Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.
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Vyvgart
Vyvgart™ (efgartigimod alfa-fcab) is a medication indicated for treating generalized myasthenia gravis (gMG) in adults. Patients must be anti-acetylcholine receptor (AChR) antibody-positive to receive this therapy.1
Generalized MG is a rare autoimmune disease characterized by debilitating muscle weakness that affects the muscles of the eyes, limbs, throat, face, and jaw. The disease can also compromise respiratory muscles, leading to myasthenic crisis, which is a life-threatening condition.2
In nearly 90% of patients, the development of gMG is driven by the formation of immunoglobulin G (IgG) autoantibodies against different components of the neuromuscular junction, including the nicotinic AChR.3 These autoantibodies are able to compromise synaptic transmission and muscle contraction.2,4
Read more about prescribing information for Vyvgart (Efgartigimod Alfa-fcab) at MPR.com
Mechanism of Action and Use of Vyvgart
The active ingredient of Vyvgart is efgartigimod alfa-fcab, a human IgG1-derived Fc fragment that is mutated in 5 residues and capable of binding to the neonatal Fc receptor (FcRn).1,4 This receptor is a key player in IgG homeostasis, promoting IgG recycling and avoiding IgG lysosomal degradation.3,4 The mutations carried by efgartigimod alfa-facb confer to this molecule a higher binding affinity to the FcRn at physiologic pH. Binding to the FcRn results in the promotion of IgG removal and a consequent reduction in circulating IgG.1,3
Vyvgart, by Argenx, is the first FcRn blocker that has been approved by the US Food and Drug Administration (FDA). It was approved in December 2021, and it can be prescribed to anti-AChR antibody-positive patients, which represent about 85% of the gMG population.5,6
The administration of Vyvgart is performed intravenously with a recommended dose of 10 mg/kg, or 1200 mg if the patient weighs at least 120 kg. Patients should receive an infusion over 1 hour once a week for 4 weeks. Further administrations require a clinical evaluation.1
As Vyvgart decreases IgG levels, it may consequently increase the risk of infection. Patients with active infections should therefore delay the infusions. Vaccination with live-attenuated or live vaccines is not recommended during treatment.1
The most common adverse reactions associated with Vyvgart administration include respiratory tract infection, urinary tract infection, and headache.1
Vyvgart in Clinical Trials
In a phase 1 randomized, placebo-controlled study (NCT03457649), efgartigimod alfa-fcab (ARGX-113) was evaluated to determine its safety, tolerability, pharmacokinetic properties, and immunogenicity. Different doses and dose regimens were assessed. The results of this trial showed that a single administration of efgartigimod alfa-fcab reduced IgG levels up to 50% and that multiple doses promoted a 75% decrease in IgG levels from baseline on average. No serious adverse events were reported after the administration of the drug.7
Results from the phase 1 clinical trial supported a following phase 2 trial that evaluated the safety, efficacy, and pharmacokinetics of efgartigimod alfa-fcab in patients with gMG (NCT02965573). This was a randomized, double-blind, placebo-controlled, multicenter trial that enrolled patients already receiving a stable standard-of-care treatment for MG.4 Twenty-four patients were randomized to receive either efgartigimod or a placebo. No severe adverse events were reported, and the drug was shown to induce a decrease in anti-AChR antibodies and total IgG levels, with 75% of patients experiencing long-lasting disease improvement.4
The safety and efficacy of efgartigimod was studied in 167 participants, including 129 with anti-AChR antibodies, in a phase 3 clinical trial, ADAPT (NCT03669588). This randomized, double-blind, placebo-controlled trial was performed in 15 countries. Participants were randomized to receive efgartigimod or placebo in addition to their current treatment. Patients in the efgartigimod group received weekly infusions of 10 mg/kg over 4 weeks, which could be repeated as needed according to clinical response no sooner than 8 weeks after the start of the last cycle. The duration of the trial was 26 weeks. The main outcome of the study was to ascertain the percentage of anti-AChR antibody-positive patients who responded to the treatment. Participants in the efgartigimod group showed significant clinical improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score compared to the placebo group. The observed response to treatment lasted for at least 6 to 12 weeks. Overall, efgartigimod alfa-fcab was well tolerated, and the most common adverse events reported were headache and nasopharyngitis.8
Following the ADAPT trial, 151 of its participants were enrolled in an open-label extension study, ADAPT+ (NCT03770403). This trial focuses on evaluating the long-term safety and efficacy of efgartigimod alfa-fcab in patients that have completed at least 1 cycle of treatment and at least 1 year in the ADAPT trial. ADAPT+ is currently active and not recruiting.9
References
1.Vyvgart. Prescribing information. Argenx; 2021. Accessed February 17, 2022.
2. Myasthenia gravis. National Organization for Rare Disorders (NORD). Accessed February 17, 2022.
3. Guidon AC, Juel VC. Efgartigimod: a novel antibody depletion therapy in myasthenia gravis. Neurology. 2019;92(23):1079-1080. doi:10.1212/WNL.0000000000007605
4. Howard JF Jr, Bril V, Burns TM, et al; Efgartigimod MG Study Group. Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Neurology. 2019;92(23):e2661-e2673. doi:10.1212/WNL.0000000000007600
5. Argenx announces U.S. Food and Drug Administration (FDA) approval of Vyvgart™ (efgartigimod alfa-fcab) in generalized myasthenia gravis. News release. Argenx; December 17, 2021.
6. Behin A, Le Panse R. New pathways and therapeutic targets in autoimmune myasthenia gravis. J Neuromuscul Dis. 2018;5(3):265-277. doi:10.3233/JND-170294
7. Ulrichts P, Guglietta A, Dreier T, et al. Neonatal Fc receptor antagonist efgartigimod safely and sustainably reduces IgGs in humans. J Clin Invest. 2018;128(10):4372-4386. doi:10.1172/JCI97911
8. Howard JF Jr, Bril V, Vu T, et al; ADAPT Investigator Study Group. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2021;20(7):526-536. doi:10.1016/S1474-4422(21)00159-9
9. A safety and tolerability study of ARGX-113 in patients with myasthenia gravis who have generalized muscle weakness. (ADAPT+). ClinicalTrials.gov. December 10, 2018. Updated May 24, 2021. Accessed February 17, 2022.
Reviewed by Kyle Habet, MD, on 2/22/2022.
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