Nipocalimab-aahu (Imaavy)

Number: 1083

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Brand Selection for Medically Necessary Indications for Commercial Medical Plans

According to Aetna commercial benefit plans, health care services are considered not medically necessary if they are more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that member’s illness, injury or disease. Aetna commercial plans may require a trial of a lower-cost drug (preferred medication) that is at least as likely to produce equivalent therapeutic results before approving coverage for a higher-cost drug within the same therapeutic class. For a list of preferred drugs, refer to the Aetna Commercial Clinical Program Summary.

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses nipocalimab-aahu (Imaavy) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of nipocalimab-aahu (Imaavy) is required of all Aetna participating providers and members in applicable plan designs. For precertification of nipocalimab-aahu (Imaavy), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

Note: Site of Care Utilization Management Policy applies. For information on site of service for nipocalimab-aahu (Imaavy), see Utilization Management Policy on Site of Care for Specialty Drug Infusions.

1. Prescribing Specialties

   This medication must be prescribed by or in consultation with a neurologist.

2. Exclusions 

   The requested medication will not be used in combination with another neonatal Fc receptor blocker (e.g., Rystiggo, Vyvgart, Vyvgart Hytrulo), or complement inhibitor (e.g., Soliris, Ultomiris, Zilbrysq), or Uplizna.

3. Criteria for Initial Approval

   Aetna considers nipocalimab-aahu (Imaavy) medically necessary for the treatment of generalized myasthenia gravis (gMG) when all of the following criteria are met:

   1. Anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive; and
   2. Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV; and
   3. MG activities of daily living (MG-ADL) total score of greater than or equal to 5; and
   4. Meets one of the following:
      
      
      1. Member has had an inadequate response or intolerable adverse event to at least two immunosuppressive therapies over the course of at least 12 months (e.g., azathioprine, corticosteroids, cyclosporine, methotrexate, mycophenolate, tacrolimus); or
      2. Member has had an inadequate response or intolerable adverse event to at least one immunosuppressive therapy and intravenous immunoglobulin (IVIG) over the course of at least 12 months; or
      3. Member has a documented clinical reason to avoid therapy with immunosuppressive agents and IVIG.

   Aetna considers all other indications as experimental, investigational, or unproven.

4. Continuation of Therapy

   Aetna considers continuation of nipocalimab-aahu (Imaavy) therapy medically necessary for members requesting reauthorization when there is no evidence of unacceptable toxicity or disease progression while on the current regimen and member demonstrates a positive response to therapy (e.g., improvement in MG-ADL score, MG Manual Muscle Test (MMT), MG Composite).

5. Related Policies 

   1. CPB 0206 - Parenteral Immunoglobulins
   2. CPB 0285 - Plasmapheresis/Plasma Exchange/Therapeutic Apheresis
   3. CPB 0314 - Rituximab
   4. CPB 0807 - Eculizumab
   5. CPB 0946 - Ravulizumab-cwvz (Ultomiris)
   6. CPB 0975 - Inebilizumab-cdon (Uplizna)
   7. CPB 1002 - Efgartigimod Alfa-fcab (Vyvgart) and Efgartigimod Alfa and Hyaluronidase-qvfc (Vyvgart Hytrulo)
   8. CPB 1035 - Rozanolixizumab-noli (Rystiggo)

Dosage and Administration

Note: Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines. See Medical Specialty Medication Quantity Limits for more information. Below includes dosing recommendations as per the FDA-approved prescribing information.

Nipocalimab-aahu is available as Imaavy and is supplied in the following dosage forms and strengths for intravenous use:

• 300 mg/1.62 mL (185 mg/mL) in a single-dose vial
• 1,200 mg/6.5 mL (185 mg/mL) in a single-dose vial.

The recommended initial dosage is 30 mg/kg once via intravenous infusion over at least 30 minutes. Two weeks after the initial dosage, Imaavy is administered as a maintenance dosage of 15 mg/kg via intravenous infusion over at least 15 minutes, and continued every two weeks thereafter.  The single-dose vials must be diluted with 0.9% sodium chloride injection prior to administration. Moreover, the need to administer age-appropriate vaccines should be evaluated according to immunization guidelines before initiation of Imaavy. 

Source: Janssen Biotech, 2025

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
0545U	Acetylcholine receptor (AChR), antibody identification by immunofluorescence, using live cells, reported as positive or negative
86041	binding antibody
86042	blocking antibody
86043	modulating antibody
86366	Muscle-specific kinase (MuSK) antibody
90283	Immune globulin (IgIV), human, for intravenous use
90284	Immune globulin (SCIg), human, for use in subcutaneous infusions, 100 mg, each
96413 - 96417	Chemotherapy administration
HCPCS codes covered if selection criteria are met:
J9256	Injection, nipocalimab-aahu, 3 mg
Other HCPCS codes related to the CPB:
Zilbrysq – no specific code
J0702	Injection, betamethasone acetate and betamethasone sodium phosphate, per 3 mg
J1100	Injection, dexamethasone sodium phosphate, 1 mg
J1299	Injection, eculizumab, 2 mg
J1303	Injection, ravulizumab-cwvz, 10 mg
J1459	Injection, immune globulin (Privigen), intravenous, nonlyophilized (e.g., liquid), 500 mg
J1551	Injection, immune globulin (cutaquig), 100 mg
J1552	Injection, immune globulin (alyglo), 500 mg
J1554	Injection, immune globulin (asceniv), 500 mg
J1555	Injection, immune globulin (Cuvitru), 100 mg
J1556	Injection, immune globulin (bivigam), 500 mg
J1557	Injection, immune globulin, (gammaplex), intravenous, non-lyophilized (e.g., liquid), 500 mg
J1558	Injection, immune globulin (xembify), 100 mg
J1559	Injection, immune globulin (hizentra), 100 mg
J1561	Injection, immune globulin, (Gamunex-c/Gammaked), nonlyophilized (e.g. liquid), 500 mg
J1566	Injection, immune globulin, intravenous, lyophilized (e.g., powder), not otherwise specified, 500 mg
J1568	Injection, immune globulin, (Octagam), intravenous, nonlyophilized (e.g., liquid), 500 mg
J1569	Injection, immune globulin, (Gammagard liquid), nonlyophilized, (e.g. liquid), 500 mg
J1572	Injection, immune globulin, (Flebogamma / Flebogamma Dif), intravenous, nonlyophilized (e.g., liquid), 500 mg
J1575	Injection, immune globulin/hyaluronidase, (hyqvia), 100 mg immuneglobulin
J1576	Injection, immune globulin (panzyga), intravenous, non-lyophilized (e.g., liquid), 500 mg
J1599	Injection, immune globulin, intravenous, non-lyophilized (eg, liquid), not otherwise specified, 500 mg
J1700	Injection, hydrocortisone acetate, up to 25 mg (Hydrocortone acetate)
J1823	Injection, inebilizumab-cdon, 1 mg
J2650	Injection, prednisolone acetate, up to 1 ml
J3300	Injection, triamcinolone acetonide, preservative free, 1 mg
J3301	Injection, triamcinolone acetonide, per 10 mg
J3302	Injection, triamcinolone diacetate, per 5 mg
J3303	Injection, triamcinolone hexacetonide, per 5 mg
J7500	Azathioprine, oral, 50 mg
J7501	Azathioprine, parenteral, 100 mg
J7502	Cyclosporine, oral, 100 mg
J7503	Tacrolimus, extended release, (envarsus xr), oral, 0.25 mg
J7507	Tacrolimus, immediate release, oral, 1 mg
J7508	Tacrolimus, extended release, (astagraf xl), oral, 0.1 mg
J7509	Methylprednisolone, oral, per 4 mg
J7510	Prednisolone, oral, per 5 mg
J7512	Prednisone, immediate release or delayed release, oral, 1 mg
J7514	Mycophenolate mofetil (myhibbin), oral suspension, 100 m
J7515	Cyclosporine, oral, 25 mg
J7516	Injection, cyclosporine, 250 mg
J7517	Mycophenolate mofetil, oral, 250 mg
J7519	Injection, mycophenolate mofetil, 10 mg
J7521	Tacrolimus, granules, oral suspension, 0.1 mg
J7525	Tacrolimus, parenteral, 5 mg
J7528	Mycophenolate mofetil, for suspension, oral, 100 mg
J8540	Dexamethasone, oral, 0.25 mg
J8610	Methotrexate; oral, 2.5 mg
J8611	Methotrexate (jylamvo), oral, 2.5 mg
J8612	Methotrexate (xatmep), oral, 2.5 mg
J9255	Injection, methotrexate (accord) not therapeutically equivalent to j9250 and j9260, 50 mg
J9260	Injection, methotrexate sodium, 50 mg
J9332	Injection, efgartigimod alfa-fcab, 2mg
J9333	Injection, rozanolixizumab-noli, 1 mg
J9334	Injection, efgartigimod alfa, 2 mg and hyaluronidase-qvfc
Q5151	Injection, eculizumab-aagh (epysqli), biosimilar, 2 mg
Q5152	Injection, eculizumab-aeeb (bkemv), biosimilar, 2 mg
ICD-10 codes covered if selection criteria are met:
G70.00 - G70.01	Myasthenia gravis [Generalized]

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Imaavy is indicated for the treatment of generalized myasthenia gravis (gMG) in adult and pediatric patients 12 years of age and older who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.

Nipocalimab-aahu, branded as Imaavy (Janssen Biotech, Inc.), is a human IgG1 monoclonal antibody that acts as a neonatal Fc receptor (FcRn) blocker, resulting in reduced circulating IgG levels. Nipocalimab-aahu works in the treatment of generalized myasthenia gravis (gMG) in anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive patients by binding to the neonatal Fc receptor (FcRn), thereby reducing circulating IgG levels, including pathogenic autoantibodies. This reduction in IgG leads to decreased levels of AChR and MuSK autoantibodies, which are implicated in the pathogenesis of gMG.

Labeled warnings and precautions for Imaavy include risk of infections, hypersensitivity reactions, and infusion-related reactions.

• Infection risk: in a clinical study, 42 (43%) out of 98 patients treated with nipocalimab-aahu reported 71 events of infection. In the double blind period and open label-period of the extension study, out of 186 patients treated with nipocalimab-aahu, 132 (71%) patients reported 360 events of infection. Serious infections were reported in 7% of patients treated with nipocalimab-aahu. Patients treated may be at an increased risk of activation of latent viral infections, such as herpes zoster. In the extension period of the clinical study, there were 2 patients with serious adverse reactions related to Epstein-Barr virus (EBV) infection, with 1 who had fatal complications. Patients who screened positive for hepatitis were excluded from the study. The safety of immunization with live vaccines and the immune response to vaccination during treatment with nipocalimab-aahu are unknown.
• Hypersensitivity reactions: in clinical trials, hypersensitivity reactions, including angioedema, anaphylaxis, rash, urticaria, and eczema were observed in patients treated with nipocalimab-aahu. In a clinical study, hypersensitivity reactions were mild or moderate, occurred within one hour to 2 weeks of administration. One patient experienced a urticaria that led to treatment discontinuation.
• Infusion-related reactions: in clinical trials, infusion-related reactions, including headache, influenza-like illness, rash, nausea, fatigue, dizziness, chills, and erythema were observed in patients treated with nipocalimab-aahu. In a clinical study, infusion-related reactions were mild to moderate in severity and occurred within one hour to 2 days of administration.

The most common adverse reactions (10% or more) in patients with gMG include respiratory tract infections, peripheral edema, and muscle spasms.

There are limited data on the use of nipocalimab-aahu in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There was no evidence of direct adverse effects on fetal development following administration of nipocalimab-aahu to pregnant monkeys; however, adverse effects on the placenta were associated with fetal loss at both doses tested. The background risk of major birth defects and miscarriage for the indicated population is unknown. There is a pregnancy safety study for Imaavy. 

Nipocalimab-aahu is excreted in human colostrum and breastmilk based on limited data from an investigational study of 13 pregnant women administered nipocalimab-aahu during pregnancy where colostrum and breastmilk was assessed in the first 8 days after birth. There are insufficient data on the effect of nipocalimab-aahu in the breastfed infant. There are no data on the effect of nipocalimab on milk production.

Safety and effectiveness of nipocalimab-aahu for the treatment of gMG in pediatric patients below the age of 12 years have not been established. 

Clinical studies of nipocalimab-aahu did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger adult patients.

Generalized Myasthenia Gravis (gMG)

Myasthenia gravis is a chronic autoimmune, neuromuscular disease that is characterized by weakness and fatigue of skeletal (voluntary) muscles that worsens after periods of activity and improves after periods of rest. The voluntary muscles affected can include those that are responsible for controlling the eyes, face, mouth, throat, limbs and respiratory muscles. In some affected individuals, the condition may be limited to certain eye muscles, which is often described as “ocular myasthenia". When myasthenia gravis affects multiple muscle groups throughout the body, it is called generalized myasthenia gravis (gMG). 

In myasthenia gravis, the immune system produces anti-acetylcholine receptor (AChR) antibodies that interfere with communication between nerves and muscles, resulting in muscle weakness and fatigue. Severe attacks of weakness, such as in myasthenia gravis crisis, can cause breathing and swallowing problems that can be life-threatening.

In April 2025, the FDA approved Imaavy for the treatment of gMG in adult and pediatric patients 12 years of age and older who are AChR or MuSK antibody positive. Approval was based on the positive outcomes from the Vivacity-MG3 study in adults and a 24-week, single arm study evaluating the safety of nipocalimab in pediatric patients age 12 of age and older.

The Vivacity-Myasthenia Gravis 3 (Vivacity-MG3; NCT04951622) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial that evaluated the safety and efficacy of nipocalimab in adults with gMG who were anti-AChR or anti-MuSK antibody positive and inadequately controlled on standard-of-care (SOC) therapy. A total of 196 patients were randomized 1:1 to receive either nipocalimab (n=98) or placebo (n=98), with the primary efficacy analysis conducted in the antibody-positive population (n=153; 77 nipocalimab, 76 placebo). Patients received either nipocalimab (30 mg/kg loading dose then 15 mg/kg every 2 weeks for maintenance dosing) or placebo infusions every 2 weeks, added to standard-of-care therapy in both groups, for 24 weeks. The primary endpoint was the least-squares (LS) mean change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score, averaged over weeks 22, 23, and 24. Nipocalimab demonstrated a statistically significant improvement: LS mean change of -4.7 (SE 0.33) versus -3.3 (SE 0.34) for placebo, with a treatment difference of -1.5 (95% CI: -2.4, -0.5; p=0.002). The key secondary endpoint was the change in Quantitative Myasthenia Gravis (QMG) total score over weeks 22 and 24. Nipocalimab showed a LS mean change of -4.9 (SE 0.5) versus -2.1 (SE 0.5) for placebo, with a treatment difference of -2.8 (95% CI: -4.2, -1.4; p<0.001). The incidence of adverse events, including infections and headache, was similar between groups, and serious adverse events were numerically lower in the nipocalimab group (9% of 98 patients in the nipocalimab group and 14% of 98 patients in the placebo group, 3 of which had a fatal outcome (nipocalimab: myasthenic crisis; placebo: cardiac arrest and myocardial infarction). These results support the role of nipocalimab as a safe and effective adjunct to SOC for sustained disease control over 6 months in antibody-positive gMG (Antozzi et al., 2025). 

Trial inclusion criteria were (not all-inclusive):

• gMG as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II a/b, III a/b, or IVa/b at screening
• MG-ADL score of greater than or equal to 6 at screening and baseline

Trial exclusion criteria were (not all-inclusive):

• Any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of gMG, or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant
• MGFA Class I disease or presence of MG crisis (MGFA Class V) at screening, history of MG crisis within 1 month of screening, or fixed weakness (and/or 'burnt out' MG)
• Thymectomy within 12 months prior to screening, or thymectomy is planned during the study
• Experienced myocardial infarction, unstable ischemic heart disease, or stroke within 12 weeks of screening

Per the label, the safety and effectiveness of nipocalimab for the treatment of gMG have been established in pediatric patients 12 years of age and older. Use in pediatric patients for this indication is supported by evidence from an adequate and well-controlled trial in adults with additional pharmacokinetic and safety data in pediatric patients who are 12 years of age and older. In a 24-week, single arm study evaluating the safety of nipocalimab in 7 pediatric patients age 12 to 16 years with gMG who were AChR positive, adverse reactions were consistent with those observed in adult patients with gMG.

Longer-term safety and efficacy data are being collected in an ongoing open-label extension phase (Antozzi et al., 2025).

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Appendix

Appendix A: Myasthenia Gravis Foundation of America (MGFA) Clinical Classification

1. Class I: Any ocular muscle weakness; may have weakness of eye closure. All other muscle strength is normal.

2. Class II: Mild weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.

   1. IIa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
   2. IIb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.

3. Class III: Moderate weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.

   1. IIIa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
   2. IIIb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.

4. Class IV: Severe weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.

   1. IVa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
   2. IVb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.

5. Class V: Defined as intubation, with or without mechanical ventilation, except when employed during routine postoperative management. The use of a feeding tube without intubation places the patient in class IVb.

Source: Myasthenia Gravis Foundation of America (MGFA)

Appendix B: Myasthenia Gravis Activities of Daily Living Scale

The Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) is an 8-item patient-reported outcome measure assessing myasthenia gravis (MG) symptoms and functional activities related to activities of daily living and producing a total score ranging from 0 to 24, where higher scores indicate greater severity of symptoms. The MG-ADL is composed of items related to patients’ assessment of functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb impairment (2 items).

Source: Muppidi, et al. (2022)

Appendix C: The Myasthenia Gravis Composite

The Myasthenia Gravis Composite (MG Composite) is a 10-item tool that measures the signs and symptoms of myasthenia gravis (MG) based on physician examination and patient history. Scored items include ptosis, double vision, eye closure, talking, chewing, swallowing, breathing, neck flexion, shoulder abduction, and hip flexion. Each item is scored on an ordinal scale with four possible categories and weighted. The total score ranges from 0 to 50, with higher scores indicating more severe impairments. The MG Composite is composed of items originating from other scales (i.e., Quantitative Myasthenia Gravis [QMG], Manual Muscle Test [MMT], Myasthenia Gravis Activities of Daily Living [MG-ADL] scale).

Source: Myasthenia Gravis Rare Disease Network (MGNet)

Appendix D: The Manual Muscle Test

The MMT is a tool that evaluates the strength in 12 bilateral muscle groups and 6 ocular or axial (e.g., neck flexors) muscles, that are usually affected in MG. Each muscle is scored from 0 (normal strength) to 4 (paralysis), and the total score is the sum of each muscle, where higher scores indicate more strength (less disease severity).

Source: Barnett et al. (2018)

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References