MDA 2023: Vyvgart of benefit across gMG duration, antibody status
ADAPT, ADAPT+ findings detailed in AChR-positive and -negative groups
Vyvgart (efgartigimod) eased symptoms of generalized myasthenia gravis (gMG) in patients regardless of their disease length, treatment history, or acetylcholine receptor (AChR) antibody status, according to two new analyses from the ADAPT clinical trial and its open-label extension, ADAPT+.
These findings serve to reinforce “the efficacy of efgartigimod across a broad gMG population,” according to the researchers.
Data were presented by scientists from Argenx, Vyvgart’s developer, across two poster presentations at the MDA Clinical & Scientific Conference, being held March 19-22 in Dallas and virtually.
Good responses seen with Vyvgart across disease lengths, current treatments
The Argenx-sponsored Phase 3 ADAPT trial (NCT03669588) enrolled 167 adults with gMG, including 129 people with anti-AChR antibodies. All were randomly assigned to receive Vyvgart at 10 mg/kg or a placebo, infused directly into the bloodstream, for about six months in addition to current therapies. Of note, AChR antibodies are the most common type of self-reactive antibodies found in MG patients.
After an initial treatment cycle consisting of a single weekly infusion for four weeks, the trial used an individualized treatment approach with subsequent dosing cycles based on clinical response.
Vyvgart’s efficacy was evaluated with two standard questionnaires of disease severity: the MG Activities of Daily Living (MG-ADL) and the Quantitative MG (QMG). Treatment responders were defined as those experiencing at least a two-point improvement (reduction) for at least four consecutive weeks on the MG-ADL, or a three-point improvement on the QMG over the same time frame.
Top-line trial data indicated that ADAPT met its main goal and key secondary goals, with a higher proportion of AChR-positive patients treated with Vyvgart achieving a response on the MG-ADL and QMG after the first treatment cycle. Additional analyses indicated similar benefits in the smaller group of patients who lacked anti-AChR antibodies.
In the poster “Efgartigimod Demonstrates Consistent Improvements in Generalized Myasthenia Gravis Across Patient Subgroups, Including Early in Diagnosis,” researchers explored whether treatment responses differed among subgroups of AChR-positive patients. Specifically, scientists wanted to know whether disease length or treatment history influenced MG-ADL and QMG responses.
Patients here were split in three groups, depending on how long they had been living with gMG: less than three years, between three and up to six years, or for six years or longer. Across these groups, the proportion of treatment responders based on MG-ADL or QMG always was higher in Vyvgart-treated patients than in those given a placebo.
Similarly, more Vyvgart-treated patients experienced a meaningful response to treatment regardless of other current therapies, including acetylcholinesterase inhibitors (e.g., Mestinon), steroids, or non-steroidal immunosuppressants. Likewise, previous use of non-steroidal immunosuppressants or a thymectomy — surgery to remove the thymus gland — didn’t influence treatment response to Vyvgart.
Overall, Vyvgart “demonstrates consistent improvements compared to placebo,” the researchers wrote, noting the findings support its use for “a broad patient population, including early in disease, and early in the treatment journey of patients with gMG.”
After ADAPT concluded, 151 patients opted to continue or start using Vyvgart for up to three years in ADAPT+ (NCT03770403), its open-label extension study. Long-term Vyvgart use, up to 10 treatment cycles in ADAPT+, was associated with consistent and clinically meaningful improvements in MG-ADL and QMG scores among 106 people with anti-AChR antibodies and 33 without them, a previous analysis reported.
Responses also seen among most of 37 AChR-negative patients in trials
In the poster, “Efficacy, Safety, and Tolerability of Efgartigimod in AChR-Ab– Patients With Generalized Myasthenia Gravis: Interim Analysis of ADAPT/ADAPT+ Studies,” researchers discussed long-term findings from 37 AChR-negative patients given at least one dose of Vyvgart in ADAPT or ADAPT+ as of October 2020.
Patients without anti-AChR antibodies are historically underrepresented in clinical trials, and Argenx reports that ADAPT and ADAPT+ are the first clinical studies to include them. Such patients, 19 of whom started receiving Vyvgart in the main trial and 18 who began treatment in ADAPT+, had been followed for a median of 453 days, or about 1.2 years.
MG-ADL response rates were 61.1% in the main trial and 79.4% in ADAPT+. QMG response rates were 66.7% in ADAPT and 63.3% in ADAPT+. These response rates were similar overall to those observed among antibody-positive patients, but there were higher placebo response rates among the antibody-negative group, the researchers noted.
Clinically meaningful improvements in MG-ADL and QMG scores were observed after the first treatment cycle and sustained through at least 10 cycles.
Safety findings also were similar to those previously observed in AChR-positive patients, with no new safety signals identified.
“Additional studies assessing the efficacy of efgartigimod in [AChR-negative] patients are warranted,” the researchers wrote.