AAN 2024: Many Vyvgart-treated patients have few, if any, symptoms
Quality of life improved for participants in ADAPT trial and its extension study
Many of the adults with generalized myasthenia gravis (gMG) who took part in ADAPT, a Phase 3 clinical study of Vyvgart (efgartigimod), and its open-label extension, ADAPT+, experienced minimal or no symptoms and a quality of life closer to that of healthy adults.
While Vyvgart is approved to be given once weekly over cycles of four weeks, every-other-week continuous dosing appears to work just as well, broadening options for more personalized treatment, according to data from an ongoing Phase 3 clinical trial called ADAPT NXT.
These findings were presented in two separate posters at the recent American Academy of Neurology (AAN) 2024 Annual Meeting, in Denver, Colorado, and online. Both studies were supported by Argenx, the company that developed and now markets Vyvgart.
Vyvgart works by blocking the action of neonatal Fc receptor (FcRn), a protein that helps antibodies stay longer in the circulation by preventing their degradation. By blocking FcRn, Vyvgart increases the rate at which antibodies circulating in the blood are broken down, including the harmful ones that cause gMG. Through this mechanism, Vyvgart is expected to lower the levels of MG-causing antibodies and ultimately ease disease symptoms.
Vyvgart approved for adults with gMG with antibodies against AChR
Infused once weekly over four-week cycles, Vyvgart is approved for adults with gMG who have antibodies against the acetylcholine receptor (AChR), which is the most common type of self-reactive antibodies that disrupt nerve-muscle communication in people with MG.
In the pivotal study, ADAPT (NCT03669588), and its open-label extension, ADAPT+ (NCT03770403), treatment with Vyvgart led to clinically meaningful improvements in daily function that were sustained over multiple cycles of treatment. This was evaluated by assessing changes in the scores on the MG Activities of Daily Living (MG-ADL) scale.
In a new analysis, researchers looked at changes in an exploratory measure called minimal symptom expression (MSE), wherein achieving minimal or no symptoms is defined as having an MG-ADL score of zero or 1 out of a maximum of 24. On the MG-ADL scale, a lower score indicates less impact of the disease on daily function.
Significantly more Vyvgart-treated patients achieved MSE during the ADAPT study than those on a placebo (44.6% vs. 10.9%), according to a poster presented by Srikanth Muppidi, MD, a clinical professor at Stanford University School of Medicine in California.
The poster was titled “Achievement of Minimal Symptom Expression and Effect on Disease-specific Measures in Acetylcholine Receptor Antibody-positive Participants with Generalized Myasthenia Gravis Treated with Efgartigimod in ADAPT/ADAPT+.”
Benefits evident as early as first treatment cycle
The difference was evident as early as the first cycle of treatment, and was sustained throughout the ADAPT+ study, where patients received up to 19 treatment cycles. As many as 81% of Vyvgart-treated patients who had achieved MSE in ADAPT — and 23% of those who hadn’t — achieved MSE during the ADAPT+ study.
Achieving MSE wasn’t linked to a difference in patient characteristics at baseline, or at the study’s start.
“In ADAPT, participants who achieved MSE had similar baseline disease severity and symptom burden to those who did not achieve MSE,” the researchers wrote in the poster.
Of the 29 patients who achieved MSE during ADAPT, many also had “sustained improvements” in other measures of disease severity and health-related quality of life, suggesting MSE could be a way to measure response to treatment.
For example, patients who achieved MSE had a mean reduction of 11.4 points on the Quantitative MG questionnaire, where a higher score indicates more severe symptoms, and a reduction of three points or more is considered clinically meaningful.
Improvements seen in quality-of-life scores
In the EQ-5D-5L, which measures quality of life on a scale from 0 to 100, with a higher score indicating better health status, there was an increase from a score of 57.8 at baseline to a best (maximal) score of 85.8. In more than one-third (39.5%) of visits, the score reached 78 points or greater, which is the norm for the healthy population.
Consistent with earlier reports, side effects “were predominantly mild to moderate and did not increase in frequency during long-term treatment in ADAPT+,” the researchers wrote.
In another poster, “Fixed Cycle and Every-Other-Week Dosing of Intravenous Efgartigimod for Generalized Myasthenia Gravis: Part A of ADAPT NXT,” Vera Bril, MD, of the Toronto General Hospital in Canada presented data from the two-part ADAPT NXT trial (NCT04980495).
In part A, 69 adults with gMG who tested positive for anti-AChR antibodies were randomly assigned to receive three cycles of four once-weekly infusions of Vyvgart, or every-other-week infusions following an initial four-week cycle, for 21 weeks (about five months). In part B, they continue treatment for up to 105 weeks, or two years.
Both schemes “resulted in clinically meaningful improvements in MG-ADL scores,” the researchers wrote, noting improvements were evident as early as the first week. After 21 weeks, the adjusted average reduction in MG-ADL scores was 5.13 for the cyclic scheme and 4.61 for the continuous scheme.
The proportion of patients who achieved MSE after 21 weeks of treatment was also similar (47.1% vs. 44.2%). However, the proportion of patients who experienced a reduction of eight points or more in the MG-ADL scale appeared to be greater among those treated with the continuous scheme.
Vyvgart was well tolerated regardless of the scheme used, suggesting additional data coming from the ADAPT NXT study may offer “further options to individualize” treatment for gMG patients, the researchers concluded.
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