Vyvgart (efgartigimod) for myasthenia gravis

Last updated July 7, 2023, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD

What is Vyvgart for myasthenia gravis?

Vyvgart (efgartigimod alfa-fcab) is an approved injection therapy for adults with generalized myasthenia gravis (gMG) who are positive for antibodies targeting the acetylcholine receptor (AChR) — the most common type of MG-causing antibody.

Formerly known as ARGX-113, the drug was developed by Argenx.

Therapy snapshot

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 driving the neuromuscular condition myasthenia gravis (MG).

In most MG patients, these antibodies target AChR, a protein 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. Thus, 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, the therapy is expected to ease disease symptoms.

Vyvgart is not specific for MG-causing antibodies and also will 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 in 2021 to treat adults with gMG who are positive for anti-AChR antibodies. This marked the first approval of an FcRn blocker in the U.S. and also made the treatment the first approved therapy designed to reduce disease-causing IgGs.

The medication also been approved as an add-on to standard therapy for adults with gMG who are positive for anti-AChR antibodies in the European Union and the U.K. In Japan, Vyvgart is approved to treat adults with gMG, regardless of antibody status, who failed to respond to other immunosuppressive therapies.

Who should not take Vyvgart?

There are no known contraindications for Vyvgart’s use.

However, the administration of Vyvgart should be delayed in patients with an active infection until the infection is resolved.

Vyvgart also has been associated with hypersensitivity reactions, including rash, swelling of the deeper layers of the skin, and shortness of breath; treatment might need to be discontinued in patients who have such reactions.

How is Vyvgart administered?

Vyvgart is given via hour-long infusions into the bloodstream by a trained healthcare professional.

Patients initially receive a treatment cycle of once weekly infusions over four weeks. Additional treatment cycles of four once-weekly injections each are then 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 recommended dose per infusion is 10 milligrams per kilogram of body weight (mg/kg) for patients weighing less than 120 kg (about 265 pounds). Those who weigh 120 kg or more should instead receive a 1,200 mg dose in each infusion.

Vyvgart may decrease the effectiveness of vaccines. It’s recommended patients receive all age-appropriate vaccinations before starting a new treatment cycle. Vaccination with live-attenuated or live vaccines is not recommended during treatment.

Vyvgart in clinical trials

Vyvgart’s approvals were largely supported by data from the Phase 3 ADAPT trial (NCT03669588), completed in 2020.

ADAPT trial

ADAPT evaluated Vyvgart’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 their myasthenia gravis symptoms. This was measured by a two point or greater reduction, for at least four consecutive weeks, in the MG Activities of Daily Living (MG-ADL) score, as compared with baseline measures.

Trial data showed 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 also 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%). That finding meant Vyvgart met a secondary trial goal.

Vyvgart also was superior to a placebo in both measures when given in a second treatment cycle. Also, about one-third of patients who had not experienced meaningful improvements in MG-ADL scores in the first cycle did so in the second.

Additional exploratory analyses also showed it was more effective than a placebo at improving QMG scores in patients who did not have anti-AChR antibodies, but no differences were observed in MG-ADL scores. The treatment was generally safe and well tolerated.

ADAPT+ trial

After completing ADAPT, most participants (151 individuals) 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 anti-AChR antibodies and 33 without them showed patients on Vyvgart demonstrated consistent improvements in MG-ADL and QMG scores for up to 10 treatment cycles. A more recent analysis involving a total of 145 patients and a mean follow-up of nearly two years showed Vyvgart led to consistent and repeatable improvements in measures of disease severity.

Additional analyses from ADAPT and ADAPT+ also demonstrated Vyvgart was effective at easing MG symptoms, regardless of disease length, treatment history, or anti-AChR antibody status.

Ongoing trials

ADAPT NXT

The open-label Phase 3b ADAPT NXT trial (NCT04980495) is investigating the safety, tolerability, and effectiveness of a continuous regimen of Vyvgart compared with the approved four-week cyclic treatment. A total of 72 adults with gMG will receive either a continuous or a cyclic treatment regimen of Vyvgart for 21 weeks, or about five months. This will be followed by an extension period of up to 105 weeks, or about two years.

The study’s main goal is to assess the treatment’s effectiveness, as measured by changes in MG-ADL scores at 21 weeks. Secondary goals include safety, tolerability, and other efficacy measures. The trial is expected to finish in 2025.

Other trials

A Phase 2/3 trial (NCT04833894) is evaluating the safety and pharmacological properties of Vyvgart in children ages 2-18 with gMG. An estimated 12 participants are being recruited at sites in the U.S. and Europe. All will receive Vyvgart in the recommended schedule.

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 vaccine response 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 of Vyvgart reported in clinical trials of gMG patients were:

• respiratory tract infections
• headache
• urinary tract infections.

Infections

Individuals using Vyvgart may be more susceptible to infections. The most commonly reported infections in clinical trials were those affecting the respiratory and urinary tracts, with most of those reported being mild to moderate in severity.

Patients should be monitored for clinical signs of infection. It’s recommended 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 after administration. They did not lead to treatment discontinuation, however.

Patients should be monitored during Vyvgart’s administration and for one hour afterward for signs of an allergic reaction. If an allergic reaction occurs, Vyvgart should be discontinued.

Use in pregnancy and breastfeeding

There are no available data regarding the use of Vyvgart during pregnancy or the presence of the medication in breast milk. In preclinical studies with rats and rabbits, no evidence of abnormal fetal development was observed when pregnant animals were given Vyvgart at doses up to 100 mg/kg per day.

Patients who are pregnant or wish to become pregnant or breastfeed while using Vyvgart should discuss this with their healthcare providers.

Because Vyvgart is anticipated to reduce maternal IgG levels, it’s expected that passive immune protection typically 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 the womb.

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