Vyvgart (efgartigimod alfa-fcab) for myasthenia gravis

Last updated Oct. 28, 2024, by Joana Carvalho, PhD
Fact-checked by Inês Martins, PhD

What is Vyvgart for myasthenia gravis?

Vyvgart (efgartigimod alfa-fcab) is an approved infusion 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. It is administered intravenously, or via infusions directly into the bloodstream, to ease disease severity.

Vyvgart was developed by Argenx, which also markets another formulation of efgartigimod alfa that’s administered via subcutaneous, or under-the-skin, injections. That formulation, marketed under the brand name Vyvgart Hytrulo, is approved for the same indication.

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 MG 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 December 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 has 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?

Vyvgart is contraindicated, or not recommended, for patients with serious allergies to efgartigimod alfa or any other components of the therapy.

How is Vyvgart administered?

Vyvgart is given via hourlong 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.

During each infusion and for one hour thereafter, patients should be closely monitored for any signs of allergic reactions, and appropriate measures should be taken if such a reaction occurs.

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.

If a scheduled infusion is missed, the missing dose may be administered up to three days following the scheduled day. If more than three days have passed, the usual dosing schedule should be resumed until the treatment cycle is completed.

Because Vyvgart causes a temporary reduction in IgG levels, vaccination with live vaccines is not recommended during treatment. Before starting a new treatment cycle, the need to administer age-appropriate vaccines should be evaluated in all patients.

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 anti-AChR-positive patients who had clinically meaningful improvements in their MG symptoms. This was measured by a two point or greater reduction in the MG Activities of Daily Living (MG-ADL) score that was sustained for at least four consecutive weeks.

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 that Vyvgart 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, 151 participants 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 involved 111 patients with anti-AChR antibodies and 34 without them who received at least one dose of Vyvgart. The results showed that Vyvgart led to consistent improvements in MG-ADL and QMG scores across multiple treatment cycles, regardless of antibody status.

Clinically meaningful improvements in both measures of MG severity were seen as early as one week following the first infusion across multiple cycles in both patient populations. Maximum clinical improvements seen during each treatment cycle were associated with greater reductions in IgG and anti-AChR antibody levels.

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 duration, treatment history, or anti-AChR antibody status.

Ongoing trials

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 69 adults with gMG received either a continuous or a cyclic treatment regimen of Vyvgart for 21 weeks, or about five months, 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.

Study data announced thus far showed that both dosing regimens led to clinically meaningful reductions in MG-ADL scores, which dropped by approximately five points after 21 weeks. Vyvgart was also found to be well tolerated in both treatment regimens.

A Phase 2/3 trial called ADAPT JR (NCT04833894) is also evaluating the safety and pharmacological properties of Vyvgart in children and adolescents ages 2-17 with gMG. An estimated 12 participants will be enrolled at sites in Canada, Europe, and the U.S. and 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 of that trial called ADAPT JR+ (NCT05374590) will then evaluate the treatment’s safety for up to four years. This extension, which will also include participants given subcutaneous Vyvgart Hytrulo in a similar pediatric trial, is expected to finish in 2028.

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. In postmarketing studies, a severe and potentially life-threatening allergic reaction called anaphylaxis and low blood pressure resulting in fainting have occurred during or within one hour of administration. In some cases, these reactions led to permanent treatment discontinuation.

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

Infusion-related reactions

Infusion-related reactions have been reported in patients treated with Vyvgart in postmarketing studies. The most common symptoms of such reactions included high blood pressure, chills, shivering, and pain in the chest, abdomen, and back. These reactions occurred during or within one hour after administration and led to infusion discontinuation.

Vyvgart administration should be stopped and appropriate treatment given if a severe infusion-related reaction occurs. The benefits and risks of readministering Vyvgart should be considered in patients who have experienced a severe infusion-related reaction. In those having a mild to moderate reaction, patients may restart the therapy with close clinical observation, slower infusion rates, and premedications.

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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