Abstract
Efgartigimod (Vyvgart®; Vyvgart® Hytrulo) is a neonatal fragment crystallizable receptor (FcRn) antagonist indicated for the treatment of generalised myasthenia gravis (gMG) in adults who are acetylcholine receptor (AChR) antibody positive (Ab+). Efgartigimod is approved for both intravenous (IV) and subcutaneous (SC) use. In a pivotal phase III trial, IV efgartigimod was associated with significant and clinically meaningful improvements in myasthenia gravis symptoms and reductions in disease burden. The beneficial effects of IV efgartigimod were reproducible, durable and maintained over the long term. IV efgartigimod also improved health-related quality of life (HRQOL). In another phase III trial, SC efgartigimod PH20 was noninferior to IV efgartigimod in reducing total immunoglobulin G levels. Clinical improvement with SC efgartigimod PH20 was consistent with that of IV efgartigimod and was reproducible over the long term. Efgartigimod was generally well tolerated; the most common adverse events were headache and infections (with IV efgartigimod) and injection-site reactions (with SC efgartigimod PH20). Although further long-term data are required, IV and SC formulations of efgartigimod provide effective, generally well-tolerated and flexible treatment options for adults with AChR Ab+ gMG.
Smith AG, Wolfe GI, Habib AA, Qi CZ, Yang H, Du M, Chen X, Gelinas D, Brauer E, Phillips G, Saccà F. Risk-Benefit Analysis of Novel Treatments for Patients with Generalized Myasthenia Gravis. Adv Ther. 2024 Dec;41(12):4628-4647. doi: 10.1007/s12325-024-03014-5. Epub 2024 Oct 29. PMID: 39470879; PMCID: PMC11550228.
Abstract
Introduction: This study used network meta-analysis (NMA) to inform and compare the number needed to treat (NNT), number needed to harm (NNH), and cost per improved outcome (CPIO) associated with more recently approved treatments for anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) generalized myasthenia gravis (gMG).
Methods: Clinical trials of neonatal Fc receptor (FcRn) inhibitors, efgartigimod intravenous (IV) and rozanolixizumab, and complement inhibitors, ravulizumab and zilucoplan, versus placebo (with background conventional treatment) were included in the primary NMA to compare efficacy and safety outcomes. The outputs from the NMAs were used to estimate NNT and NNH of each treatment versus placebo. CPIO (2024 USD) was estimated for a ≥ 3- or ≥ 5-point reduction from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores. Sensitivity analyses were performed adding efgartigimod PH20 subcutaneous (SC) and eculizumab to the NMA.
Results: Efgartigimod IV had the lowest NNT versus placebo for achieving a ≥ 3- and ≥ 5-point reduction in QMG, as well as a ≥ 5-point reduction in MG-ADL, whereas rozanolixizumab had the lowest NNT for a ≥ 3-point reduction in MG-ADL. The NNH versus placebo was similar across comparator treatments. Efgartigimod IV had the lowest CPIO among all treatments for all assessed efficacy outcomes. Sensitivity analyses yielded results consistent with primary analysis and indicated that efgartigimod PH20 SC had comparable NNT and CPIO values to efgartigimod IV, whereas eculizumab had comparable NNT and higher CPIO values compared to other complement inhibitors.
Conclusions: FcRn inhibitors and complement inhibitors assessed in this study all demonstrated clinical benefit in terms of NNT as well as an acceptable safety profile in terms of NNH. Within the limitations of this meta-analysis, efgartigimod was associated with a favorable benefit-risk profile as well as a better economic value compared to ravulizumab, rozanolixizumab, and zilucoplan as treatments for anti-AChR Ab+ gMG.
Dewilde S, Griffiths A, Qi CZ, Phillips G, Gelinas D, Brauer E, Mantegazza R, Howard JF Jr. Post-hoc analyses from the ADAPT clinical study demonstrate aggregate sustained benefit of Efgartigimod in generalized myasthenia gravis. J Neurol Sci. 2024 Nov 15;466:123264. doi: 10.1016/j.jns.2024.123264. Epub 2024 Oct 4. PMID: 39426360.
Abstract
Objectives: This post-hoc analysis evaluates the long-term efficacy of efgartigimod versus placebo in adult patients with generalized myasthenia gravis (gMG) with acetylcholine-receptor autoantibodies (AChR-Ab+), based on data from the ADAPT RCT and its open-label extension ADAPT+.
Methods: Changes from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores were assessed by treatment group over the ADAPT (up to 20 weeks) and ADAPT+ time horizon (extended to 64 weeks for efgartigimod group patients). Response to treatment was defined as 5-point reduction in QMG or 3-point reduction in MG-ADL vs. baseline values.
Results: AChR-Ab+ patients treated with efgartigimod spent a substantially greater percentage of time in response in ADAPT based on at least a 5-point change in QMG compared to the placebo group (44 % versus 13 % respectively, p = 0.0034). Analyses based on a 3-point change in MG-ADL in ADAPT showed the percentage of time in response was nearly double for efgartigimod versus placebo (59 % versus 30 % respectively, p = 0.010). These trends were also maintained using different response definitions, as well as in patients with and without prior immune therapy exposure and by time from diagnosis (<7 years versus ≥7 years).
Conclusions: The clinical benefit of efgartigimod was sustained over repeat treatment cycles and maintained over the long term. Response to treatment was consistent regardless of response definition and was repeated in different patient subgroups. Overall, the results of this analysis indicate that efgartigimod is an effective therapeutic option, demonstrating a robust benefit among AChR-Ab+ patients with gMG.
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