Imaavy Drug Information
Generic name: NIPOCALIMAB-AAHU
Uses of Imaavy
Generalized Myasthenia
Gravis (gMG) 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.
Warm Autoimmune Hemolytic
Anemia (wAIHA) IMAAVY is indicated for the treatment of warm autoimmune hemolytic anemia (wAIHA) in adult and pediatric patients 12 years of age and older currently or previously treated with corticosteroids.
Dosage & Administration of Imaavy
Recommended Vaccination Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of IMAAVY. Because IMAAVY causes transient reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with IMAAVY.
Recommended Dosage for gMG Dilute
IMAAVY prior to administration. Administer via intravenous infusion only. Table 1: gMG Recommended Dose Regimen Initial dosage Maintenance dosage 30 mg/kg administered once via intravenous infusion over at least 30 minutes.
Continue the maintenance dose every two weeks thereafter.
Recommended Dosage for wAIHA Dilute
IMAAVY prior to administration. Table 2: wAIHA Recommended Dose Regimen Initial dosage Subsequent dosage 30 mg/kg administered once via intravenous infusion over at least 30 minutes. Continue the subsequent dose every four weeks thereafter.
Missed Doses If a scheduled infusion is missed, administer the dose of IMAAVY as soon as possible. Resume dosing, maintaining the treatment interval.
Preparation and Administration Instructions Prior to administration, dilute IMAAVY single-dose vials with only 0.9% Sodium Chloride Injection using the instructions below. For patients who weigh 40 kg or more, the total volume to be administered is 250 mL; for patients who are 12 years or older and weigh less than 40 kg, the total volume to be administered is 100 mL (see Preparation ). Preparation Prepare the solution for infusion using aseptic technique as follows: Calculate the dosage (mg), total drug volume (mL) of IMAAVY solution required, and the number of IMAAVY vials needed, based on the patient's current weight.
Each single-dose vial of IMAAVY is at a concentration of 185 mg/mL. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Check that the solution in each vial is colorless to slightly brownish, clear to slightly opalescent, and free of visible particles.
Do not use if visible particles are present or if the solution is discolored (other than colorless to slightly brownish). Gently withdraw the calculated volume of IMAAVY from the vial(s). Discard any unused portion of the vials.
Dilute total volume withdrawn of IMAAVY by adding to an infusion container containing 0.9% Sodium Chloride Injection to a final volume of: 250 mL for patients who weigh 40 kg or more, or 100 mL for patients who weigh less than 40 kg. Only use infusion containers made of polyolefin, polypropylene, or polyvinylchloride. Gently invert the infusion container at least 10 times to mix the solution.
Do not shake. Verify that a uniform solution has been achieved by visual inspection. Do not use if particulate matter or discoloration is present.
Storage Conditions of the Diluted Solution Administer the diluted IMAAVY solution immediately after preparation. If the diluted IMAAVY solution is not used immediately: Protect from light. Do not freeze.
After preparation or removal from the refrigerator, use or discard the IMAAVY diluted solution within 12 hours, including infusion time. Administration If the diluted solution is refrigerated prior to administration, allow to warm to room temperature. Do not use external heat sources to warm IMAAVY.
Administer the diluted solution by intravenous infusion only using an infusion set with an in-line or add-on, sterile, non-pyrogenic, low protein-binding filter made of polyethersulfone or polysulfone (pore size 0.2 micrometer or less). Administration sets must be made of either polybutadiene, polyethylene, polyurethane, polypropylene, or polyvinylchloride. Do not infuse IMAAVY concomitantly in the same intravenous line with other agents.
Administer IMAAVY infusion intravenously over at least 30 minutes for the initial dose and at least 15 minutes for subsequent doses. If an adverse reaction occurs during administration of IMAAVY, the infusion may be slowed or stopped at the discretion of the healthcare professional. Monitor the patient for 30 minutes after each infusion for signs or symptoms of an infusion-related or hypersensitivity reaction.
| Initial dosage | Maintenance dosage |
|---|---|
| 30 mg/kg administered once via intravenous infusion over at least 30 minutes. | Two weeks after the initial dose administer a maintenance dose of 15 mg/kg via intravenous infusion over at least 15 minutes. Continue the maintenance dose every two weeks thereafter. |
| Initial dosage | Subsequent dosage |
|---|---|
| 30 mg/kg administered once via intravenous infusion over at least 30 minutes. | Four weeks after the initial dose administer a subsequent dose of 30 mg/kg via intravenous infusion over at least 15 minutes. Continue the subsequent dose every four weeks thereafter. |
Side Effects of Imaavy
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults with gMG In gMG Study 1 and its extension study, the safety of IMAAVY was evaluated in 186 patients with gMG who received at least one dose of IMAAVY. The mean age at study entry was 53 years (range 20 to 81).
Adverse reactions reported in gMG Study 1 in at least 5% of patients treated with IMAAVY and more frequently than placebo, are summarized in Table 3. The most common adverse reactions (reported in at least 10% of patients treated with IMAAVY) were respiratory tract infection, peripheral edema, and muscle spasms. Two (1%) cases of infections (cellulitis and urinary tract infection) led to discontinuation of IMAAVY.
One patient experienced hypersensitivity reaction (urticaria) that required discontinuation of IMAAVY. No patients experienced infusion-related reaction that required discontinuation of IMAAVY. Five percent of patients treated with IMAAVY had decreases from normal to low of fasting HDL cholesterol (<40 mg/dL).
Pediatric Patients 12 Years of Age and Older with gMG In a 24-week, single arm study (gMG Study 2), evaluating the safety of IMAAVY 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. Adults with wAIHA The safety of IMAAVY in patients with wAIHA was evaluated in 113 adult patients with wAIHA who received at least one dose of IMAAVY. The median duration of treatment was 44 weeks.
In the double-blind phase of the wAIHA Study, 78 patients received IMAAVY across the dose regimens evaluated in the study. Adverse reactions that occurred in the wAIHA Study in at least 5% of patients treated with IMAAVY are summarized in Table 4. Three (2.7%) cases of infections (pneumonia, salmonella sepsis and spontaneous bacterial peritonitis) led to discontinuation of IMAAVY.
Hypersensitivity Reactions In the wAIHA Study and its extension study, out of 113 patients treated with IMAAVY, 9 (8%) patients experienced hypersensitivity reactions. Infusion-Related Reactions In the wAIHA Study and its extension study, out of 113 patients treated with IMAAVY, 12 (11%) patients experienced infusion-related reactions. One patient in the wAIHA Study discontinued IMAAVY due to an infusion-related reaction (back pain).
Laboratory Findings Lipids In the double-blind phase of the wAIHA Study (N=78), 2.3% of patients treated with IMAAVY had elevations from normal to high of fasting total cholesterol ( ≥ 240 mg/dL) and LDL cholesterol remained <160 mg/dL for all patients at Week 24. Of the patients treated with IMAAVY, 12% had fasting HDL cholesterol of <40 mg/dL.
| Adverse Reaction | IMAAVY N=98 % | Placebo N=98 % |
|---|---|---|
| Includes the following reported in patients treated with IMAAVY: | ||
| Infection | ||
| Respiratory tract infection COVID-19 (and other related terms), pneumonia, bronchitis, pneumonia bacteria | 18 | 13 |
| Urinary tract infection other related terms | 6 | 3 |
| Herpes zoster and Herpes simplex | 6 | 2 |
| Oral infection glossitis, oral candidiasis, pericoronitis, pulpitis dental, tooth abscess, tooth infection | 5 | 3 |
| Peripheral edema | 12 | 2 |
| Muscle spasm | 12 | 3 |
| Hypersensitivity reaction angioedema, dermatitis atopic, eczema, gingival swelling, rash (and other related terms), urticaria | 8 | 7 |
| Abdominal pain | 8 | 3 |
| Back pain | 8 | 5 |
| Pyrexia | 7 | 1 |
| Diarrhea | 7 | 3 |
| Cough | 7 | 3 |
| Anemia | 6 | 4 |
| Dizziness | 5 | 1 |
| Nausea | 5 | 2 |
| Hypertension | 5 | 2 |
| Insomnia | 5 | 2 |
| Adverse Reaction | IMAAVY N=78 % | Placebo N=39 % |
|---|---|---|
| Peripheral edema Includes Edema peripheral, Edema and Generalized edema. | 12 | 2.6 |
| Diarrhea | 12 | 8 |
| Pyrexia | 10 | 2.6 |
| Dizziness | 9 | 8 |
| Infection | ||
| Urinary tract infection Includes Urinary tract infection, Pyelonephritis and Urinary tract infection bacterial. | 9 | 5 |
| Headache | 6 | 5 |
Warnings & Cautions for Imaavy
Infections IMAAVY may increase the risk of infection. Delay IMAAVY administration in patients with an active infection until the infection is resolved. During treatment with IMAAVY, monitor for clinical signs and symptoms of infection.
If serious infection occurs, administer appropriate treatment and consider withholding IMAAVY until the infection has resolved. Latent Viral Infections Patients treated with IMAAVY may be at an increased risk of activation of latent viral infections, such as herpes zoster. In the extension period of gMG Study 1, there were 2 patients with serious adverse reactions related to Epstein-Barr virus (EBV) infection, and 1 of these patients had fatal complications.
Patients who screened positive for hepatitis were excluded from gMG Study 1. Follow standard vaccination guidelines. Immunization The safety of immunization with live vaccines and the immune response to vaccination during treatment with IMAAVY are unknown.
Because IMAAVY causes a reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with IMAAVY. Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of treatment with IMAAVY.
Hypersensitivity Reactions
In clinical trials, hypersensitivity reactions, including angioedema, anaphylaxis, rash, urticaria, and eczema were observed in patients treated with IMAAVY. In gMG Study 1 and the wAIHA Study, hypersensitivity reactions were mild or moderate. In gMG Study 1, all hypersensitivity reactions occurred within one hour to 2 weeks of administration.
In the wAIHA Study, 76% of hypersensitivity reactions occurred within 2 weeks of administration. In gMG Study 1, one patient experienced a hypersensitivity reaction (urticaria) that led to treatment discontinuation. Management of hypersensitivity reactions depends on the type and severity of the reaction.
If a hypersensitivity reaction occurs during administration, discontinue IMAAVY infusion and institute appropriate supportive measures if needed. IMAAVY is contraindicated in patients with a history of serious hypersensitivity to nipocalimab-aahu or any of the excipients of IMAAVY.
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 IMAAVY. In gMG Study 1 and the wAIHA Study, infusion-related reactions were mild to moderate in severity. In gMG Study 1, all infusion-related reactions occurred within one hour to 2 days of administration.
In the wAIHA Study, 89% of infusion-related reactions occurred within 2 days of administration. Monitor patients during treatment with IMAAVY and for 30 minutes after each infusion. If a severe infusion-related reaction occurs, discontinue IMAAVY infusion and initiate appropriate therapy.
Consider the risks and benefits of readministering IMAAVY following a severe infusion-related reaction. If a mild to moderate infusion-related reaction occurs, patients may be rechallenged with close clinical observation, slower infusion rates, and pre-medication.
Drug Interactions with Imaavy
Effect of IMAAVY on Other Drugs
Concomitant use of IMAAVY with medications that bind to the human neonatal Fc receptor (FcRn) (e.g., immunoglobulin products, monoclonal antibodies, or antibody derivates containing the human Fc domain of the IgG subclass) may lower systemic exposures and reduce effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. When concomitant long-term use of such medications is essential for patient care, consider discontinuing IMAAVY, and using alternative therapies.
Pregnancy Safety for Imaavy
Pregnancy Risk Summary There are limited data on the use of IMAAVY 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 (see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is respectively. There is a pregnancy safety study for IMAAVY.
If IMAAVY is administered during pregnancy, or if a patient becomes pregnant while receiving IMAAVY, healthcare providers should report IMAAVY exposure by contacting Janssen at 1-800-526-7736 or www.IMAAVY.com Clinical Considerations Fetal/Neonatal Adverse Reactions Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Because IMAAVY reduces maternal serum IgG concentration and impedes placental IgG transfer to the fetus, passive immunity in the infant may be reduced for 6 months or more; therefore: Monitor for the development of serious infection. Effectiveness of vaccines may be reduced.
Consider the risks and benefits prior to administering live vaccines to infants exposed to IMAAVY in utero. Data Animal Data Intravenous administration of nipocalimab-aahu (0, 100, or 300 mg/kg) to pregnant monkeys weekly from the end of organogenesis (gestation day 45) through parturition resulted in placental ischemia, associated with fetal loss and decreased levels of immunoglobulin (IgG) in the offspring at both doses tested. IgG levels in offspring returned to normal levels and no adverse effects on immune function were evident by 6 months after birth.
Mean systemic exposures achieved at the doses tested were 5- and 24-times the population PK model simulated mean steady state exposure at the recommended human maintenance dose for gMG (15 mg/kg) and 5.5- and 28-times the population PK model simulated mean steady state exposure at the recommended human maintenance dose for wAIHA (30 mg/kg) on an AUC basis.
Pediatric Use of Imaavy
Pediatric Use gMG The safety and effectiveness of IMAAVY for the treatment of gMG have been established in pediatric patients 12 years of age and older. Use of IMAAVY 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. Safety and effectiveness of IMAAVY for the treatment of wAIHA in pediatric patients below the age of 12 years have not been established.
Contraindications for Imaavy
IMAAVY is contraindicated in patients with a history of serious hypersensitivity reaction to nipocalimab-aahu or any of the excipients in IMAAVY. Reactions have included anaphylaxis and angioedema.
Clinical Studies of Imaavy
Adults with gMG
The efficacy of IMAAVY for the treatment of gMG in adults who are anti-AChR or anti-MuSK antibody positive was established in a 24-week, multicenter, randomized, double-blind, placebo-controlled study (gMG Study 1; NCT04951622). Patients were treated with IMAAVY with the recommended dosage regimen. gMG Study 1 enrolled patients with gMG who met the following criteria: Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to IV Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score of at least 6 On stable dose of standard of care MG therapy prior to baseline that included acetylcholinesterase (AChE) inhibitors, steroids or non-steroidal immunosuppressive therapies (NSISTs), either in combination or alone. In gMG Study 1, a total of 196 patients were randomized 1:1 to receive IMAAVY (n=98) or placebo (n=98).
Baseline characteristics were similar between treatment groups. At baseline, median MG-ADL total score was 9, and median Quantitative Myasthenia Gravis (QMG) total score was 15. Eighty-eight percent (n=134) of patients were positive for AChR antibodies and 10% (n=16) were positive for MuSK antibodies.
At baseline, in each group, 85% of patients received AChE inhibitors, 66% of patients received steroids, and 54% of patients received NSISTs at stable doses. The efficacy of IMAAVY was measured using the MG-ADL scale, which assesses the impact of gMG on daily functions of 8 signs and symptoms that are typically affected in gMG. 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. The primary efficacy endpoint was the comparison of the mean change from baseline to Weeks 22, 23, and 24 between treatment groups in the MG-ADL total score. A statistically significant difference favoring IMAAVY was observed in MG-ADL total score change from baseline (p=0.002; see Table 5 and Figure 1 ).
The efficacy of IMAAVY was also measured using the QMG total score, which is a 13-item categorial grading system that assesses muscle weakness. Each item is assessed on a 4 -point scale, where a score of 0 represents no weakness, and a score of 3 represents severe weakness. A total possible score ranges from 0 to 39, where higher scores indicate more severe impairment.
A statistically significant difference favoring IMAAVY was observed in the QMG total score change from baseline (p<0.001; see Table 5 ). The results are presented shown in Table 5. In addition, patients had a hemoglobin level <10 g/dL and evidence of hemolysis and positive monospecific direct antiglobulin test (DAT).
Efficacy was established based on a randomized comparison of IMAAVY 30 mg/kg intravenously every 4 weeks (n=38) and placebo (n=39) for a double-blind period of 24 weeks. Stable concomitant wAIHA therapy was allowed during the study. Demographics and baseline disease characteristics for all randomized patients were similar between treatment groups.
Baseline disease characteristics are presented in Table 6. Table 6: Baseline Disease Characteristics of Patients in the wAIHA Study 0 0 Efficacy was based on the proportion of patients who achieved a durable hemoglobin response, defined as a hemoglobin level of ≥10 g/dL and an increase from baseline of ≥2 g/dL for at least three consecutive visits (with a minimum duration of 28 days, where criteria was met starting by Week 16 of the double-blind period), without the need of rescue therapy. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) total score was included in this study.
Efficacy results from the wAIHA Study for the recommended dose of IMAAVY 30 mg/kg every 4 weeks are shown in Table 7. Table 7: Efficacy Results for the wAIHA Study The least squares (LS) mean change in FACIT-Fatigue score from baseline to Week 24 in patients treated with IMAAVY 30 mg/kg IV every 4 weeks was LS mean difference compared to in the placebo group. Figure 3 shows the mean change from baseline in hemoglobin values by visit through Week 24. IMAAVY dose; SE=Standard Error At or after Week 16, all patients had the opportunity to discontinue in the double-blind phase and crossover to IMAAVY if they were not meeting the protocol-defined criteria.
| Efficacy Endpoints | IMAAVY N = 77 LS Mean (SE) | Placebo N = 76 LS Mean (SE) | IMAAVY Change Relative to Placebo LS Mean Difference (95% CI) | p-value |
|---|---|---|---|---|
| Key: CI=confidence interval; MG-ADL = Myasthenia Gravis – Activities of Daily Living; QMG = Quantitative Myasthenia Gravis; LS mean = Least squares mean; SE = standard error | ||||
| Primary Endpoint | ||||
| MG-ADL Total Score Mean change from baseline over weeks 22, 23, and 24 | -4.7 (0.33) | -3.3 (0.34) | -1.5 (-2.4, -0.5) | 0.002 |
| Secondary Endpoint | ||||
| QMG | ||||
| Total Score Mean change from baseline over weeks 22 and 24 | -4.9 (0.5) | -2.1 (0.5) | -2.8 (-4.2, -1.4) | <0.001 |
| Parameter | IMAAVY 30 mg/kg every 4 weeks | Placebo |
|---|---|---|
| N | 38 | 39 |
| wAIHA Type | ||
| Primary wAIHA (%) | 92.1 | 82.1 |
| Monospecific Direct Antiglobulin Test (DAT) DAT screening results are missing for two patients in the IMAAVY 30 mg/kg IV every 4 weeks group and one patient in the placebo group due to an operational issue. All three patients met the inclusion criteria and were eligible to enroll in the study. | ||
| Only IgG positive (%) | 41.7 | 63.2 |
| IgG and C3d positive (%) | 58.3 | 36.8 |
| Baseline Hemoglobin (g/dL) | ||
| Median (range) | 9.3 (5; 12) | 9.1 (5; 12) |
| Baseline FACIT-Fatigue total score Fatigue-related symptoms and impacts were assessed using a patient reported outcome instrument, FACIT-Fatigue (score range from 0 to 52 with higher scores indicating less fatigue). | ||
| Median (range) | 36.0 (14; 52) | 32.0 (8; 49) |
| Concomitant corticosteroids and/or immunosuppressants | ||
| Corticosteroids Alone or in combination with the other treatment. (%) | 89.5 | 87.2 |
| Immunosuppressants, Immunosuppressants included azathioprine, mycophenolate mofetil/mycophenolic acid, methotrexate, cyclosporine, tacrolimus, danazol, and cyclophosphamide. (%) | 23.7 | 25.6 |
| Corticosteroids and immunosuppressants (%) | 18.4 | 20.5 |
| Previous Treatment for wAIHA | ||
| Corticosteroid use only (%) | 47.4 | 59.0 |
| Rituximab (%) | 42.1 | 48.7 |
| Immunosuppressant use only (%) | 0 | 0 |
| IMAAVY 30 mg/kg every 4 weeks | Placebo | |
|---|---|---|
| Key: CI = Confidence Interval | ||
| N | 38 | 39 |
| Proportion of patients with durable hemoglobin response Durable hemoglobin response is defined as a hemoglobin level of ≥10 g/dL and an increase from baseline of ≥2 g/dL for at least three consecutive visits (with a minimum duration of 28 days, where criteria were met starting by Week 16 of the double-blind period)., Patients were considered non-responders following discontinuation or if rescue therapy was received. | 9 (23.7%) | 3 (7.7%) |
| Difference in proportions (95% CI) | 16.0 (0.1, 31.9) | |
| One-sided p-value The one-sided p-values use an alpha level of 0.02499., Statistically significant based on equal weight multiple comparison testing procedure. | 0.015 | |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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