In December 2021, Vyvgart was approved by the U.S. Food and Drug Administration to treat adults with gMG who are positive for anti-acetylcholine receptor (AChR) antibodies — the most common type of MG-causing antibody. The therapy also has been approved in Japan to treat adults with gMG, regardless of antibody status, who failed to respond to steroids or nonsteroidal immunosuppressive therapies.
Vyvgard had been awarded orphan drug status in both the U.S. and Europe. That designation is given to therapies for rare diseases, which is classified in the U.S. as a disorder affecting fewer than 200,000 people, and in the EU as diagnosed in not more than five in 10,000 people.
How does Vyvgart work?
Antibodies are proteins that the immune system produces in response to foreign molecules invading the body. Also known as immunoglobulins, 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 fluid that surround tissues and cells belong to the IgG class.
The self-reactive antibodies that contribute to MG development and progression also belong to the IgG class. In most patients, these autoantibodies target the acetylcholine receptor — a protein that binds to the neurotransmitter acetylcholine and plays a key role in nerve-muscle communication.
Normally, the binding of acetylcholine to its receptor signals muscles to contract. However, because the immune system attacks acetylcholine receptors in MG, acetylcholine cannot bind to them efficiently and nerve cells cannot send a strong signal to muscles, resulting in muscle weakness.
Normally, 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 this process. 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 antibodies that cause MG, however. The medication will also act on antibodies produced by the immune system in response to infections.
Vyvgart in clinical trials
In Phase 1 studies, researchers demonstrated that Vyvgart (formerly known as ARGX-113) had favorable safety and tolerability with different doses and dosing regimens. They also showed treatment led to promising reductions in the levels of disease-causing IgGs.
A Phase 2 study (NCT02965573) to assess the safety, efficacy, and pharmacological properties of Vyvgart in MG patients with generalized muscle weakness has been completed. Researchers administered Vyvgart in addition to patients’ current treatment, which included cholinesterase inhibitors, corticosteroids, or immunosuppressants.
Results showed that 75% of patients treated with Vyvgart had clinically and statistically significant improvements through at least six weeks, compared with 25% of those on placebo. Researchers reported no severe side effects.
A Phase 3 clinical called ADAPT (NCT03669588) evaluated Vyvgart’s safety and effectiveness in 167 adults with MG, including 129 who were positive for anti-AChR antibodies. Participants were randomized to either Vyvgart at 10 milligrams/kilogram (mg/kg) — administered in single weekly infusion cycles over four weeks, with a maximum of three rounds of treatment — or to a placebo, in addition to their current standard treatments, for 26 weeks (about six months).
Trial results showed that significantly more AChR-positive patients treated with Vyvgart showed clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living score, a measure of MG symptom severity, than those on a placebo (67.7% vs. 29.7%), meeting the trial’s main goal. The therapy was also associated with fast, deep, and durable responses among treated patients. Further analyses also showed that Vyvgart was superior to a placebo among AChR-negative patients.
Treatment was generally well tolerated, with a safety profile comparable with that of placebo.
After completing ADAPT, most participants (about 91%) entered an open-label extension study called ADAPT+ (NCT03770403), in which all enrolled will be treated with Vyvgart for up to three years. Its main goals are to assess the treatment’s safety and tolerability for long-term use, and researchers expect to complete ADAPT+ in mid-2023.
Vyvgart is administered via hour-long infusions into the bloodstream. Patients initially receive four weekly infusions over the course of four weeks, with additional treatment cycles administered based on clinical response. The dosage per infusion is 10 mg/kg, or 1200 mg for patients who weight 120 kg (about 265 pounds) or more.
Its most common side effects (affecting 10% or more of patients) include respiratory tract infections, headache, and urinary tract infection. Allergic reactions to Vyvgart can occur, in which case treatment should be stopped and appropriate therapies given.
Because Vyvgart interacts with the immune system, it may make patients more susceptible to infections. It is recommended that treatment with Vyvgart be withheld if a patient is currently experiencing a serious infection. Vyvgart also may decrease the effectiveness of vaccines; as such, it is recommended that patients receive all age-appropriate vaccinations before initiating a new treatment cycle.
Argenx opened “My Vyvgart Path,” a program offering patients and clinicians in the U.S. support, product education, and financial assistance information, among other resources.
Last updated: Jan. 13, 2022, by Marisa Wexler MS
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