Sustained gains with long-term Vyvgart use seen in ADAPT+ trial
Improvements seen in gMG patients regardless of antibody status
Repeat cycles of Vyvgart (efgartigimod alfa-fcab) led to consistent clinical improvements among generalized myasthenia gravis (gMG) patients, regardless of whether they were positive for antibodies against the acetylcholine receptor, according to interim findings from the ADAPT+ extension study.
Given the variability in how many treatment cycles each patient needed to see benefit, the researchers believe these data support the individualized dosing approach used with Vyvgart in clinical practice.
“This interim analysis … provides additional evidence that [Vyvgart] remained safe and well tolerated, with consistent and repeatable clinical improvements across multiple treatment cycles,” they wrote.
Findings were reported in the study, “Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis,” published in the journal Frontiers in Neurology. The work was funded by Argenx, Vyvgart’s developer.
Vyvgart treats myasthenia gravis by helping to clear self-reactive antibodies
Vyvgart works by blocking the activity of the neonatal Fc receptor (FcRn), a protein that normally stabilizes antibodies circulating in the bloodstream and prevents their degradation. As such, it promotes a faster clearance of the self-reactive antibodies that cause MG, lowering their levels in the blood to ease disease symptoms.
The medication is approved in the U.S. for adults with gMG who are positive for antibodies against the acetylcholine receptor (AChR), the most common type of MG-causing antibody.
Vyvgart is given in monthlong cycles, delivered by infusions (10 mg/kg) directly into the bloodstream once weekly for four weeks. After the first cycle, additional cycles can be initiated based on an individual’s clinical response.
Findings from the six-month Phase 3 ADAPT trial (NCT03669588), which enrolled 167 adults with gMG, demonstrated that Vyvgart effectively eased MG symptoms, relative to a placebo, as assessed by the MG Activities of Daily Living (MG-ADL) and the Quantitative MG (QMG) scales.
After the trial, 151 people opted to enroll in an open-label extension study called ADAPT+ (NCT03770403), where all received Vyvgart for up to three years.
This study, reporting final interim ADAPT+ trial data, cover findings in 145 patients given at least one dose of the therapy as of Jan. 31, 2022. Of them, 76.6% tested positive for anti-AChR antibodies.
ADAPT+ patients were followed for a mean of 548 days, or about 1.5 years, during which they received up to 17 treatment cycles.
Extension study supports treatment cycles based on patient response
Among the 95 anti-AChR antibody patients with at least one year of combined follow-up in ADAPT and ADAPT+, the mean number of yearly treatment cycles was 4.7. Many required fewer cycles: 24% received three or less, 18% were given two or less, and 6% needed one cycle.
This finding “supports an individualized treatment approach based on clinical evaluation,” the researchers noted.
As previously reported, clinically meaningful improvements in MG-ADL and QMG scores were observed during each Vyvgart treatment cycle for patients with anti-AChR antibodies. Such benefits occurred as soon as one week after the first infusion in the cycle, with the maximum improvements typically seen around the third week.
During the first cycle, mean MG-ADL scores improved by a maximum of five points, while QMG scores improved by 4.7 points. Similar gains were reported in subsequent cycles.
More than 90% of the AChR-positive patients achieved a clinically meaningful change (by at least two points) in MG-ADL scores during the first 10 treatment cycles, with around a quarter experiencing at least a nine-point change at week three of a cycle. Likewise, 69.4% to 91.3% achieved a clinically meaningful change (by at least three points) in QMG scores during the seven cycles where it was measured, with around a quarter seeing at least an eight-point change at week three.
Benefits noted in gMG patients who were negative for anti-AChR antibodies
Clinically meaningful improvements also were observed in patients without anti-AChR antibodies, with a maximum mean reduction of 5.3 points in MG-ADL scores and 5.2 points in QMG scores during the first cycle, and similar gains in subsequent cycles.
“These data are especially encouraging considering the significant disease burden and high unmet need experienced by [anti-AChR antibody-negative] patients,” the researchers wrote.
Maximum clinical improvements seen during each treatment cycle were associated with lower antibody levels in the bloodstream. Immunoglobulin G (IgG) are a family of antibodies circulating in the blood, including those against AChRs, that normally interact with FcRn.
Total IgG levels decreased during each treatment cycle, with a mean maximum reduction of 57% noted around week three of the first treatment cycle. Comparable reductions were seen in later cycles. Similar drops in anti-AChR antibodies were observed among patients positive for those antibodies at the study’s start.
Patients’ most frequent side effects were headache (24.8%) and cold-like symptoms (13.8%). COVID-19 infection also was noted in 15.2% of patients and was considered a treatment-emergent adverse event. Repeated treatment cycles did not cause an increase in side effects, including infections.
Antibodies against Vyvgart were found in 22 people, but in most cases, they had been present prior to treatment initiation. Such antibodies did not appear to affect the treatment’s safety nor efficacy, the researchers noted.
“Overall, these interim results of ADAPT+ support the long-term safety, tolerability, and efficacy of [Vyvgart] … for the treatment of patients with gMG,” the scientists concluded, noting that the findings also support “a long-term individualized treatment strategy for FcRn blockade in a broad population of patients with gMG.”