Last updated Sept. 22, 2022, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD
What is Vyvgart for Myasthenia Gravis?
Vyvgart (efgartigimod) is an approved treatment for generalized myasthenia gravis (gMG) developed by Argenx. It’s designed to lower the number of circulating self-reactive antibodies that wrongly attack healthy tissues in gMG.
Formerly known as ARGX-113, Vyvgart has been awarded orphan drug status in both the U.S. and Europe.
How does Vyvgart work?
Antibodies, or immunoglobulins, are proteins produced by the immune system in response to foreign molecules invading the body. They fall into five classes: IgG, IgA, IgM, IgD, and IgE. Each class acts slightly differently and responds to different threats.
Most antibodies in the blood and other bodily fluids belong to the IgG class — as do the self-reactive antibodies that contribute to developing myasthenia gravis (MG). In most MG patients, these antibodies target acetylcholine receptors (AChRs), proteins critical for nerve-muscle communication. Normally, a chemical messenger called acetylcholine binds to AChRs and signals muscles to contract. AChR-targeted antibodies in MG prevent acetylcholine from efficiently binding to its receptors and nerve cells cannot send a strong signal to the muscles, leading to symptoms of muscle weakness.
IgG antibodies circulating in the bloodstream are eventually broken down and recycled. A protein called neonatal Fc receptor (FcRn) helps to stabilize IgG antibodies and prevent their destruction.
Vyvgart works by blocking FcRn, thereby increasing the rate at which IgG antibodies, including those driving MG, are broken down. By lowering the levels of disease-driving antibodies, it’s expected to ease symptoms.
Vyvgart is not specific for MG-causing antibodies and will also act on other IgG antibodies produced by the immune system in response to infection.
Who can take Vyvgart?
Vyvgart was approved by the U.S. Food and Drug Administration (FDA) in December 2021 to treat adults with gMG who are positive for AChR antibodies. It was also approved for the same indication in Europe in August 2022.
The therapy is also approved in Japan to treat adults with gMG, regardless of antibody status, who failed to respond to other immunosuppressive therapies.
It’s currently under review in China and has been made available to some adults with gMG and AChR antibodies in the U.K. under an early access program.
Who should not take Vyvgart?
There are no known contraindications for Vyvgart’s use.
How is Vyvgart administered?
Vyvgart is administered via hour-long infusions into the bloodstream by a trained healthcare professional. Patients initially receive weekly infusions over four weeks, with additional treatment cycles administered based on their clinical response. The safety of initiating a new cycle sooner than 50 days from the start of the previous cycle has not been established.
The dose per infusion is 10 milligrams per kilogram of body weight (mg/kg), or 1,200 mg for patients who weight 120 kg (about 265 pounds) or more.
Vyvgart may decrease the effectiveness of vaccines. It’s recommended that patients receive all age-appropriate vaccinations before starting a new treatment cycle.
Other dosing schemes and a subcutaneous (under-the-skin) formulation of Vyvgart are currently being evaluated in clinical trials.
Vyvgart in clinical trials
ADAPT trial
Vyvgart’s approvals were largely supported by data from the Phase 3 ADAPT trial (NCT03669588). ADAPT evaluated the treatment’s safety and effectiveness in 167 adults with gMG, including 129 who were positive for anti-AChR antibodies.
Participants were randomized to receive a placebo or Vyvgart at the recommended into-the-vein dosing regimen, in addition to their current standard treatments, for 26 weeks, or about six months.
The trial’s main goal was to assess the percentage of patients who had clinically meaningful improvements in MG symptoms, as measured by a two-point or greater reduction in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score for at least four consecutive weeks compared with baseline measures.
Trial data showed that significantly more Vyvgart-treated patients with anti-AChR antibodies had meaningful improvements in MG-ADL scores during the first treatment cycle compared with those on a placebo (67.7% vs. 29.7%), meeting the trial’s main goal. A greater proportion of treated patients experienced a three or more point improvement in the Quantitative MG (QMG) questionnaire, another measure of MG symptom severity, compared with the placebo group (63.1% vs. 14.1%), meeting a secondary trial goal.
Vyvgart was also superior to a placebo in patients who did not have AChR antibodies, additional analyses showed. The treatment was generally safe and well tolerated.
ADAPT+ trial
After completing ADAPT, most participants (151 people) entered an open-label extension study called ADAPT+ (NCT03770403), wherein all were treated with Vyvgart for up to three years. Its main goals were to assess the treatment’s long-term safety and tolerability. An interim analysis from 106 patients with AChR antibodies and 33 without them showed that patients on Vyvgart demonstrated consistent improvements in MG-ADL and QMG scores for up to 10 treatment cycles.
ADAPT+ concluded in June 2022; final trial results have not yet been disclosed.
ADAPT-SC trial
The Phase 3 ADAPT-SC trial (NCT04735432) compared the effects of subcutaneous efgartigimod with the traditional into-the-vein Vyvgart formulation over 12 weeks. The trial enrolled 110 adults with gMG in North America, Europe, and Japan. Participants were randomly assigned to receive either four weekly subcutaneous doses of efgartigimod (1,000 mg) or Vyvgart at 10 mg/kg.
Results showed that subcutaneous efgartigimod was similar, or noninferior, to Vyvgart in its ability to lower IgG antibodies one week after the last dose, regardless of patients’ AChR antibody status. The safety profile of the two treatments was also similar, and the subcutaneous version led to improvements in MG-ADL and QMG scores consistent with those seen in the ADAPT trial of Vyvgart.
Ongoing trials
ADAPT NXT
The open-label Phase 3 ADAPT NXT trial (NCT04980495) is investigating the safety, tolerability, and effectiveness of a continuous regimen of Vyvgart compared with the approved four-week treatment cycles. The trial is recruiting up to 72 adults with gMG at sites worldwide. Participants will receive either a continuous or a cyclic treatment regimen of Vyvgart for 21 weeks, followed by an extension period of up to 105 weeks.
The study’s main goal is to assess the treatment’s effectiveness as measured by the change in MG-ADL scores at 21 weeks. Secondary goals include safety, tolerability, and other efficacy measures. The trial is expected to finish in 2025.
ADAPT-SC+
The ongoing Phase 3 ADAPT-Sc+ trial (NCT04818671) is investigating the long-term safety and tolerability of subcutaneous efgartigimod (1,000 mg) for up to two years in 183 adults with gMG who participated in ADAPT-SC or ADAPT+. Secondary trial goals include treatment efficacy, quality of life, treatment satisfaction, administration method preferences, and feasibility of self- or caregiver- administration.
That trial is expected to finish in April 2023.
Other trials
A Phase 2/3 trial (NCT04833894) is evaluating the safety and pharmacological properties of Vyvgart in children ages 2–18 with gMG. Up to 12 participants are being recruited at sites in Europe, all of whom will receive Vyvgart in the vein.
Primary trial goals include evaluating blood levels of Vyvgart and IgG levels after treatment. Secondary goals include safety, quality of life, and efficacy measures, as well as the response to vaccines after treatment. A long-term extension (NCT05374590) of that trial will evaluate the treatment’s safety for up to four years and is expected to finish in 2026.
Common side effects of Vyvgart
The most common side effects associated with Vyvgart’s use include:
- respiratory tract infections
- headache
- urinary tract infections
Infections
Patients using Vyvgart may be more susceptible to infections. The most commonly reported infections in clinical trials were those affecting the respiratory and urinary tract, with most infections reported being mild to moderate in severity.
Patients should be monitored for clinical signs of infection. It’s recommended that Vyvgart be withheld in patients experiencing a serious infection until it has resolved.
Allergic Reactions
Allergic reactions, including breathing difficulties, swelling and rash, have been reported in patients using Vyvgart. In clinical trials, these reactions were mild or moderate and occurred within one hour to three weeks of administration. They didn’t require treatment discontinuation, however.
Participants should be monitored during the administration of Vyvgart and for one hour after for signs of an allergic reaction. If an allergic reaction occurs, Vyvgart should be discontinued.
Pregnancy and Breastfeeding
There are no available data on using Vyvgart during pregnancy in humans or on the presence of Vyvgart in breast milk.
In preclinical studies, no evidence of abnormal fetal development was observed when mothers (rats or rabbits) were administered Vyvgart at doses up to 100 mg/kg per day. Administration of Vyvgart to rats during pregnancy and lactation resulted in no adverse developmental effects in utero or after birth.
Patients who are pregnant or wish to become pregnant or breastfeed while using Vyvgart should discuss this with their healthcare providers.
Since Vyvgart is anticipated to reduce maternal IgG levels, it’s expected that passive immune protection provided by the mother to the newborn will be reduced. Risk-to-benefit ratio should be considered by patients and their healthcare providers before administering vaccines to infants who were exposed to Vyvgart in utero.
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