Evolving Treatment Approaches for

Generalized Myasthenia Gravis to

Reduce Disease Burden and
Improve Daily Living
Presented by:

James F. Howard, Jr., M.D.

Professor of Neurology, Medicine & Allied Health
Departments of Neurology, Medicine & Allied Health
The University of North Carolina at Chapel Hill
Professor of Clinical Sciences (Neurology)
Department of Clinical Sciences (Neurology)
North Carolina State College of Veterinary Medicine

Jeffrey T. Guptill MD, MA, MHS

Associate Professor of Neurology
Duke University School of Medicine
Durham, NC

This activity is supported by an educational grant from argenx.

Faculty Disclosures

▪ James F. Howard, Jr., M.D

− Contracted Research: Alexion Pharmaceuticals, argenx BVBA, the Centers for
Disease Control and Prevention (Atlanta, GA, USA), the Myasthenia Gravis Foundation
of America, the Muscular Dystrophy Association, the National Institutes of Health
(including the National Institute of Neurological Disorders and Stroke and the National
Institute of Arthritis and Musculoskeletal and Skin Diseases), PCORI, Ra
Pharmaceuticals (now UCB), Regeneron Pharmaceuticals and Takeda Pharmaceuticals;
Honoraria from Alexion Pharmaceuticals, argenx BVBA, Immunovant Inc., Ra
Pharmaceuticals (now UCB), Regeneron Pharmaceuticals, Sanofi US and Viela Bio Inc.
(now Horizon Therapeutics)

− Non-financial support: Alexion Pharmaceuticals, argenx BVBA, Ra Pharmaceuticals

(now UCB) and Toleranzia AB

▪ Jeffrey T. Guptill MD, MA, MHS

− Consulting Fees (e.g., advisory boards): Alexion, Apellis, Argenx, Becton Dickinson,
Cabaletta, Grifols, Immunovant, Jacobus Pharmaceuticals, Janssen, Momenta,
Piedmont Pharmaceuticals, Ra Pharma, Regeneron, Toleranzia, and UCB

− Contracted Research: Argenx, Centers for Disease Control and Prevention, Janssen,
Myasthenia Gravis Foundation of America, NIH (NIAID, NINDS, NIMH), Takeda, and
UCB Pharma

2
 Learning Objectives

▪ Describe the impact of comorbidities on the burden of disease, QoL,

and selection of personalized treatment for patients with gMG

▪ Define the profiles of patients who could benefit from emerging

targeted treatment options for gMG based on the results of antibody
testing, limitations of currently available treatment options, and
comorbidities

▪ Summarize the mechanism of action, efficacy, safety, and place in

therapy of new and emerging targeted treatment options for gMG

▪ Explain how current management of gMG with available treatments

drives up healthcare costs and negatively impacts patients’ QoL

3
 Medications Discussed in this
Presentation
Eculizumab was FDA-approved in October 2017 to treat
generalized myasthenia gravis.

NOTE: On
Efgartigimod, Decemberinebilizumab,
batoclimab, 17, 2021 (after this program was
nipocalimab,
recorded),
ravulizumab, the FDA approved
rozanolixizumab, efgartigimod
and zilucoplan arefor the
investigational
drugs treatment
for MG. Note that at the time
of generalized of this broadcast
myasthenia andin
gravis (gMG)
recording, efgartigimod
adults is under
who test positive forFDA
the review for treatment of
anti-acetylcholine
gMG, receptor
with an imminent target action date of December 17, 2021.
(AChR) antibody.

Other drugs mentioned, while FDA-approved for other uses, are

used off label in MG.
4
5
6
Burden of Disease & Treatment
The advent of targeted novel therapeutics will force
us to consider the broad concepts of disease and
treatment burden in our management decisions
8
 Burden of Disease

100
100 0%
1920
Tracheostomy/
endotracheal intubation 1929 Negative-pressure ventilation
Patients with gMG in remission or

Patients, %
75
75 Neostigmine 1934
1935
whose symptoms improved2 25%
Sulfonamides (from 1940 onward; estimated)
Mortality, %

Antibiotics 1935-1946
1939
Thymectomy 50%
50
50
ACTH and steroids
Azathioprine
Mortality in MG 1-3 1957 Cyclophosphamide
Cyclosporine Patients
25
25 1966 1970-1980s 75% with
Positive-pressure ventilation
1970 unmet
IVIg
Methotrexate 1975 Mycophenolate mofetil need2,4,a
Eculizumab
1984
PLEX 1998 100%
2017
00
1900s 1910s 1920s 1930s 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s

ACTH, adrenocorticotropic hormone; PLEX, plasma exchange.

aPatients with gMG whose symptoms remained unchanged or worsened, or patients who died.2 Figure adapted from Grob D, et al.6
1. Mantegazza R and Antozzi C. et al Ther Adv Neurol Disord. 2018;11:1756285617749134.
2. Grob D et al. Muscle Nerve. 2008;37(2):141-149.
3. Keesey JC. et alSemin Neurol. 2004;24(1):5-16.
4. Sanders DB and Evoli A. et al Autoimmunity. 2010;43(5-6):428-435.
5. Suh J et al. Yale J Biol Med. 2013;86(2):255-260. 9
6. Buzzard KA et al. Muscle Nerve. 2015;52(2):204-210.
10
 Myasthenia Gravis
Disease Burdena
50% have moderate to severe
symptoms (MG-ADL > 6)
Mean MG-QOL15: 22.2

Mean MG-ADL: 6.2

Mean disease duration:
Percent

Percent
9.9 yrs

worsening symptoms worsening quality of life

MG-ADL = myasthenia gravis activities of daily living.

aBased on a cross-sectional analysis of participants in the MGFA Patient Registry participants.
bMeasure of symptom severity (ocular, oropharyngeal, respiratory, and extremity function).
11
Cutter G, et al. Muscle Nerve. 2019;60:707-715. N = 1140 Patients in the MGFA Patient Registry
Treatment Efficacy is Lacking for Many
gMG Patients

MGFA = Myasthenia Gravis Foundation of America; gMG = generalized myasthenia gravis. 12

Cutter G, et al. Muscle Nerve. 2019;60(6):707-715 N = 1140 Patients in the MGFA Patient Registry
Myasthenia Gravis
Disease Burden
Burden of disease Potentially modified by
may include individual patient
characteristics, e.g.3
• Impaired activities of daily living1 • Comorbidities2
• Risk of hospitalization or • Management and related AEs4
exacerbations1,2 • Age4
• Impaired health-related quality • Employment status3
of life1
• Sex4
• Lack of treatment response
• Antibody status4

AE, adverse event; gMG = generalized myasthenia gravis.

1. Howard JF Jr et al. Lancet Neurol. 2017;16(12):976-986.

2. Engel-Nitz N et al. Muscle Nerve. 2018;58:99-105.
3. Barnett C et al. PLoS One. 2014;9(5):e98089. 13
4. Suh J et al. Yale J Biol Med. 2013;86:255-260.
Patient Vignette: Disease Burden
 Myasthenia Gravis
Treatment Burden
Patient dissatisfaction
with treatments
is related to

Side Effects
Prolonged Time to Difficult /
≥33% in all Lack of Efficacy1 Inconvenient
Onset of Effect1
treatment 8%–41% Administration1
groups1 19%–42%b
>33%c
>80% report
prednisone AEs2,a
Based on surveys of patients in the Myasthenia Gravis Patient Registry
N =3721 and N =2982
aIncludes only those survey respondents who had ever taken prednisone. bFor all types of MG treatments except PLEX. cIncludes patients treated with rituximab,
IVIg, PLEX, and/or current complement inhibitors.
AE, adverse PLEX, plasma exchange.
1. Mindspot Research. Myasthenia Gravis Patient Needs Exploration (2018). 15
2. Lee I, et al. Neurol Neuroimmunol Neuroinflamm. 2018;5(6):e507.
 Impact of Disease and Treatment
Burden on Employment

Germany2 Denmark4
N=1518 N=330

United States1 47% face long-

N=825 28% forced to retire term sickness
Work absenteeism early (average age of absence4
frequently reported, population: 56.7 years)
regardless of disease
status*,1
Australia6,7
Japan3 Thailand5 59% unable to work
N=680 N=71 due to the effects of
27% experienced Up to 58% their disease
unemployment unemployment (N=165;6 N=1907)
rate Those in employment
36% experienced Up to 48% face a reported a drop of almost
decreases in decrease in income 5 work hours per week after
income MG symptoms appeared
Results from surveys1–3,7 and an observational study6 of patients with MG. *Ranging from 1–3 days to over 1 month within the last 6 months in a survey of patients with gMG (N=825).
1. Harris L, et al. Muscle Nerve 2019;60:700–706; 2. Twork S, et al. Health Qual Life Outcomes 2010;8:129; 3. Nagane Y, et al. BMJ Open 2017;7:e013278; 4. Frost A, et al. BMC Neurol 2016;16:224; 5.
Kulkantrakorn K, et al. Neurol Sci 2010;31:571-73; 6. Blum S, et al. J Clin Neurosci 2015;22:1164–69; 7. Centre for International Economics. The Cost to Patients and the Community of Myasthenia Gravis.
Available at: https://www.touchneurology.com/wp-content/uploads/sites/3/2018/06/www.thecie.com_.au_wp-content_uploads_2014_06_Final-report_Economic-Impact-of-Myasthenia-Gravis- 16
08112013.pdf (Accessed November 2021).
Used with permission of Michelle Mackechnie, PhD.
 Myasthenia Gravis
Treatment Burden
Many treatments have tolerability and inconvenience limitations1,2
AChEI2 Steroids2 ISTs1,3 IVIg/PLEX1,2,4 Rituximab1,2 Eculizumab5-7
Nausea, diarrhea, Skin atrophy, Bone marrow Allergic reactions, Infusion-related Treatment
abdominal glaucoma, mood suppression, risk of infection, headache, nausea, resistance, biweekly
cramping, increased disorders, risk of leukopenia, hypotension, high chills, hypotension, infusions, cost,
salivation infection hypertension, GI cost, requires long anemia, leukopenia, cannot be used with
intolerance, infusion times and thrombocytopenia FcRn inhibitors
infection special treatment

Some carry an added risk of systemic toxicity with chronic use1,2

N/A Weight gain, Long-term Nephrotoxicity, Progressive Meningococcal
osteoporosis, hepatotoxicity and thrombosis multifocal infections
diabetes nephrotoxicity, encephalopathy
malignancy

Many patients experience a latency period between treatment initiation and therapeutic onset1,2

AChEI = acetylcholinesterase inhibitor; IST = immunosuppressive treatment.

1. Farmakidis C et al. Neurol Clin. 2018;36:311-337.
2. Gilhus NE. N Engl J Med. 2016;375:2570-2581.
3. Gilhus NE et al. Nat Rev Dis Primers. 2019;5:30.
4. Heatwole C et al. J Clin Neuromuscul Dis. 2011;13:85-94.
5. SOLIRIS. Prescribing information. Alexion Pharmaceuticals Inc.; 2018.
6. Dhillon S. Drugs. 2018;78:367-376.
17
7. Nishimura J et al. N Engl J Med. 2014;370:632-639.
18
 Burdens of gMG

Treatment and non-treatment–refractory gMG patients

also have increased health care costs

Schneider-Gold C, et al. Ther Adv Neurol Disord. 2019;12:1756286419832242. 19

 Myasthenia Gravis
Goals for New Treatments
▪ There is a rationale for improved therapy to address
both treatment and disease burden
▪ Goals of such therapy must include
− Achieve minimal manifestations (MM) or minimal
symptom expression (MSE)
− Reduce the treatment burdens of cumulative adverse
events and onerous treatment logistics
− Be directed at the pathogenic basis of the disease
▪ Now recognized that multiple mechanisms impair
synaptic transmission
Dalakas MC. Nat Rev Neurol 2019;15:113-124.
Sanders DB, et al. Neurology. 2016;87(4):419-425. 20
Thomsen JLS, et al. Front Neurol. 2020;11:596382.
Current and Future Treatments
for Myasthenia Gravis
Patient Vignette:
Treatment/Burden of Disease
Overview

▪ Current treatment options

▪ Putting it all together
− Basic approach
− Pitfalls
▪ The future

23
 Burden of Disease

100
100 0%
1920
Tracheostomy/
endotracheal intubation 1929 Negative-pressure ventilation
Patients with gMG in remission or
whose symptoms improved2

Patients, %
75 Neostigmine 1934
75 1935 25%
Sulfonamides (from 1940 onward; estimated)
Mortality, %

Antibiotics 1935-1946
1939
Thymectomy 50%
50
50
ACTH and steroids
Azathioprine
Mortality in MG 1-3 1957 Cyclophosphamide
Cyclosporine Patients
25
25 1966 1970-1980s 75% with
Positive-pressure ventilation
1970 unmet
IVIg
Methotrexate 1975 Mycophenolate mofetil need2,4,a
Eculizumab
1984
PLEX 1998
00 2017 100%
1900s 1910s 1920s 1930s 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s

ACTH, adrenocorticotropic hormone; PLEX, plasma exchange.

aPatients with gMG whose symptoms remained unchanged or worsened, or patients who died.2 Figure adapted from Grob D, et al.6
1. Mantegazza R and Antozzi C. Ther Adv Neurol Disord. 2018;11:1756285617749134.
2. Grob D et al. Muscle Nerve. 2008;37(2):141-149.
3. Keesey JC. Semin Neurol. 2004;24(1):5-16.
4. Sanders DB and Evoli A. Autoimmunity. 2010;43(5-6):428-435.
5. Suh J et al. Yale J Biol Med. 2013;86(2):255-260. 24
6. Buzzard KA et al. Muscle Nerve. 2015;52(2):204-210.
 Current Treatment Options

Symptomatic Immunomodulatory Immunosuppressive Thymectomy

IVIg Corticosteroids
Pyridostigmine

Azathioprine
Therapeutic
Plasma
Exchange Mycophenolate
mofetil

Eculizumab Tacrolimus

Cyclosporine
Rituximab

Methotrexate

Cyclophosphamide

25
26
 Putting It All Together: Basic
Therapeutic Approach
▪ Start with pyridostigmine in nearly all patients
▪ CT of the chest to evaluate for thymoma
▪ Thymectomy in patients who are anti-AChR+ and patients with thymoma
▪ If inadequate response to AChE inhibitor, start steroids in most patients
− 20 mg/d for ocular MG, 60 mg/d for generalized MG
− Achieve maximal improvement, then taper

▪ Consider steroid-sparing drugs for long term treatment or when steroids

are contraindicated
▪ TPE or IVIg for severe disease, exacerbations, or crisis
▪ Eculizumab for patients with severe, refractory anti-AChR+ MG (per
guidance, but FDA-approved for refractory anti-AChR+ MG)
▪ Consider early rituximab for patients with MuSK+ MG
MuSK = muscle-specific tyrosine kinase.
27
Narayanaswami P et al. Neurology. 2021;96(3):114-122.
Saunders DB et al. Neurology. 2016 Jul 26;87(4):419-25.
Consensus Guidelines Provide
Additional Information

28
 Real-world Data For MG Treatments

2011 (N = 1,288)1 2021 (N = 1,156)2

ACheI 80% 67%
Corticosteroids 50% 38%
Azathioprine 17% 15%
Mycophenolate mofetil 13% 29%
Rituximab - 6%
IVIg 12% 22%
Eculizumab - 7%

1. Guptill JT et al. Muscle Nerve. 2011;44(6):907-911. (Claims data)

2. Unpublished data, survey of patients through MGFA.
29
Most Common Treatment Pitfalls

▪ Not treating long enough

▪ Dose is too low

▪ Expectations are not laid out appropriately

▪ No objective measure followed to determine

if treatment is working
30
The Future
Limitations of Current Immunotherapies

▪ Nonselective
− Widespread suppression of immune system
function
▪ Delayed response
▪ Cost
▪ Limited data
▪ Persistent patient burden – disease and
treatments (e.g., daily therapy, monitoring)
32
Limitations of Current Immunotherapies

Prednisone ▪ Azathioprine
▪ Weight gain − Idiosyncratic flu-like illness
▪ Glucose intolerance • 10-15%
▪ Bone loss − Toxic hepatitis
▪ Edema − Bone marrow suppression
▪ Hypertension − Idiosyncratic pancreatitis
▪ Insomnia − Long-term cancer risk
▪ Behavior − Teratogen
▪ Cosmesis ▪ Mycophenolate mofetil
− Cushingoid facies − Bone marrow suppression
− Skin changes − GI upset (27%)
▪ Gastritis − Long-term cancer risk
− Teratogen
Infections

33
Autoantibody-mediated Attack on the
Acetylcholine Receptor

Differentiation Plasma
B cell
cell
AChR Antibody

Acetylcholine
Receptor

Complement,
Membrane
B cell/Plasma Cell Therapies
attack
complex
FcRn Inhibitor
Therapies

Complement
Inhibitor
Therapies
Muscle Cell

34
Adapted from Guptill JT et al., Neurotherapeutics. 2016;13(1):118-131.
B cell/Plasma Cell Therapies
Autoantibody-mediated Attack on the
Acetylcholine Receptor

B cell Differentiation Plasma

cell
AChR Antibody

Acetylcholine Receptor

Complement,
Membrane
B cell/Plasma Cell Therapies
Attack
Complex
FcRn Inhibitor
Therapies

Complement
Inhibitor
Therapies Muscle Cell

36
Adapted from Guptill JT et al., Neurotherapeutics. 2016;13(1):118-131.
 Overview of B- and Plasma-cell–targeted
Treatments in Development for MG

Therapeutic Molecule Summary Status of Clinical Trials

Name
Mezagitamab Human IgG1 • Completed phase 1 trial in healthy volunteers
(TAK-079) monoclonal Ab • Completed phase 1 trial in relapsed/refractory
(anti-CD38) multiple myeloma
• Active phase 2 trial in MG

Inebilizumab Humanized IgG1 • Approved for NMOSD in adult AQP4-Ab+

(anti-CD19) monoclonal Ab patients
• Completed phase 1 trial in multiple sclerosis
• Completed phase 1 trial in systemic sclerosis
• Active phase 3 trial in MG

AQP4 = anti-aquaporin-4; NMOSD = neuromyelitis optica spectrum disorder.

Smithson G et al. J Immunol. 2017;198 (1 Supplement) 224.20.

Krishnan AY et al. J Clin Oncol. 2021;38 (15 suppl) 8539.
Fedyk ER et al. Br J Clin Pharmacol. 2020;86(7):1314-1325. 37
Cree BAC et al. Lancet. 2019;394(10206):1352-1363.
B-cell Surface Marker Expression

Antigen Independent Antigen Dependent

Noto D and Miyaki S. et al Clin Exp Neuroimmunol. 2020;11:163-170. 38

FcRn inhibition
Autoantibody-mediated Attack on the
Acetylcholine Receptor

B cell Differentiation Plasma

cell
AChR antibody

Acetylcholine receptor

Complement,
membrane
B cell/Plasma Cell Therapies
attack
complex
FcRn Inhibitor
Therapies

Complement
Inhibitor
Therapies Muscle Cell

Adapted from Guptill JT et al., Neurotherapeutics. 2016;13(1):118-131. 40

 FcRn-mediated Endosomal IgG Recycling
IgG
Bloodstream

Lysosomal degradation

Uptake

Recycling endosome

Acidified
endosome

Sorting FcRn –IgG complexes

IgG is recycled to blood

Gable K and Guptill J. et al Front Immunol. 2020;10:3052. 41

 Effect of FcRn Blocking on FcRn-mediated
IgG
Endosomal IgG Recycling
Bloodstream
Cell membrane

Uptake in Lysosomal degradation

endosome

Recycling endosome

Acidified
endosome
with FcRn
blocking

Sorting FcRn –antibody complexes

Gable K and Guptill J. et al Front Immunol. 2020;10:3052. 42

 Overview of FcRn-targeted Treatments
in Development for MG
Therapeutic Name Molecule Summary Status of Clinical Trials
Efgartigimod (ARGX- Humanized IgG1 Fc • Completed phase 1 trial in healthy volunteers
113) fragment • Completed phase 2 trial in MG
• Completed phase 3 trial in MG*
Nipocalimab (M281) Human deglycosylated • Completed phase 1 trial in healthy volunteers
IgG1 mAb • Completed phase 2 trial in MG
• Active phase 3 trial in MG
Rozanolixizumab Humanized IgG4 mAb • Completed phase 1 trial in healthy volunteers
(UCB7665) • Completed phase 2 trial in MG
• Active phase 3 trial in MG
Batoclimab Human IgG1 mAb • Completed phase 1 trial in healthy volunteers
(IMVT-1401, RVT- • Completed phase 2 trial in MG
1401, HL161)

*Efgartigimod is under FDA review for the treatment of gMG, with target action date of December 17, 2021. 43
Efgartigimod
 ▪ Parallel design with 1:1 randomization
(10mg/kg efgartigimod or PBO) for 26
weeks
▪ 4 infusions per cycle (one infusion per
week), repeated as needed depending
on clinical response, no sooner than 8
weeks after initiation of the previous
cycle
▪ Enrolled MuSK Ab+ and seronegative
MG
▪ MG-ADL score ≥5 (>50% non-ocular)
▪ Primary Outcome: MG-ADL
responders (≥2-point improvement for at
least four consecutive weeks) in AChR-
Ab+ patients in cycle 1 (8 weeks)

45
Howard JF, et al. Lancet Neurol. 2021;20(7):526-536.
Efgartigimod Phase 3 Results (ADAPT)
MG-ADL Score QMG Score

46
QMG = Quantitative Myasthenia Gravis.
Howard JF, et al. Lancet Neurol. 2021;20(7):526-536.
 Efgartigimod Phase 3 Results (ADAPT)

Efgartigimod PBO OR P value

(95% CI)
MG-ADL responder cycle 1 68% 30% 4.95 <0.0001
(primary) (2.21-11.53)

QMG responder cycle 1 63% 14% 10.84 <0.0001

(4.18-31.20)

MG-ADL responder cycle 1 68% 37% 3.70 <0.0001

(all) (1.85-7.58)

Early ADL responder cycle 1* 57% 25% N/A N/A

*ADL improvement of ≥2 by week 2.

47
Howard JF, et al. Lancet Neurol. 2021;20(7):526-536.
 Efgartigimod Phase 3 Safety (ADAPT)

48
Howard JF Jr et al. Lancet Neurol. 2021;20(7):526-536.
Complement Inhibition
Autoantibody-mediated Attack on the AChR

B cell Differentiation Plasma

cell
AChR Antibody

Acetylcholine Receptor

Complement,
membrane
B cell/Plasma Cell Therapies attack
complex
FcRn Inhibitor
Therapies

Complement
inhibitor
Therapies

Muscle Cell
Adapted from Guptill JT et al., Neurotherapeutics. 2016;13(1):118-131. 50
 MG Treatment: Eculizumab

0 4 8 12 16 20 24 0 4 8 12 16 20 24
week week

Effective for the treatment of refractory generalized MG with AChR antibodies

Howard JF Jr et al. Lancet Neurol. 2017;16(12):976-986.

51
 REGAIN Trial & Extension
Exacerbations and Hospitalization Rates
Exacerbation Rates MG-related Hospitalization Rates

Jacob S, et al. J Neuromusc Dis. 2018;5:S334. Presented at the 2018 Annual Meeting of the AANEM, Washington, DC, 2018. 52
 Overview of Complement-targeted Treatments
Available and in Development for MG

Therapeutic Name Molecule Summary Status of Clinical Trials

Eculizumab Humanized monoclonal Ab Approved for treatment of AChR

Targets C5 Ab+ generalized MG
IV administration every 2 wks Active phase 3 trial in pediatric MG

Ravulizumab Humanized monoclonal Ab Approved for treatment of PNH,

Targets C5 aHUS
IV administration every 8 wks Active phase 3 trial in MG
Zilucoplan Macrocyclic peptide Completed phase 1 trial in healthy
Targets C5 volunteers
SC administration daily Completed phase 2 trial in MG
Active phase 3 trial in MG
Zilucoplan XR Macrocyclic peptide Preclinical
Targets C5
SC administration weekly

* Other complement inhibitor-targeted therapeutics are in development.

53
Future Use of Novel Therapeutics in
MG
▪ Patients not responsive to existing
therapies
▪ Bridging therapy
▪ Patients experiencing
exacerbations
▪ Hospitalized patients
▪ Targeted combination treatment?
− Complement inhibition
− Autoantibody reduction Muscle Cell

54
 Burden of Disease
100
100 0%
1920
Tracheostomy/ 1929
endotracheal intubation
Patients with gMG in remission
75
75 Negative-pressure or whose symptoms improved2 25%
ventilation 1934 1935
(from 1940 onward; estimated)

Patients, %
Mortality, %

Neostigmin 1935-
e
Sulfonamides 1946
Antibiotics 1939
50
50 50%
Thymectomy
ACTH and steroids
Azathioprine
Mortality in MG 1-3 1957 Cyclophosphamide
Cyclosporine Several Patients
25
25 75%
new with
Positive-pressure ventilation 1966 1970 1970-1980s unmet
therapies
IVIg need2,4,a
Methotrexate 1975 Mycophenolate mofetil expected
Eculizumab
over next
1984
PLEX 1998 5 years
00 2017 100%
1900s 1910s 1920s 1930s 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s

Figure adapted from Grob D, et al. Muscle Nerve. 2008;37:141-149.

ACTH, adrenocorticotropic hormone; IVIg, intravenous immunoglobulin; PLEX, plasma exchange.
aPatients with gMG whose symptoms remained unchanged or worsened, or patients who died.2

1. Mantegazza R, Antozzi C. Ther Adv Neurol Disord. 2018;11:1756285617749134. 2. Grob D, et al. Muscle Nerve. 2008;37:141-149. 3. Keesey JC. Semin 55
Neurol. 2004;24(1):5-16. 4. Sanders DB, Evoli A. Autoimmunity. 2010;43(5-6):428-435. 5. Suh J, et al. Yale J Biol Med. 2013;86:255-260. 6. Buzzard KA, et
al. Muscle Nerve. 2015;52:204-210.
Conclusions

▪ Disease burden is clear and easier to measure

▪ Treatment burden needs to be taken into account,
particularly with new targeted therapies
▪ Therapies targeting multiple mechanisms of disease
are in development that should provide additional
effective treatment options and lessen treatment
burden
▪ We need to get smarter about how to select the best
therapy for a given patient (biomarkers)
▪ Real-world evidence will give us additional
information on optimal patient choice, dosing, and
combination therapy, and long-term side effect
profiles
56
Q&A
Live Q&A with the experts

57
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Against Miami, Florida U.S.A
Myasthenia Gravis
Registration and full program will be posted on
myasthenia.org

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