Changing treatment landscape in myasthenia gravis

Conventional immunosuppressants are widely used to treat patients with myasthenia gravis (MG) but come with many side effects and a delayed onset of action. Novel therapies have been arriving and may improve the situation for this patient population. Prof. Kristl Claeys (University Hospital Leuven, Belgium) discussed the current treatment landscape.

“Ineffectiveness, a delayed onset of action, and serious side effects are problems we encounter with conventional therapies for MG,” said Prof. Claeys. Fortunately, novel therapies are arriving, including complement C5 inhibitors, neonatal Fc receptor inhibitors, B-cell inhibitors, plasma cell inhibitors, and various cytokines and chemokines. Prof. Claeys mainly focussed on complement C5 inhibitors and neonatal Fc receptor inhibitors [1].

The neonatal Fc receptor inhibitor efgartigimod was tested among 167 patients with generalised MG in the phase 3 ADAPT trial [2]. The included participants were randomised 1:1 to receive efgartigimod as add-on therapy or to a placebo, for 26 weeks. A significantly larger proportion of participants on efgartigimod achieved an MG-ADL response (44/65 vs 19/64; P<0.0001). Efgartigimod had a favourable safety profile and displayed superior efficacy to placebo on other endpoints as well; results that led to the EMA approval of this agent for patients with generalised MG. “Next to efgartigimod, rozanolixizumab is an approved neonatal Fc receptor inhibitor for the MG population, and nipocalimab and batoclimab are still under investigation,” added Prof. Claeys.

Regarding complement C5 inhibitors, the phase 3 REGAIN trial compared eculizumab with a placebo in 125 patients with generalised MG [3]. The randomisation occurred in a 1:1 fashion and lasted for 26 weeks. “Although the primary endpoint of ‘MG-ADL change from baseline at week 26’ was not met, the results were good, and EMA approval was provided,” said Prof. Claeys. “Also, few adverse events were seen with this agent.” Ravulizumab and zilucoplan are other EMA-approved complement C5 inhibitors for the treatment of patients with generalised MG and pozelimab, cemdisiran, and gefurulimab are all being tested in phase 3 trials.

“The new biological therapies work faster, more selective, target-specific, and come with an acceptable safety profile,” summarised Prof. Claeys. “Nonetheless, there are many issues to be resolved, such as deciding which position these therapies take in the treatment cascade, collecting evidence on long-term efficacy and safety, and determining the value of these therapies during myasthenic crises.”

1. Claeys K, et al. Advances of treatments in myasthenia gravis. 10th EAN Congress, 29 June–2 July 2024, Helsinki, Finland.
2. Howard JF, et al. Lancet Neurol. 2021;20:526-536.
3. Howard JF, et al. Lancet Neurol. 2017;16(12):976-986.

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Posted on 25 July 202425 July 2024