Batoclimab Outperforms Placebo in Phase 3 Generalized MG Trial

New results from a phase 3 trial of batoclimab show the monoclonal antibody led to sustained improvement for patients with generalized myasthenia gravis (gMG), compared with placebo. The results, which were published in JAMA Neurology, raise hopes that a new treatment for MG could eventually gain regulatory approval.

MG is caused by autoantibody disruption of the neuromuscular junction, leading to chronic weakness of the skeletal muscles, explained the study authors. They said existing treatments include immunosuppressants, which are effective in some patients but lead to long-term adverse effects (AEs), and therapies that selectively reduce immunoglobulin G (IgG), which relieve symptoms but also have potential AEs.

The most recent additions to the MG armamentarium include efgartigimod (Vygart; Argenx) and rozanolixizumab (Rystiggo; UCB), which antagonize the neonatal fragment crystallizable receptor (FcRn), having the effect of reducing IgG concentration and improving MG symptoms.

In the new report, the investigators looked at another FcRn-focused therapy. Batoclimab is a fully humanized monoclonal IgG1 antibody that binds to FcRn and was found to be effective in a phase 2 trial of patients with gMG.

Investigators enrolled 132 patients in their phase 3 study, randomizing them 1:1 to receive batoclimab or placebo.

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This new phase 3 study enrolled 132 patients, only 1 of whom tested negative for both acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) antibodies. Two-thirds of the enrollees were women, and the mean age of the cohort was 43.8 years. Participants were randomized on a 1:1 basis to receive either batoclimab or placebo. Treatment consisted of 6 weekly subcutaneous 680-mg injections of batoclimab or placebo, followed by 4 weeks of observation. Patients requiring further treatment were given a second treatment cycle.

Using the MG Activities of Daily Living (MG-ADL) assessment, the investigators found patients taking batoclimab had significantly superior results starting at the second week of treatment compared with placebo.

“The rate of sustained MG-ADL improvement in the first cycle in antibody-positive patients was 31.3% (20 of 64) in the placebo group vs 58.2% (39 of 67) in the batoclimab group,” the authors found.

At day 43, patients in the placebo group had a mean (SE) improvement of 1.7 (0.3) points vs 3.6 points (0.3) in the batoclimab group.

“Batoclimab resulted in a rapid reduction in serum total IgG level, reaching the maximal mean reduction of 70.8% (1.2%) at week 6 in cycle 1 and returning to approximately 70% of baseline by week 9 (mean, –30.4% [1.6%]),” the authors said. “Batoclimab also led to a rapid and sustained reduction in AChR antibody, with a median (IQR) reduction of 81.1% (58.9%-86.3%) at week 6.”

In terms of AEs, 70.1% of participants in the batoclimab group had treatment-related AEs (TRAEs) compared with 36.9% of patients in the placebo group. Two participants in the batoclimab group had severe TRAEs compared with 5 in the placebo group.

The investigators noted that the 58% rate of sustained improvement in MG-ADL scores in this trial was lower than the 68% reported in a phase 3 trial of efgartigimod. However, they noted that the current trial used a more stringent definition of sustained improvement, requiring a 3-point reduction from baseline, vs a 2-point reduction in the efgartigimod trial.

“If a 2-point reduction in MG-ADL score was used as the threshold for sustained improvement, the rate of sustained improvement in this trial (65.7%) would have been similar to that reported for efgartigimod,” they added.

They said their study enrolled participants from 27 medical centers in China, representing a wide geographic swath of the country. However, they said the inclusion of just 1 patient who was AChR/MuSK negative represented a significant limitation. They also said their study was not long enough to assess the long-term safety and efficacy of the therapy, but they said an open-label extension trial is currently ongoing with that purpose.

Reference

Yan C, Yue Y, Guan Y, et al. Batoclimab vs placebo for generalized myasthenia gravis: a randomized clinical trial. J Neurol. Published online March 4, 2024. doi:10.1001/jamaneurol.2024.0044