Data showed that efgartigimod led to greater improvements in disease activity compared with placebo in idiopathic inflammatory myopathy, and improvements in seronegative myasthenia gravis.
New data from the 24-week phase 2 ALKIVIA study (NCT05523167) showed that treatment with of subcutaneous (SC) efgartigimod (Vyvgart Hytrulo; argenx), a neonatal Fc receptor (FcRn) blocker, significantly reduced disease activity compared with placebo in patients with Idiopathic inflammatory myopathy (IIM), a rare autoimmune disorder with different subtypes. The results highlight the therapeutic potential of FcRn inhibition in IIM and further support continued evaluation of efgartigimod in the ongoing phase 3 ALKIVIA+ study (NCT05979441).1,2
Presented at the
“We’re proud to have a robust presence at this year’s AANEM Annual Meeting and MGFA Scientific Session, where we are sharing pivotal data and meaningful evidence across a broad spectrum of serious neuromuscular diseases, including MG, CIDP, MMN, and IIM,” Luc Truyen, MD, PhD, chief medical officer at argenx, said in a statement.2 “The breadth of studies reflect[s] the strength and momentum of our clinical development programs, from the continued expansion of VYVGART into new patient populations, to our fast-approaching growth opportunity with empasiprubart. These presentations also underscore our commitment to generating evidence that propels innovation and positively impacts people living with these debilitating diseases.”
Led by Rohit Aggarwal, MD, MS, medical director of Rheumatology at the University of Pittsburgh, ALKIVIA is a phase 2/3, randomized, double-blinded, placebo-controlled, parallel-group, multicenter study assessing the efficacy and safety of SC efgartigimod PH20 compared with placebo in adults with IIM receiving standard of care medications. Participants who were included had subtypes of dermatomyositis, immune-mediated necrotizing myositis, polymyositis, or antisynthetase syndrome. Researchers randomized participants 1:1, stratified by IIM subtype and disease severity, to receive weekly treatment of efgartigimod PH20 SC or placebo plus standard of care.
In a recent NeurologyLive Peer Exchange, an expert panel of James F. Howard Jr, MD, FAAN; Beth Stein, MD; Andrew Gordon, MD; and Ratna Kiran Bhavaraju-Sanka, MD, discussed how different FcRn inhibitors vary in administration routes, dosing schedules, and adverse event profiles. Additionally, they highlighted that patients may respond differently to various agents, requiring individualized treatment approaches.
WATCH THE DISCUSSION HERE: FcRn Inhibitors for Treatment of Myasthenia Gravis
The primary end point of the trial was the 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology TIS at 24 weeks. This composite end point includes of Physician's Global Disease Activity (MDGA), Patient Global Disease Activity (PGA), manual muscle testing-8 (MMT8), Health Assessment Questionnaire Disability Index, muscle enzymes, and Extramuscular Global Disease Activity. Key secondary end points of the study were time to reach a TIS of at least 20 and at least 40, and proportion of patients achieving a TIS of at least 20 and at least 40 and the changes in MMT8, PGA, and MDGA at 24 weeks.
Researchers reported that the key secondary end points of the trial were met, except for minimal clinical improvement, TIS of at least 20, at week 24 (91.5% vs 73.8%). Findings revealed that median times to a TIS of at least 20 and of at least 40 were significantly shorter with efgartigimod than with placebo (30 days vs 71.5 days, P = .0020; and 113 days vs not estimable, P = .0293, respectively). Moreover, a higher proportion of participants in the efgartigimod group had a moderate TIS of at least 40, and major TIS of more than 60, clinical improvement at 24 weeks compared with the placebo group (78.7% vs 47.6% and 34.0% vs 9.5%, respectively).
Authors noted that the proportion of patients who experienced at least 1 adverse event (AE) was similar in the 2 treatment groups (efgartigimod, 87.2%; placebo, 88.1%). Notably, a grade of at least 3 AEs occurred in 14.9% of participants in the efgartigimod treatment group and 28.6% of patients in the placebo group. Serious AEs occurred in 17% of patients in the efgartigimod arm and 21.4% in the placebo arm. The most common AEs in the efgartigimod arm included injection site erythema (23.4%), rash (17.0%), bruising (10.6%) or reaction (10.6%), and diarrhea (12.8%). Researchers reported that there were 2 deaths in the efgartigimod PH20 SC arm, both unrelated to the study drug, and none in the placebo arm.
In addition to ALKIVA, argenx presented new, promising data from the phase 3 ADAPT SERON trial (NCT06298552) testing efgartigimod in patients with seronegative generalized myasthenia gravis (gMG). In August,
Overall, the trial met its primary end point, with patients achieving statistically significant improvements in the primary end point of MG-ADL (P = .0068) total score over a 4-week stretch. Patients on the approved medication demonstrated a clinically meaningful 3.35-point improvement during that time, coupled with improvements in breathing, eating, eyesight, and motor functions.
The company noted in a release that it intends to share the results of the trial with the FDA to seek an expansion of the therapy's label to include adult AChR-Ab seronegative gMG patients across all 3 disease subtypes.
In ADAPT-SERON, improvements in MG-ADL and Quantitative Myasthenia Gravis score, a secondary end point, were increasingly pronounced across subsequent treatment cycles in the overall population. Notably, these improvements were found in multiple different subgroups, including those with MuSK gMG, LRP4+, and triple seronegative. Encouragingly, the drug was considered well-tolerated across AChR-antibody seronegative subtypes and consistent with the established safety profile.
"The ADAPT SERON trial showed that efgartigimod generated tangible improvements in daily functioning, marking an important advancement for the field and for seronegative patients seeking better disease control. Patients with seronegative gMG, in particular, have historically lacked effective treatment options. Collectively, these findings highlight that efgartigimod has the potential to deliver meaningful and progressive benefits for patients regardless of antibody status, with its therapeutic impact strengthening through continued treatment," Principal Investigator James F. Howard Jr., MD, a professor of neurology, medicine, and allied health in the Department of Neurology at the University of North Carolina at Chapel Hill School of Medicine, said in a statement.2
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