PowerPoint Presentation


Efgartigimod: Clinical Development of a Novel FcRn Antagonist in the Treatment of Autoimmune Diseases
Olga Ostrovskaya,1 Magdalena Sips,1 Peter Ulrichts,1 Lance Trainor,1 Peter Verheesen,1 Ivaylo Stoykov1
1argenx, Ghent, Belgium

• The neonatal Fc receptor, FcRn, recycles immunoglobulin G (IgG), extending its half-life and 
serum concentration1

• Efgartigimod is a human IgG1 Fc fragment, a natural ligand of FcRn, engineered for increased 
affinity for FcRn2

• Efgartigimod was designed to outcompete endogenous IgG, preventing recycling and promoting 
lysosomal degradation of IgG, without impacting its production2–5

o Targeted reduction of all IgG subtypes
o No impact on IgM or IgA
o No reduction in albumin levels
o No increase in cholesterol

1. Sesarman A, et al. Cell Mol Life Sci. 2010;67:2533–50. 2. Ulrichts P, et al. J Clin Invest. 2018;128:4372–86. 3. Vaccaro C, et al. Nat Biotech. 2005;23:1283–88. 4. Newland AC, et al. Am J Hematol. 2020;95:178–87. 5. Goebeler M, et al. Br J Dermatol. 2022;10:1111. 
6. Howard JF Jr, et al. Lancet Neurol. 2021;20:526–36. 7. argenx, Inc. (March 22, 2022). Topline Results: ADAPT-SC Bridging Study in gMG. 8. argenx, Inc. (May 5, 2022). Topline Results: ADVANCE study in ITP. 9. Schmidt E, et al. Lancet. 2019;394:882. 
10. Amagai M, et al. J Am Acad Dermatol. 1999;40:167–70. 11. Kridin K, et al. Front Med (Laussane). 2018;5:220. 

REFERENCES

OO, MS, PU, LT, PV, IS: Employees of argenx. 
Clinical trials mentioned above are funded by argenx. 

DISCLOSURES & ACKNOWLEDGMENTS

Pemphigus and Bullous Pemphigoid: IgG-Mediated Autoimmune Diseases9–11

• PV and PF belong to a heterogeneous group of autoimmune blistering diseases and are clinically characterized by mucosal erosions (PV) and cutaneous 
blisters (PV and PF)

• PV is characterized by the presence of pathogenic IgG autoantibodies targeting desmoglein 3 (Dsg-3), and 50% of the cases, also against desmoglein 1 
(Dsg-1)

• PF is attributed to the presence of IgG autoantibodies solely directed against Dsg-1
• Pemphigus is potentially life-threatening, primarily due to secondary infections
• Bullous pemphigoid (BP) is the most prevalent autoimmune blistering disease; it is characterized by subepidermal blisters and mediated by IgG 

autoantibodies directed against BP-230 and BP-180 antigens

IV, intravenous; SC, subcutaneous. 
Efgartigimod is co-formulated with hyaluronidase PH20 for convenient SC administration in <2 min. 
The investigational study drug, efgartigimod, has not been approved for use in PV/PF or BP by any regulatory agency as efficacy and safety have not been established.

Presented at the 2023 Winter Clinical Dermatology Conference; January 13–18, 2023; Kohala Coast, HI.

Efgartigimod: Engineered IgG1 Fc Fragment1–5

Program Indication Preclinical Phase 1 Phase 2 Phase 3

Efgartigimod

Generalized Myasthenia Gravis (SC)
Chronic Inflammatory Demyelinating Polyneuropathy (SC)
Idiopathic Inflammatory Myopathy/Myositis (SC)
Pemphigus Vulgaris and Foliaceus (SC)
Bullous Pemphigoid (SC)
Primary Immune Thrombocytopenia (IV)
Primary Immune Thrombocytopenia (SC)
Membranous Nephropathy
Lupus Nephritis 
Sjogren Syndrome
COVID-19 Mediated Postural Orthostatic Tachycardia Syndrome

ARGX-117
Multifocal Motor Neuropathy 
Delayed Graft Function After Kidney Transplantation

ARGX-119 Neuromuscular Indications
ARGX-120 Undisclosed
ARGX-118 Airway Inflammation (Non-Autoimmune Program)

Efgartigimod is approved for the treatment of gMG in patients positive for AChR antibodies in the US, as an add-on to standard 
therapy in patients positive for AChR antibodies in the EMEA, and in patients with and without AChR antibodies with insufficient

response to steroids or nonsteroid immunosuppressive therapies in Japan

Efgartigimod is also being evaluated in phase 3 trials in chronic inflammatory demyelinating polyneuropathy, idiopathic inflammatory myositis, pemphigus 
(PV and PF), BP, and primary ITP

Efgartigimod Reduces Total IgG Including Pathogenic IgG Autoantibody Levels4–7

• In a phase 2 study of participants with ITP, treatment with efgartigimod IV 10 mg/kg induced a reduction in serum levels of total IgG up to a mean change 
of 64% from baseline4

o In 70% of participants treated with efgartigimod IV 10 mg/kg, a reduction >40% in at least 1 type of platelet-associated autoantibody (GPIIb/IIIa, GPIb/IX, 
GPIa/IIa) signal was observed at days 25/29 and/or Day 784

• In a phase 2 study of participants with PV or PF, serum total IgG levels decreased by a median of 62% with efgartigimod IV 10 mg/kg and by a median of 
66% with efgartigimod IV 25 mg/kg5

o At the end of induction, serum levels of anti-Dsg-1 and anti-Dsg-3 IgG reached a median 61% reduction from baseline for anti-Dsg-1 and 49% for anti-
Dsg-3 antibodies5

• In a phase 3 study of participants with gMG positive for acetylcholine receptor (AChR) antibodies, a mean maximum reduction of total IgG by 61.3% was 
observed in participants treated with efgartigimod IV 10 mg/kg6

Mean percentage change from baseline in serum levels of total IgG in participants with gMG, primary ITP, and healthy volunteers treated with efgartigimod IV.4,6
gMG, generalized myasthenia gravis; HV, healthy volunteer; IgG, immunoglobulin G; ITP, immune thrombocytopenia; IV, intravenous; SE, standard error.

-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

0

10

0 1 2 3 4 5 6 7 8 9 10 11 12

Total IgG – HV vs Patients

Patients With gMG 
(ARGX-113-1602)

Patients With ITP 
(ARGX-113-1603)

Healthy Volunteers 
(ARGX-113-1702)

Patients With gMG 
(ARGX-113-1704)

M
ea

n 
(±

SE
) T

ot
al

 Ig
G

 C
ha

ng
e

Fr
om

 B
as

el
in

e 
(%

)

NEUROMUSCULAR HEMATOLOGY DERMATOLOGY NEPHROLOGY OTHER

Image adapted from Kang TH, Jung ST. Boosting therapeutic potency of 
antibodies by taming Fc domain functions. Exp Mol Med. 2019;51:1-9 and 
distributed under the terms of the Creative Commons CC-BY license 
(https://creativecommons.org/licenses/by/4.0/).

EFGARTIGIMOD IS CLINICALLY EFFECTIVE AND WELL TOLERATED IN PHASE 2 AND 3 TRIALS IN IgG-MEDIATED DISORDERS4–8

• Consistent depletion of total IgG levels of roughly 60% from baseline with efgartigimod intravenous (IV) treatment was observed across studies and 
populations

• In an open-label, phase 2 trial with efgartigimod IV in participants with pemphigus (pemphigus vulgaris [PV] and pemphigus foliaceus [PF]), disease 
control was achieved in 90% of participants (median time: 17 days) 

• Topline results of a phase 3, randomized, placebo-controlled study (ADVANCE IV) with efgartigimod IV in participants with primary immune 
thrombocytopenia (ITP) have also reported efficacy and safety in this patient population - the primary endpoint, platelet-related key secondary 
endpoints, and International Working Group response criteria were met; no new safety signals were observed

• In a phase 3 trial in participants with generalized myasthenia gravis (gMG), 68% of participants responded to efgartigimod IV (MG-ADL responders*) 
compared with 30% of those in the placebo group
o In a study comparing efgartigimod administered intravenously or subcutaneously in participants with gMG, consistent clinical efficacy and safety 

were observed in both groups (MG-ADL responders: 69.1% IV vs 69.1% subcutaneous [SC]; n=110)

• Efgartigimod treatment was generally well tolerated in phase 2 and 3 trials in participants with pemphigus (open-label study), primary ITP, and gMG
o Most common adverse events in treatment and placebo groups across studies to date include headache, nausea, nasopharyngitis, diarrhea, 

abdominal pain, upper respiratory tract infection, and urinary tract infection

*MG-ADL responders = ≥2-point Myasthenia Gravis Activities of Daily Living score improvement sustained for ≥4 weeks. 

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