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IMAAVY™ (nipocalimab-aahu)

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IMAAVY - Long-term Phase 3 Safety and Efficacy in Patients with Generalized Myasthenia Gravis

Last Updated: 08/27/2025

SUMMARY

  • In an open-label extension (OLE) phase of a 24-week, phase 3, randomized, double-blind (DB), placebo (PBO)-controlled trial in adult patients with generalized myasthenia gravis (gMG)1,2:
    • The mean standard error (SE) from DB baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score was -5.64 (0.621) in the IMAAVY → IMAAVY + standard of care (SOC) group and -6.01 (0.503) in the PBO → IMAAVY + SOC group (P<0.001).1 
    • No cases of unexpected adverse events (AEs) were reported during the OLE phase.3 
  • In separate analyses of the PBO→IMAAVY + SOC group and IMAAVY→IMAAVY + SOC group:
    • A total of 63.3% of patients in the PBO→IMAAVY + SOC group and 84.6% of patients in the IMAAVY→IMAAVY + SOC group achieved meaningful clinical improvement (MCI) in the MG-ADL score at OLE week 24.4,5
    • A total of 44.3% of patients in the PBO→IMAAVY + SOC group and 26.9% of patients in the IMAAVY→IMAAVY + SOC group achieved minimal symptom expression (MSE) in the MG-ADL score at OLE week 24.4,5

Clinical data

VIVACITY-MG3

Antozzi et al (2025)1,2 evaluated the efficacy and safety of IMAAVY in adults with gMG in a phase 3, randomized, multicenter, DB, PBO-controlled study.

Study Design/Methods

  • Patients (≥18 years of age) with anti- acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), or low-density lipoprotein receptor-related protein 4 (LRP4) antibody positive or seronegative (in all countries except France) gMG (Myasthenia Gravis Foundation of America [MGFA] class IIa-IVb) were included in the study.2,6
    • The safety analysis population included all randomized patients who received ≥1 dose (partial or complete) of any study treatment in the DB phase or of IMAAVY in the OLE phase.2,3 
    • The primary efficacy analysis population included all patients from the safety analysis dataset who were antibody-positive for AChR, MuSK, or LRP4, confirmed prior to randomization.2 
  • The study consisted of a ≤4-week screening phase, followed by a 24-week, DB, PBO-controlled treatment phase, a variable-duration OLE phase, and safety follow-up at 8 weeks after the last infusion.2,7 
    • Patients who withdrew or discontinued after receiving any amount of the study intervention were required to complete a safety follow-up assessment at 8 weeks after the last dose.7 
  • Eligible patients were randomized (1:1) to receive a loading dose of intravenous (IV) IMAAVY 30 mg/kg at week 0 followed by 15 mg/kg every 2 weeks (Q2W) or matching PBO through week 24 in addition to SOC therapy.2 
  • Patients entering the OLE phase continued to receive IMAAVY 15 mg/kg Q2W in addition to SOC.1,3 
  • The primary efficacy endpoint was the average change from baseline in the MG-ADL total score over weeks 22, 23, and 24.2 
  • A key secondary endpoint was the average change in the Quantitative Myasthenia Gravis (QMG) score over weeks 22 and 24.2 

Results

  • Overall, 176 patients were included in the OLE safety analysis set.3 
  • Of those patients, 137 patients were included in the primary efficacy analysis set (patients who were antibody-positive only), with 71 patients randomized to IMAAVY and 66 randomized to PBO. See Table: Baseline Demographics and Characteristics (Seropositive Population).

Baseline Demographics and Characteristics (Seropositive Population)1 

IMAAVY → IMAAVY + SOC
Placebo → IMAAVY + SOC
Analysis set: seropositive efficacya, n
71
66
Mean age, years (range)
51.1 (20-81)
51.6 (20-81)
Female, n (%)
46 (64.8)
38 (57.6)
Baseline MG-ADL total score, mean (SD)
9.3 (2.75)
9.0 (1.98)
Baseline QMG total score, mean (SD)
15.2 (4.85)
15.6 (4.90)b
Anti-AChR+/anti-MuSK+/anti-LRP4+, n
59/10/2
61/4/1
Abbreviations: AChR, acetylcholine receptor; DB, double-blind; LRP4, low-density lipoprotein receptor-related protein 4; MG-ADL, Myasthenia Gravis Activities of Daily Living; MuSK, muscle-specific tyrosine kinase; OLE, open-label extension; QMG, Quantitative Myasthenia Gravis; SD, standard deviation; SOC, standard of care.
aAll randomized seropositive patients who received ≥1 dose of study intervention in the DB phase or all seropositive patients who received ≥1 dose of IMAAVY in the OLE phase.
bn=67
Efficacy
  • A total of 137 patients with antibody-positive gMG were treated with IMAAVY in the OLE phase with a follow-up duration of over 62 weeks.1
  • At week 60, the mean (SE) change from DB baseline in the MG-ADL total score in the IMAAVY → IMAAVY + SOC group was -5.64 (0.621) and -6.01 (0.503) in the PBO → IMAAVY + SOC group (P<0.001). See Figure: Mean Change in the MG-ADL Total Score from DB Baseline (Seropositive Population).

Mean Change in the MG-ADL Total Score from DB Baseline (Seropositive Population)1 

Note: P-value for comparison of MG-ADL total score change from baseline significantly different from zero using a 1-sample t-test.
Abbreviations: DB, double-blind; MG-ADL, Myasthenia Gravis Activities of Daily Living; OL, open-label; PBO, placebo; SE, standard error; W, week.

Mean Change in the QMG Total Score from DB Baseline (Seropositive Population)1

Note: P-value for comparison of QMG total score change from baseline significantly different from zero using a 1-sample t-test.
Abbreviations: DB, double-blind; OL, open-label; PBO, placebo; QMG, Quantitative Myasthenia Gravis; SE, standard error; W, week.

Safety

Safety and Tolerability (Exposure Adjusted Incidence Rate)3 
OLE All IMAAVY
Analysis set, n
176
Average follow-up duration, weeks
70.53
PYa
237.9
Events/PYa
Events, n
Patients, nb
All AEs
5.59
1331
159
Serious AEs
0.31
74
46
Fatal AEs
0.02
4
4
Treatment discontinuation due to AEsc
0.05
13
13
Infections and infestations
1.39
330
125
Infusion-related reactionsd
0.07
17
10
Adjudicated MACE, fatal
0.01
3
3
Adjudicated MACE, not fatal
0.03
7
1
Abbreviations: AE, adverse event; DB, double-blind; eCRF, electronic case report form; MACE, major adverse cardiac events; OLE, open-label extension; PY, patient years.
aPY of observation is calculated as the total duration of follow-up in days/365.25.
bPatients with ≥1 AE are shown.
cPermanent discontinuation of treatment. Treatment discontinuation for an AE with onset in the DB (or OLE) phase occurred in the DB (or OLE) phase.
dIndicated as infusion reaction by investigator on eCRF and relationship to study intervention=“Related”.

AEs by Preferred Term (Exposure Adjusted Incidence Rate)3 
OLE All IMAAVY (n=176)
PYa
237.9
Events/PYa
Events, n
Patients, nb
Upper respiratory tract infection
0.21
50
39
Nasopharyngitis
0.18
44
33
COVID-19
0.11
25
23
Urinary tract infection
0.12
28
19
Back pain
0.09
22
18
Muscle spasms
0.08
19
12
Pain in extremity
0.05
11
10
Arthralgia
0.08
18
13
Myasthenia gravis
0.20
48
31
Headache
0.21
50
29
Dizziness
0.02
5
4
Peripheral edema
0.04
10
9
Pyrexia
0.05
11
10
Diarrhea
0.08
20
20
Nausea
0.04
10
8
Cough
0.04
10
9
Rash
0.02
5
4
Anemia
0.03
7
7
Insomnia
0.02
4
4
Abbreviations: AE, adverse event; COVID-19, coronavirus disease 2019; OLE, open-label extension; PY, patient years.
aPY of observation is calculated as the total duration of follow-up in days/365.25.
bPatients with ≥1 AE are shown. AEs listed where system organ class event rate (number of events/PY) is ≥0.1 or preferred term event rate (number of events/PY) is ≥0 in either treatment group.
Pharmacodynamics

Total IgG Reduction from Baseline (Seropositive Population)1 

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Abbreviations: DB, double-blind; IgG, immunoglobulin G; OL, open-label; PBO, placebo; SE, standard error; W, week.

Claeys et al (2025)4 conducted an additional analysis of VIVACITY-MG3 to evaluate the efficacy of IMAAVY + SOC in the OLE phase in patients who transitioned from PBO + SOC in the DB phase.

Study Design/Methods

  • Study assessments included the following:
    • Proportion of patients achieving MCI, defined as a ≥2-point improvement in the MG-ADL total score from OLE baseline
    • Proportion of patients achieving MSE, defined as an MG-ADL score of 0 or 1
    • Proportion of patients with sustained MCI and MSE for ≥8 weeks
    • Percentage of time spent in MCI, defined as percentage of time with improvement calculated as the cumulative days of improvement divided by the number of days in OLE up to week 24
    • Percentage of time spent in MSE, defined as percentage of time with improvement calculated as the cumulative days of MSE divided by the number of days in OLE up to week 24

Results

  • A total of 88 patients were included in the OLE efficacy analysis set.
  • Data were collected through OLE week 24, with a cutoff date of August 23, 2024.
  • The mean (standard deviation [SD]) duration of IMAAVY exposure was 36.1 (23.05) weeks.
    • Of the 88 patients included, 68.2% and 29.5% received IMAAVY for ≥6 months and ≥12 months, respectively.
Proportion of Patients Achieving and Sustaining MCI
  • A total of 63.3% of patients achieved MCI in the MG-ADL score through OLE week 24 (n=60).
  • The earliest onset of MCI occurred at a mean (SD) of 5.1 (4.99) weeks.
  • Sustained MCI for ≥8 weeks was reported in 51.1% of patients.
  • The mean (SD) percentage of time spent in MCI during the OLE phase was 40.7% (38.7).
    • The percentage of study time spent in MCI was ≥50% and ≥75% in 39 (44.3%) and 30 (34.1%) patients, respectively.
Proportion of Patients Achieving and Sustaining MSE
  • A total of 44.3% of patients achieved MSE in the MG-ADL score through OLE week 24 (n=88).
  • The earliest onset of MSE occurred at a mean (SD) of 7.4 (7.37) weeks.
  • Sustained MSE for ≥8 weeks was reported in 22.7% of patients.
  • The mean (SD) percentage of time spent in MSE during the OLE phase was 17.6% (31.06).
    • The percentage of study time spent in MSE was ≥50% in 15 (17%) patients.

Silvestri et al (2025)5 conducted an additional analysis of VIVACITY-MG3 to evaluate the long-term efficacy of IMAAVY + SOC in the OLE phase in patients who transitioned from IMAAVY + SOC in the DB phase.

Study Design/Methods

  • Study assessments included the following:
    • Proportion of patients achieving MCI, defined as a ≥2-point improvement in the MG-ADL total score from DB baseline
    • Proportion of patients achieving MSE, defined as an MG-ADL score of 0 or 1
    • Proportion of patients with sustained MCI and MSE for ≥8 weeks
    • Percentage of time spent in MCI, defined as cumulative days of improvement divided by the number of days in the study up to OLE week 24 (ie, week 48 of IMAAVY treatment)
      • The number of days in the study up to OLE week 24 was calculated as the OLE week 24 date (or the early termination date if earlier) minus the DB baseline date.
    • Percentage of time spent in MSE, defined as percentage of time with improvement calculated as cumulative days of MSE divided by the number of days in the study up to OLE week 24.
      • The number of days in the study up to OLE week 24 was calculated as the OLE week 24 date (or the early termination date if earlier) minus the DB baseline date.

Results

  • A total of 98 patients from the IMAAVY + SOC arm of the DB phase transitioned to the IMAAVY + SOC arm of the OLE phase.
  • Data were collected through OLE week 24, with a cutoff date of August 23, 2024.
  • The mean (SD) duration of IMAAVY exposure was 59.9 (24.14) weeks (n=88).
    • Of 88 patients, 97.7% and 59.1% received IMAAVY for ≥6 months and ≥12 months, respectively.
Proportion of Patients Achieving and Sustaining MCI
  • A total of 84.6% of patients achieved MCI in the MG-ADL score through OLE week 24 (n=52).
  • The earliest onset of MCI occurred at a mean (SD) of 4.0 (5.95) weeks.
  • Sustained MCI for ≥8 weeks was reported in 77.6% of patients.
  • The mean (SD) percentage of time spent in MCI through week 48 was 71.6% (34.14).
    • The percentage of study time spent in MCI was ≥50% and ≥75% in 65 (73.9%) and 59 (67.0%) patients, respectively.
Proportion of Patients Achieving and Sustaining MSE
  • A total of 26.9% of patients achieved MSE in the MG-ADL score through OLE week 24 (n=52).
  • The earliest onset of MSE occurred at a mean (SD) of 14.5 (15.12) weeks.
  • Sustained MSE for ≥8 weeks was reported in 23.5% of patients.
  • The mean (SD) percentage of time spent in MSE through OLE week 24 was 15.9% (30.21).
    • The percentage of study time spent in MSE was ≥50% and ≥75% in 15 (17.0%) and 11 (12.5%) patients, respectively.

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 08 July 2025.

 

References

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1 Antozzi C, Vu T, Ramchandren S, et al. Long-term safety and efficacy of nipocalimab in generalized myasthenia gravis: VIVACITY-MG3 open-label extension phase results. Poster presented at: 77th Annual Meeting of the American Academy of Neurology (AAN); April 5-9, 2025; San Diego, CA.  
2 Antozzi C, Vu T, Ramchandren S, et al. Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2025;24(2):105-116.  
3 Katzberg H, Ait-Tihyaty M, Turkoz I, et al. Safety profile of nipocalimab, a new neonatal fragment crystallizable receptor blocker in the phase 3 Vivacity study. Poster presented at: 15th Myasthenia Gravis Foundation of America (MGFA) International Conference; May 13-15, 2025; The Hague, The Netherlands.  
4 Claeys KG, Ait-Tihyaty M, Gandhi K, et al. Efficacy of nipocalimab in open-label extension in patients transitioned from placebo: results from Vivacity-MG3 trial. Oral Presentation presented at: 11th Congress of the European Academy of Neurology (EAN); June 21-24, 2025; Helsinki, Finland.  
5 Silvestri NJ, Ait-Tihyaty M, Gandhi K, et al. Analysis of long-term efficacy of nipocalimab in myasthenia gravis: open-label extension of the Vivacity-MG3 trial. Oral Presentation presented at: 11th Congress of the European Academy of Neurology (EAN); June 21-24, 2025; Helsinki, Finland.  
6 Vu T, Antozzi C, Ramchandren S, et al. Efficacy and safety of nipocalimab in patients with generalized myasthenia gravis - top line results from the double-blind, placebo-controlled, randomized phase 3 Vivacity-MG3 study. Poster presented at: American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting; October 15-18, 2024; Savannah, GA.  
7 Antozzi C, Vu T, Ramchandren S, et al. Supplement to: Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2025;24(2):105-116.