ADAPT+
(2024)Objective
To assess the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis in an open-label extension of the phase 3 ADAPT study
Study Summary
• Safety profile consistent over up to 17 cycles with 217.6 participant-years of exposure; 84.8% had ≥1 TEAE
• Mean annualized cycles was 4.7/year; 37% had ≥9 weeks between cycles indicating sustained benefit
Intervention
Efgartigimod 10 mg/kg IV, four weekly infusions per cycle, subsequent cycles individualized based on clinical evaluation (minimum 4 weeks between cycles)
Inclusion Criteria
Patients who completed ADAPT or were eligible for treatment cycle but could not complete by week 26 of ADAPT; on stable dose of ≥1 MG medication
Study Design
Arms: Open-label efgartigimod (single arm)
Patients per Arm: 145 received ≥1 dose (111 AChR-Ab+, 34 AChR-Ab-)
Outcome
• Mean IgG reduction: 55.9% (AChR-Ab+), 60.3% (AChR-Ab-)
• SAEs in 23.4%; 5 deaths (none treatment-related)
Bottom Line
In this open-label extension with up to 217.6 participant-years of exposure and up to 17 treatment cycles, efgartigimod demonstrated consistent long-term safety and tolerability with no new safety signals. More than 90% of AChR-Ab+ participants achieved clinically meaningful improvement in MG-ADL across the first 10 treatment cycles, with rapid onset (as early as week 1), reproducible efficacy, and similar improvements in AChR-Ab- participants. An individualized dosing approach averaging 4.7 cycles per year was effective, with 37% of patients able to extend treatment intervals to ≥9 weeks between cycles.
Major Points
- Open-label extension of pivotal ADAPT study; 151 rolled over, 145 received ≥1 dose of efgartigimod
- Mean study duration 548 days; up to 17 treatment cycles; 217.6 participant-years of exposure
- Safety profile consistent with ADAPT: 84.8% had ≥1 TEAE; most common were headache (24.8%), COVID-19 (15.2%), nasopharyngitis (13.8%)
- No increase in AE frequency with subsequent cycles
- 5 deaths occurred (none considered treatment-related): acute MI, lung carcinoma, MG crisis with E. coli pneumonia, unwitnessed death with coronary atherosclerosis, septic shock from COVID-19
- >90% of AChR-Ab+ participants achieved CMI (≥2-point MG-ADL improvement) at any time point in first 10 cycles
- 69.4%-91.3% of AChR-Ab+ participants achieved CMI in QMG (≥3-point improvement) across 7 measured cycles
- Mean IgG reduction 55.9% in AChR-Ab+ and 60.3% in AChR-Ab- participants; similar reductions with each cycle
- Mean annualized cycles: 4.7/year (median 5.0, range 0.5-7.6); 37% had ≥9 weeks between cycles
- Improvements in AChR-Ab- participants similar to AChR-Ab+ participants
Study Design
- Study Type
- Open-label, single-arm, multicenter, up to 3-year extension study
- Randomization
- No
- Blinding
- Open-label
- Sample Size
- 145
- Follow-up
- Up to 3 years; interim analysis data cutoff January 31, 2022; mean study duration 548 days
- Centers
- 51
- Countries
- Worldwide (Japan, Europe, North America)
Primary Outcome
Definition: Long-term safety and tolerability of efgartigimod, assessed by incidence and severity of TEAEs, SAEs, and abnormalities in vital signs, ECG, and laboratory assessments
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| N/A (single arm) | 84.8% had ≥1 TEAE; 23.4% had SAEs; 3.4% fatal TEAEs; safety profile maintained across up to 17 cycles | - |
Limitations & Criticisms
- Open-label, single-arm design without placebo control limits interpretation of long-term efficacy
- Interim analysis; final study data not yet available
- Limited assessment time points (weeks 0-3, then every 30 days year 1, every 90 days years 2-3) may not capture maximum improvements observed at week 4 in ADAPT
- Funded by argenx with employees as authors
- Selection bias: only patients who tolerated and wished to continue from ADAPT enrolled
- No formal statistical comparisons due to open-label design
- Small numbers in later cycles limit conclusions about long-term durability
- 56 participants rolled over to ADAPT-SC+ study, potentially introducing selection bias in remaining participants
- QMG only measured during first year (7 cycles), limiting long-term strength assessments
- 35 discontinuations (24.1%) over study period may affect generalizability
- COVID-19 pandemic occurred during study, potentially confounding safety data (15.2% had COVID-19)
Citation
Front Neurol. 2024;14:1284444