, AHUS |
Phase III – BLA submitted |
Human IgG4κ |
|
Dupixent® (dupilumab) |
Regeneron/Sanofi | Phase II (R) | NCT04920916 | IL-4Rα | AD, asthma |
FDA Approved 3/28/17 |
Human IgG4κ-S/P; hinge modified |
|
Sylvant® (siltuximab) |
Fundacion Clinic per a la Recerca Biomédica | Phase II (R) | NCT04329650 | IL-6 | MCD |
FDA approved 4/23/14 |
Chimeric IgG1κ |
|
Clazakizumab (ALD518) |
CSL Behring | Phase II (R) |
NCT04363502 |
IL-6 | KTR | Phase III |
Humanized IgG1κ, non-glycosylated |
|
Olokizumab (CDP-6038) |
RPharm | Unstated (C) | NCT05196477 | IL-6 | RA | Phase III | Humanized IgG4κ |
|
BMS-986253 HuMax® IL-8 (MDX-018) |
BMS /Genmab/Cormorant Pharmaceuticals | Phase II (R) | NCT04347226 | IL-8 | Cancer | Phase II | Human IgG |
| hzVSF-v13 | ImmuneMed, Inc. | Phase II (R) | Vimentin ectodomain | Viral diseases | Phase II | Humanized IgG4 | |
|
Efineptakin alfa (Hyleukin-7; GX-17; NT-I7; rhIL-7-hyFc) |
NeoImmune-Tech/I-Mab | Phase II (R) | NCT04810637 | IL-7 receptor | HPV, GB, PML, MMel | Phase I/II | Fc fusion protein; Human IL-7 fused to a hybrid Fc (hyFc). |
|
Monalizumab (IPH2201) |
MedImmune/ Innate Pharma/Novo Nordisk |
Phase II (R) | NCT04333914 | NKG2A | INFL | Phase III | Humanized IgG4 |
| IC14 | Implicit Bioscience | Phase II (R) | CD14 | ALS, MND | Phase I | Chimeric IgG | |
|
Leronlimabe (PRO140) |
CytoDyn |
Phase III (NYR) Phase II (R) |
CCR5 | HIV, TNBC, NASH |
Phase II/III BLA submitted |
Humanized IgG4κ | |
| Opdivo® (nivolumab) | BMS | Phase II (NYR) | NCT04413838 | PD-1 | MMel | FDA approved 12/22/14 | Human IgG4κ |
| Simulect® (basiliximab) | Fort Worth Clinical Sciences Working Group | Phase II (NYR) | NCT05013034 | IL-2 | AOR | FDA approved 12/5/98 | Chimeric IgG1κ |
| Foralumab | Tiziana Life Sciences, PLC | Phase II (NYR) | NCT04983446 | CD3ε | CD, MS | Phase II | Human IgG1κ |
|
Adakveo® (Crizanlizumab-tmca) |
Novartis | Phase II (C, NKFD) | NCT04435184 | PSGL-1 | SCDA-VOC | US-FDA approved 11/15/19 | Humanized IgG2κ |
|
Astegolimab (RG6149; AMG 282; MSTT1041A) |
Genentech | Phase II (C, D) | NCT04386616 | ST2 (IL-33R) | Atopic asthma | Phase II | Human IgG2κ |
|
Efmarodocokin alfa UTTR1147A |
Genentech | Phase II (C, D) | NCT04386616 | IL-22 | GVHD, NIH | Phase II | IL-22-IgG4-Fc fusion protein |
|
CD24Fc g (MK-7110) |
Merck (OncoImmune) | Phase III (C, D) | NCT04317040 | P-selectin | GVHD, ALL, AML, MDS | Phase II/III | CD24-Fc fusion protein |
|
Gamifant® (Emapalumab-lzsg) |
NovImmune/SOBI | Phase II/III (T, D) | NCT04324021 | IFN-γ | HLH | US-FDA approved 11/20/18 | Fully Human IgG1λ |
|
Pamrevlumab (FG-3019) |
Fibrogen | Phase II (T, NKFD) | NCT04432298 | CTGF | DMD, IPF | Phase III | Human IgG1κ |
| CPI-006 | Corvus |
Phase III (SUS) Phase I (C) |
CD73 | Solid tumors | Phase III | Humanized IgG1 |
AD Atopic dermatitis, aHUS atypical hemolytic uremic syndrome, ALS amyotrophic lateral sclerosis, AML adult acute myeloid leukemia, ANR clinical trial status as active but not recruiting, AS Ankylosing spondylitis, BI Boehringer Ingelheim, BMS Bristol-Myers Squibb, C completed, CaD Castleman’s disease, CAPS Cryopyrin-associated periodic syndrome, CCR5 C-C chemokine receptor type 5, CD cluster of differentiation, CrD Crohn’s disease, CMD Complement-mediated diseases, CMML chronic myelomonocytic leukemia, CRC colorectal cancer, CTGF connective tissue growth factor, D discontinued (typically based on press release from sponsor), DMD Duchenne Muscular Dystrophy, EC European Commission, EUA emergency use authorization, Fc IgG fragment (crystallizable), FTD fast track designation (by US-FDA), GB glioblastoma, GCA giant cell arteritis, GM-CSF granulocyte-macrophage colony-stimulating factor, GVHD graft-versus-host disease, HAE hereditary angioedema, HIV human immunodeficiency virus, HLE half-life extension, HLH hemophagocytic lympho-histiocytosis, HPV human papillomavirus, HSCT-TMA hematopoietic stem cell transplant-associated thrombotic microangiopathy, IFN interferon, IL interleukin, INFL inflammation/inflammatory disease, IPF idiopathic pulmonary fibrosis, JMML juvenile myelomonocytic leukemia, KTR kidney transplant rejection, LIGHT homologous to lymphotoxin exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator a receptor expressed on T lymphocytes, MASP-2 Mannan-binding lectin-associated serine protease-2, MCD Multicentric Castleman’s disease, MMel metastatic melanoma, MND motor neuron diseases, NA not applicable, NASH nonalcoholic steatohepatitis, NKFD no known future development plans, NKG2ACD94/NK (natural killer) group 2 member A, PML progressive multifocal leukoencephalopathy, PICC-ADVT peripherally inserted central venous catheter (PICC)-associated deep vein thrombosis (DVT), pKal plasma kallikrein, PNH paroxysmal nocturnal hemoglobinuria, PSGL-1 P-selectin glycoprotein ligand-1 (aka CD162), PsA psoriatic arthritis, PsO Psoriasis, R recruiting, RA rheumatoid arthritis, rh recombinant human, RYR clinical trial registered but not yet recruiting, SCDA-VOC sickle cell disease associated vaso-occlusive crises, SUS clinical trial suspended (sponsor decision), T terminated clinical trial, TNBC triple-negative breast cancer, TNF tumor necrosis factor, UK United Kingdom, US-FDA United States Food and Drug Administration, VEGF vascular endothelial growth factor, WHO World Health Organization
aNot all COVID-19-related trials are included here
bAtal et al. [520]
c[521]
dIn diabetic patients who contract COVID-19, after not meeting endpoints for treatment of COVID-19 directly
eUS-FDA stated on 5/17/21 that the data did not support clinical benefit for use of leronlimab to treat COVID-19
fGranted fast track designation by US-FDA on 11 May 2021 based on Phase 2 data, so further development expected
gIn Merck 10-k filing on 2/25/21, Merck stated that FDA requested additional studies to support an EUA filing, ultimately resulting in Merck discontinuing on development of MK-7110 for COVID-19