Study design

Learn more about how the pivotal clinical trial for VYVGART was set up to include a range of patients.

The ADAPT phase 3 clinical trial study design1,2

A 26-week, multicenter, randomized, double-blind, placebo-controlled trial in 167 adult patients with gMG

Adapt study design

The majority of patients (n=65 for VYVGART; n=64 for placebo) were positive for AChR antibodies*

*All patients received stable doses of their current gMG treatment.

†All patients received an initial cycle, with subsequent cycles administered based on individual clinical evaluation when their MG-ADL score was at least 5 (with >50% MG-ADL nonocular) and if the patient was an MG-ADL responder, when they no longer had a clinically meaningful decrease (defined as having ≥2-point improvement in total MG-ADL score) compared to baseline. The minimum time between treatment cycles, specified by study protocol, was 50 days. A maximum of 3 cycles were possible in the 26-week study.

‡The percentage of anti-AChR antibody positive patients who were MG-ADL responders, defined as a ≥2-point reduction in the total MG-ADL score compared to the treatment cycle baseline for at least 4 consecutive weeks during the first treatment cycle (by week 8), with the first reduction occurring no later than 1 week after the last infusion of the cycle.

AChR=acetylcholine receptor; gMG=generalized myasthenia gravis; MG-ADL=Myasthenia Gravis Activities of Daily Living; Tx=treatment.

BASELINE PATIENT DEMOGRAPHICS

The pivotal trial population represented a range of adult patients with gMG1-3

MGFA class at screening

Class II (Mild): 40%

Class III (Moderate): 56%

Class IV (Severe): 4%

167

patients

Mean age: 46

Female: 75%

Anti-AChR antibody
positive: n=65/84

9

mean baseline
(MG-ADL score; both arms)*

MG-ADL 5-7: 24%

MG-ADL 8-9: 37%

MG-ADL ≥10: 39%

(0=normal; 24=most severe)

16

mean baseline
(QMG score; both arms)*

Range: 4-28 (overall)

(0=normal; 39=most severe)

MGFA class at screening

Class II (Mild): 37%

Class III (Moderate): 59%

Class IV (Severe): 4%

167

patients

Mean age: 48

Female: 66%

Anti-AChR antibody
positive: n=64/83

9

mean baseline
(MG-ADL score; both arms)*

MG-ADL 5-7: 27%†

MG-ADL 8-9: 41%†

MG-ADL ≧10: 33%†

(0=normal; 24=most severe)

16

mean baseline
(QMG score; both arms)*

Range: 4-28 (overall)

(0=normal; 39=most severe)

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Patients should be advised to complete age-appropriate vaccinations according to immunization guidelines prior to initiation of a new treatment cycle with VYVGART. Vaccination with live-attenuated or live vaccines is not recommended during treatment with VYVGART. No specific vaccinations were required in the ADAPT clinical trial inclusion criteria.

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gMG treatments at study entry (in each arm): NSISTs (~60%), steroids (>70%), acetylcholinesterase inhibitors (>80%).

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5 most prevalent comorbidities identified at baseline (overall population)‡: hypertension (28%), depression (13%), diabetes mellitus (10%), osteoporosis (9%), gastroesophageal reflux disease (9%).

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Patients who had active hepatitis B, were seropositive for hepatitis C, were seropositive for HIV with low CD4 count, had severe infections, or had evidence of any significant serious malignant disease were not eligible to participate in the ADAPT trial.

*MG-ADL total score of ≥5 required at screening.

†Sum of the percentages is over 100% due to rounding.

‡Conditions shown represent the 5 most prevalent comorbidities reported by investigator at baseline in the ADAPT clinical trial (N=167).

AChR=acetylcholine antibody receptor; MG-ADL=Myasthenia Gravis Activities of Daily Living; MGFA=Myasthenia Gravis Foundation of America; NSIST=nonsteroidal immunosuppressive therapy; QMG=Quantitative Myasthenia Gravis.

Infection

VYVGART may increase the risk of infection. The most common infections observed in Study 1 were urinary tract infection (10% for VYVGART vs 5% for placebo) and respiratory tract infection (33% for VYVGART vs 29% for placebo). Patients on VYVGART vs placebo had below normal levels for white blood cell counts (12% vs 5%, respectively), lymphocyte counts (28% vs 19%, respectively), and neutrophil counts (13% vs 6%, respectively). The majority of infections and hematologic abnormalities were mild to moderate in severity. Delay VYVGART administration in patients with an active infection until the infection is resolved; monitor for clinical signs and symptoms of infections. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART until the infection has resolved.

Immunization

Immunization with vaccines during VYVGART treatment has not been studied; the safety with live or live-attenuated vaccines and the response to immunization with any vaccine are unknown. Because VYVGART causes a reduction in immunoglobulin G (IgG) levels, vaccination with live-attenuated or live vaccines is not recommended during VYVGART treatment. Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART.

Hypersensitivity Reactions

Hypersensitivity reactions, including rash, angioedema, and dyspnea, were observed with VYVGART. In clinical trials, hypersensitivity reactions were mild or moderate, occurred within 1 hour to 3 weeks of administration, and did not lead to treatment discontinuation. Monitor patients during administration and for 1 hour thereafter for clinical signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs during administration, discontinue VYVGART infusion and institute appropriate supportive measures if needed.

ADVERSE REACTIONS

The most common (≥10%) adverse reactions with VYVGART were respiratory tract infection, headache, and urinary tract infection.

USE IN SPECIFIC POPULATIONS

Pregnancy

As VYVGART is expected to reduce maternal IgG antibody levels, reduction in passive protection to the newborn is anticipated. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to VYVGART in utero.

Lactation

There is no information regarding the presence of VYVGART in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VYVGART and any potential adverse effects on the breastfed infant from VYVGART or from the underlying maternal condition.

INDICATION

VYVGART® (efgartigimod alfa-fcab) is indicated for the treatment of generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Please see the full Prescribing Information.

You may report side effects to the US Food and Drug Administration by visiting http://www.fda.gov/medwatch or calling 1-800-FDA-1088. You may also report side effects to argenx US, Inc, at 1-833-argx411 (1-833-274-9411).

Infection

VYVGART may increase the risk of infection. The most common infections observed in Study 1 were urinary tract infection (10% for VYVGART vs 5% for placebo) and respiratory tract infection (33% for VYVGART vs 29% for placebo). Patients on VYVGART vs placebo had below normal levels for white blood cell counts (12% vs 5%, respectively), lymphocyte counts (28% vs 19%, respectively), and neutrophil counts (13% vs 6%, respectively). The majority of infections and hematologic abnormalities were mild to moderate in severity. Delay VYVGART administration in patients with an active infection until the infection is resolved; monitor for clinical signs and symptoms of infections. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART until the infection has resolved.

Immunization

Immunization with vaccines during VYVGART treatment has not been studied; the safety with live or live-attenuated vaccines and the response to immunization with any vaccine are unknown. Because VYVGART causes a reduction in immunoglobulin G (IgG) levels, vaccination with live-attenuated or live vaccines is not recommended during VYVGART treatment. Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART.

Hypersensitivity Reactions

Hypersensitivity reactions, including rash, angioedema, and dyspnea, were observed with VYVGART. In clinical trials, hypersensitivity reactions were mild or moderate, occurred within 1 hour to 3 weeks of administration, and did not lead to treatment discontinuation. Monitor patients during administration and for 1 hour thereafter for clinical signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs during administration, discontinue VYVGART infusion and institute appropriate supportive measures if needed.

ADVERSE REACTIONS

The most common (≥10%) adverse reactions with VYVGART were respiratory tract infection, headache, and urinary tract infection.

USE IN SPECIFIC POPULATIONS

Pregnancy

As VYVGART is expected to reduce maternal IgG antibody levels, reduction in passive protection to the newborn is anticipated. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to VYVGART in utero.

Lactation

There is no information regarding the presence of VYVGART in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VYVGART and any potential adverse effects on the breastfed infant from VYVGART or from the underlying maternal condition.

INDICATION

VYVGART® (efgartigimod alfa-fcab) is indicated for the treatment of generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Please see the full Prescribing Information.

You may report side effects to the US Food and Drug Administration by visiting http://www.fda.gov/medwatch or calling 1-800-FDA-1088. You may also report side effects to argenx US, Inc, at 1-833-argx411 (1-833-274-9411).

References: 1. VYVGART. Prescribing information. argenx US Inc; 2022. 2. Howard JF Jr et al. Lancet Neurol. 2021;20(7):526-536. doi:10.1016/S1474-4422(21)00159-9 3. Data on file, argenx US Inc. December 2022.