Vivacity-MG
(2024)Objective
To evaluate the safety and efficacy of IV nipocalimab, a fully human anti-neonatal Fc receptor (FcRn) monoclonal antibody, in patients with generalized myasthenia gravis (gMG) who had inadequate response to standard-of-care therapy.
Study Summary
• TEAE incidence similar between combined nipocalimab and placebo groups (83.3% vs 78.6%)
• Infections occurred in 33.3% of nipocalimab vs 21.4% of placebo patients
• No deaths, no discontinuations due to TEAEs, and no AESIs (grade ≥3 infection or hypoalbuminemia) observed with nipocalimab
• 57/68 patients (83.8%) completed treatment through day 57
Intervention
IV nipocalimab (anti-FcRn monoclonal antibody) at 5 mg/kg Q4W, 30 mg/kg Q4W, 60 mg/kg Q2W for 8 weeks, or 60 mg/kg single dose, vs IV placebo Q2W, all added to background standard-of-care therapy.
Inclusion Criteria
Adults ≥18 years with history and clinical symptoms of gMG; positive serology for anti-AChR or anti-MuSK autoantibodies; QMG score ≥12 and MG-ADL score ≥4 despite stable SOC therapy; MGFA Class II, III, or IVa.
Study Design
Arms: Placebo Q2W vs Nipocalimab 5 mg/kg Q4W vs Nipocalimab 30 mg/kg Q4W vs Nipocalimab 60 mg/kg Q2W vs Nipocalimab 60 mg/kg single dose (combined nipocalimab n=54; placebo n=14)
Patients per Arm: Placebo n=14; combined nipocalimab n=54 (total N=68)
Outcome
• No individual nipocalimab dose significantly improved MG-ADL vs placebo
• Safety profile comparable to placebo: TEAEs 83.3% vs 78.6%; infections 33.3% vs 21.4%
• No deaths, no treatment discontinuations from TEAEs, no grade ≥3 infections or hypoalbuminemia
• 64/68 patients (94.1%) were anti-AChR positive; 4 (6%) were anti-MuSK positive
Bottom Line
In this phase 2 study, nipocalimab was generally safe, well-tolerated, and demonstrated a statistically significant dose-dependent reduction in MG-ADL at day 57 (p = 0.031) when added to standard-of-care therapy in gMG, supporting further evaluation in phase 3 trials.
Major Points
- Statistically significant dose response in MG-ADL change from baseline to day 57 (p = 0.031, linear trend test) across placebo, 5 mg/kg Q4W, 30 mg/kg Q4W, and 60 mg/kg Q2W arms
- No individual nipocalimab dose significantly improved MG-ADL vs placebo at day 57
- TEAE rates similar between combined nipocalimab (83.3%) and placebo (78.6%) groups
- Infection rates 33.3% (nipocalimab) vs 21.4% (placebo); no grade ≥3 infections or hypoalbuminemia
- No deaths and no discontinuations due to TEAEs with nipocalimab
- Supports phase 3 development of nipocalimab for gMG
Study Design
- Study Type
- Multicenter, randomized, double-blind, placebo-controlled, phase 2 study
- Randomization
- Yes
- Blinding
- Double-blind (patients, investigators, sponsor, and site personnel blinded); permuted block randomization stratified by autoantibody type (anti-AChR vs anti-MuSK) and baseline MG-ADL score (≤10, >10) for anti-AChR positive patients
- Sample Size
- 68
- Follow-up
- 8-week double-blind treatment period followed by 8-week posttreatment follow-up (4-week screening period preceding)
- Centers
- 38
- Countries
- United States, Canada, Germany, Italy, Poland, Spain, Belgium, United Kingdom
Primary Outcome
Definition: Change from baseline to day 57 in MG-ADL total score; dose response assessed by linear trend test over placebo, 5 mg/kg Q4W, 30 mg/kg Q4W, and 60 mg/kg Q2W
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| - | 0.031 (linear trend test) |
Limitations & Criticisms
- Small sample size (N=68 randomized; 14 in placebo) limits power for individual dose comparisons
- Short 8-week treatment period may not capture long-term efficacy or safety signals
- No individual nipocalimab dose significantly improved MG-ADL vs placebo — only the linear dose-response trend was significant
- Only 4 anti-MuSK positive patients enrolled, limiting inference in this subgroup
- Class I evidence designation notes nipocalimab did not significantly improve MG-ADL at any individual dose
Citation
Neurology 2024;102:e207937. doi:10.1212/WNL.0000000000207937