AAN 2023: Longer-term benefits seen with under-skin efgartigimod
Therapy for gMG shows efficacy, no new safety issues in study data
Repeated treatment with under-the-skin efgartigimod had a consistent effect in easing symptoms of generalized myasthenia gravis (gMG), with no new safety issues identified.
That’s according to interim data from the Phase 3 extension study ADAPT-SC+ (NCT04818671), which is continuing treatment with the experimental formulation in people with gMG.
The data was presented in a poster, titled “Long-Term Safety, Tolerability, and Efficacy of Subcutaneous Efgartigimod PH20 in Patients with Generalized Myasthenia Gravis: Interim Results of the ADAPT-SC+ Study,” at the recent American Academy of Neurology (AAN) 2023 Annual Meeting, held in Boston and virtually. The work was funded by Argenx.
Efgartigimod is the active ingredient in Argenx’s Vyvgart, an intravenous (into-the-vein) therapy approved in the U.S. for gMG since 2021. It works by lowering the levels of the self-reactive antibodies that drive MG.
Aiming to improve treatment convenience, Argenx developed a subcutaneous version of efgartigimod, which can be given by an under-the-skin injection that’s easier to administer. This subcutaneous version is now up for approval by the U.S. Food and Drug Administration (FDA). A decision from the FDA originally was expected in March, but Argenx announced in January that the regulatory agency was extending its review. A decision now is expected to be announced in June.
New data presented at AAN annual meeting
Vyvgart is administered via hour-long infusions into the bloodstream. It’s given in cycles of four weekly infusions, with additional treatment cycles given as needed to control symptoms.
The subcutaneous formulation of efgartigimod has been tested in clinical trials using a similar schedule.
Argenx’s application requesting its approval was supported by data from the ADAPT-SC trial (NCT04735432), which compared the investigational formulation against Vyvgart in 110 people with gMG. Results from the Phase 3 trial showed both formulations were similarly effective at reducing antibody levels.
Most patients who completed ADAPT-SC opted to enter into an open-label extension study, called ADAPT-SC+, to continue treatment with subcutaneous efgartigimod. This study, which is still ongoing, also included patients who had participated in prior trials of Vyvgart. Most patients were positive for antibodies against the acetylcholine receptor (AChR), the most common type of MG-causing antibodies.
In ADAPT-SC+, participants are being treated with subcutaneous efgartigimod given in cycles of four weekly injections as needed, with at least a month of interval between each cycle — mirroring the schedule used for Vyvgart infusions.
The poster presented at AAN covered interim data from 164 gMG patients who received at least one dose of subcutaneous efgartigimod during ADAPT-SC+. Over a median follow-up time of about six months, most of these patients received three cycles of treatment.
The results suggested that each cycle of treatment led to a consistent effect on disease symptoms. Specifically, by the end of each cycle, scores on the MG Activities of Daily Living (MG-ADL), a patient-reported measure of symptom severity, had improved by about four points on average. About one-third of patients had an MG-ADL score of 0 or 1, suggesting minimal symptoms, at the end of each cycle.
Quality of life scores also showed a consistent effect across each of the three treatment cycles, and antibody levels consistently dropped by about 60% after each cycle. Analyses conducted only in anti-AChR-positive patients showed similar results to that of the overall patient population.
Results suggest that treatment with multiple cycles of [subcutaneous efgartigimod] was well tolerated, with no new safety signals identified.
Safety data from the trial have been consistent with previous studies of efgartigimod. Commonly reported side effects included injection site reactions like redness, itching, or pain, as well as infections such as COVID-19 and the common cold. Injection site reactions, which were mild to moderate and did not lead to treatment discontinuation, were more likely to occur in the first cycle of treatment, becoming less common with subsequent cycles.
“Results suggest that treatment with multiple cycles of [subcutaneous efgartigimod] was well tolerated, with no new safety signals identified,” the researchers wrote.
Overall, the safety and efficacy findings from the subcutaneous efgartigimod formulation have been consistent with prior studies of the approved version of Vyvgart, the researchers noted.
Note: The Myasthenia Gravis News team is providing coverage of the American Academy of Neurology (AAN) 2023 Annual Meeting April 22-27. Go here to see the latest stories from the conference.