Description
Efgartigmod alfa-fcab (Vygart™) is an antibody fragment that binds to the neonatal Fc receptor (FcRn). The blockade of FcRn reduces IgG antibody levels, including the abnormal antiacetylcholine receptor (AChR) antibodies that are present in patients with generalized myasthenia gravis (gMG). In patients with myasthenia gravis who test positive for the antiacetylcholine receptor (AChR) antibody, the AChR antibodies interfere with communication between nerves and muscles, resulting in weakness.

Background
Vyvgart is a first-in-class human immunoglobulin G1 (IgG1) antibody fragment indicated for the treatment of generalized myasthenia gravis in adults with anti-acetylcholine receptor antibodies. It binds to the neonatal Fc receptor (FcRn) causing the antibodies to stay in circulation and preventing FcRn from recycling IgG back into the blood. This leads to a reduction in the overall levels of IgG, including the abnormal AChR antibodies that are present in most patients with generalized myasthenia gravis. Vyvgart is administered as a 10 mg/kg intravenous infusion over 1 hour once weekly for 4 weeks. In patients weighing 120 kg or more, the recommended dose is 1200 mg per infusion. If subsequent treatment cycles are needed (determined based on clinical evaluatio n), they should be initiated no sooner than 50 days from the start of the previous treatment cycle. It should be noted that this drug causes a reduction in IgG levels, so immunization with live-attenuated or live vaccines is not recommended during treatment. If indicated, these vaccines should be administered prior to initiation of a Vyvgart treatment cycle.

Myasthenia gravis is a chronic autoimmune neuromuscular disease that causes weakness in the skeletal muscles. The hallmark of the condition is muscle weakness that worsens after periods of activity and improves after periods of rest. Certain muscles such as those that control eye and eyelid movement, facial expression, chewing, talking, and swallowing are often involved in the disorder; however, the muscles that control breathing and neck and limb movements may also be affected. Acquired myasthenia gravis results from the binding of autoantibodies to components of the neuromuscular junction, most commonly the acetylcholine receptor (AChR). However, antibodies to other proteins, such as the muscle-specific kinase (MuSK) protein, can also lead to impaired transmission at the neuromuscular junction. Myasthenia gravis most commonly occurs in young adult women (60 years of age), but it can occur at any age, including childhood. The incidence ranges from 0.3 to 2.8 per 100,000, and it is estimated to affect more than 700,000 people worldwide. Various clinical scoring systems are available to assess the severity of disease and include the Myasthenia Gravis Foundation of America (MGFA) clinical classification system, Myasthenia Gravis Activities of Daily Living (MG-ADL), and Quantitative Myasthenia Gravis (QMG) test.

Medications to treat myasthenia gravis include anticholinesterase agents (e.g., pyridostigmine), which slow the breakdown of acetylcholine at the neuromuscular junction and thereby improve neuromuscular transmission and increase muscle strength. Immunosuppressive drugs improve muscle strength by suppressing the production of abnormal antibodies and may include prednisone, azathioprine, mycophenolate mofetil, tacrolimus, and rituximab. Plasmapheresis and intravenous immunoglobulin (IVIG) may be options in severe cases to remove the destructive antibodies; however, their effectiveness frequently lasts only a few weeks to months. Additionally, the Food and Drug Administration (FDA) recently approved eculizumab (Soliris®) ‡ and ravulizumab (Ultomiris™) ‡ , both complement inhibitors, for the treatment of generalized myasthenia gravis. Although Soliris, Ultomiris, and Vyvgart are the only agents with FDA approval for the condition, the other agents have been used off-label and are still recommended as first-line therapy in clinical practice guidelines. Available guidelines have not been updated to address Vyvgart.

Regulatory Status
Vyvgart was approved in December 2021 for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Policy
Initial criteria

1. Used for the treatment of generalized myasthenia gravis (gMG) in adults, AND
2. Member has positive serologic test for anti-AChR antibodies, AND
3. Medication is prescribed by, or in consultation with, a neurologist, AND
4. Member meets one of the following:
   1. Prescribed medication will be administered at 10mg/kg as an intravenous infusion once weekly for 4 weeks, or
   2. For members weighing 120 kg or more, prescribed medication will be administered at 1200mg per infusion over one hour once weekly for 4 weeks, AND
5. Member has a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score ≥ 5 at baseline, AND
6. Member has a Myasthenia Gravis Foundation of America (MGFA) clinical classification of Class II to IV at baseline, AND
7. Prior to treatment, member must be on a stable dose of at least one of the following therapies for the treatment of gMG:
   1. Acetylcholinesterase (AChE) inhibitors (e.g., pyridostigmine)
   2. Steroids (e.g., prednisone)
   3. Non-steroidal immunosuppressive therapies (NSISTs) [e.g., azathioprine, cyclosporine, cyclophosphamide), AND
8. Medication will not be used in combination with Soliris^®

Auth duration: 6 months

Reauthorization criteria

1. Documentation that member is responsive to therapy as demonstrated by a 2-point reduction in MG-ADL score from baseline while on therapy, AND
2. Maintenance, reduction, or discontinuation of dose(s) of baseline immunosuppressive therapy (IST) prior to starting Vyvgart.  Note: Add on, dose escalation of IST, or additional rescue therapy from baseline to treat myasthenia gravis or exacerbation of symptoms while on Vyvgart therapy will be considered as treatment failure.
3. Medication is prescribed by, or in consultation with, a neurologist, AND
4. Member meets one of the following:
   1. Prescribed medication will be administered at 10mg/kg as an intravenous infusion once weekly for 4 weeks, or
   2. For members weighing 120 kg or more, prescribed medication will be administered at 1200mg per infusion over one hour once weekly for 4 weeks, AND
5. Myasthenia Gravis Foundation of America (MGFA) clinical classification of Class II to IV

Auth duration: 12 months

Rationale
This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. Food and Drug Administration approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

The efficacy of Vyvgart for the treatment of generalized myasthenia gravis in adults who are AChR antibody positive was established in a 26-week, multicenter, randomized, double-blind, placebo-controlled trial. Included patients had a Myasthenia Gravis Foundation of America (MGFA) clinical classification class II to IV, MG-ADL total score of > 5, and were on a stable dose of myasthenia gravis therapy prior to screening that included acetylcholinesterase (AChE) inhibitors, steroids, or NSISTs, either in combination or alone. Additionally, patients had IgG levels of at least 6 g/L. A total of 167 patients were enrolled and were randomized to receive either Vyvgart 10 mg/kg (1200 mg for those weighing 120 kg or more) (n = 84) or placebo (n = 83). At baseline, over 80% of patients in each group received AChE inhibitors, over 70% in each group received steroids, and approximately 60% in each treatment group received NSISTs, at stable doses.

The efficacy of Vyvgart was measured using the Myasthenia Gravis-Specific Activities of Daily Living (MG-ADL) scale, which assesses the impact of generalized myasthenia gravis on daily functions of 8 signs or symptoms that are typically affected in the condition. Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. A total score ranges from 0 to 24, with the higher scores indicating more impairment. In this study, an MG-ADL responder was defined as patient with a 2-point or greater reduction in the total MG-ADL score compared to the treatment cycle baseline for at least 4 consecutive weeks, with the first reduction occurring no later than 1 week after the last infusion of the cycle. The primary efficacy endpoint was the comparison of the percentage of MG-ADL responders during the first treatment cycle between treatment groups in the AChR-Ab positive population. A statistically significant difference favoring Vyvgart was observed in the MG-ADL responder rate during the first treatment cycle [67.7% in the Vyvgart-treated group vs 29.7% in the placebo-treated group (p < 0.0001)].

References

1. Vyvgart [package insert]. Argenx US. Boston, MA. Updated February 2022.
2. Muppidi S, Wolfe GI, Conaway M, Burns TM. MG composite and MG-QOL 15 study group. MG AD: still a relevant outcome measure. Muscle Nerve, 2011;44(5):727-731.
3. Jaretzki A 3rd, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, Sanders DB. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology. 2000;55(1):16-23.
4. Barohn RJ, McIntire D, Herbelin L, Wolfe GI, Nations S, Bryan WW. Reliability testing of the quantitative myasthenia gravis score. Ann NY Acad Sci. 1998;841:769-772.
5. Vyvgart Drug Evaluation. Express Scripts. Updated January 2022.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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