Efgartigimod shows promise in treatment-resistant myasthenia gravis

Use of efgartigimod, a first-in-class investigational antibody fragment targeting the neonatal Fc receptor (FCRN), demonstrates both efficacy and safety in patients with refractory, treatment-resistant generalized myasthenia gravis (MG), as shown in a study presented at EAN 2024.

“No rescue treatment was required,” said lead study author Dr Joana Dionisio from the Department of Neurology, Kings College Hospital London, UK. “At the end of the study, 96 percent of patients remained on efgartigimod.” [EAN 2024, abstract EPO-200]

Dionisio and her team retrospectively obtained data from all UK patients treated with efgartigimod under the early access to medicine scheme (EAMS) from June 2022 to July 2023. The study drug was administered according to the ADAPT protocol (treatment cycle of four infusions at weekly intervals with further cycles given as per clinical need).

“We report our experience of patients with generalized MG treated with efgartigimod, an FCRN antagonist, under the EAMS in the UK,” Dionisio said.

The study included 48 patients with AchR antibody positive generalized MG who received treatment in 13 centres in the UK. Of the participants, 76 percent were female. Most of them had a disease duration of more than 10 years. Their average MG Activities of Daily Living (ADL) score at baseline was 11.2.

Majority of the patients with generalized MG (73 percent) underwent thymectomy, and most (71.4 percent) had been taking prednisolone at baseline. Nonsteroidal immunosuppressant treatments had also been used by all patients, with an average number tried of 2.4. Additionally, more than half of these individuals (52.1 percent) were treated with rituximab.

Fifty-seven percent of patients required regular intravenous immunoglobulin (IVIg) and plasma exchange (PLEX), while 38 percent had a need for rescue IVIg/PLEX in the year before initiating efgartigimod, according to Dionisio.

Efficacy and safety

In the first cycle of treatment, 77 percent of patients with generalized MG showed a mean decrease of ≥2 points in the MG-ADL scale, “and this remained stable throughout the study.” The mean reduction in the MG-ADL score was ‒4.5 in the first cycle, ‒6.3 in the second cycle, ‒6.9 in the third cycle, and ‒7.8 in the fourth cycle.

In terms of safety, one side effect each occurred during cycles 1, 2, and 3. Most of these were mild in severity, although one patient discontinued treatment due to severe hypokalaemia. In addition, three patients had infections (ie, SARS-CoV-2, UTI, and severe peg site infection), seven had headaches or flu-like symptoms, and one experienced bruising.

“Despite providing important details regarding [the efficacy of efgartigimod] in generalized MG, its positioning and timing in the treatment algorithm remains elusive,” Dionisio said. “It is also important to identify important side effects with long-term use and its potential in pregnancy and breastfeeding.”

The study was limited by its small sample size, the heterogeneous group of patients, and the variability of the timing of efgartigimod treatment, “which were also dependent on the clinicians’ and patients’ assessment of their disease severity.” Moreover, data on prednisolone dose reduction to assess the steroid-sparing effect was not available.