Investigational Drug for Myasthenia Gravis Shows Promise in Improving Symptoms

Batoclimab, an investigational monoclonal antibody drug, significantly improved symptoms in adults with antibody-positive generalized myasthenia gravis (MG), according to the results of a multicenter phase 3 trial published in JAMA Neurology.

MG is a chronic condition characterized by muscle weakness, with a global prevalence of 15 to 25 per 100,000 individuals. Promising treatments that focus on immunoglobulin G (IgG) levels, such as efgartigimod and rozanolixizumab, have gained US Food and Drug Administration (FDA) approval for the treatment of acetylcholine receptor (AChR) antibody-positive generalized MG. Batoclimab, a monoclonal antibody targeting fragment crystallizable receptor (FcRn), is currently awaiting the results of its phase 3 trial for the treatment of MG.

Researchers conducted a multicenter randomized phase 3 clinical trial (ClinicalTrials.gov Identifier: NCT05039190), to assess the efficacy and safety of batoclimab in patients with generalized MG.

Eligible participants were of Chinese Han ethnicity, aged 18 and older with generalized MG, characterized by Myasthenia Gravis Foundation of America (MGFA) clinical classification IIa to IVa, MG-ADL score of 5 or greater with ocular score less than 50%, and a Quantitative Myasthenia Gravis (QMG) score of 11 or greater at screening.

The primary outcome was sustained improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) defined as a decrease of at least 3 points from baseline, sustained for a minimum of 4 consecutive weeks during the initial cycle. Secondary outcomes included sustained QMG improvement, total duration of MG-ADL improvement, minimal symptom expression, early MG-ADL improvement, and sustained MG-ADL improvement in cycle 2.

Initially, a total of 178 patients were screened of which 131 antibody positive patients were randomly assigned 1:1 to treatment groups (batoclimab group, n=67; vs placebo group, n=64). A single individual tested negative for both AChR and muscle-specific kinase (MuSK) antibodies and was assigned to the placebo group. Each treatment cycle involved administering 6 weekly subcutaneous injections of batoclimab at 68 0mg or placebo, followed by a 4-week period of observation without any treatment.

Among antibody-positive patients, the batoclimab group demonstrated a sustained MG-ADL improvement rate of 58.2% in the initial cycle, surpassing the placebo group’s rate of 31.3%. This yielded an odds ratio (OR) of 3.45 (95% CI, 1.62-7.35; P =.001).

By the second week, noticeable differences in MG-ADL scores emerged between the groups. By the time of the final dose, on day 43, compared to the placebo group, the batoclimab group demonstrated a significantly greater reduction in MG-ADL scores with a mean difference of -1.9 (95% CI, -2.8 to -1.0; nominal P <.001).

Both placebo and batoclimab groups had high rates of treatment-emergent adverse events (TEAEs) at 92.3% and 95.5% respectively. Severe TEAEs occurred in 7.7% of placebo patients and 3% of batoclimab patients.

Upper respiratory tract infection was the most common TEAE in the placebo group, affecting 21.5% of participants, followed by urinary tract infection (15.4%) and worsening of MG (12.3%). In contrast, peripheral edema was the most frequent TEAE in the batoclimab group, occurring in 38.8% of participants, followed by upper respiratory tract infection (35.8%) and urinary tract infection (19.4%).

Treatment interruptions due to TEAEs were slightly higher in the batoclimab group (4.5%) compared to placebo (3.1%). Batoclimab group had more treatment-related adverse events (TRAEs) at 70.1% vs 36.9% in the placebo group, with peripheral edema as the most reported TRAE in both groups.

Study limitations included its short duration with only 2 treatment cycles, inadequate investigation of long-term safety, especially regarding infections and cardiovascular events, and limited enrollment of only 1 patient with negative AChR/MuSK antibodies, constraining assessment of batoclimab efficacy in this subgroup.

“…[B]atoclimab is an important addition to the FcRn antagonist family from a global perspective, especially as a valuable alternative source of FcRn antagonist for China and the surrounding regions,” the researchers concluded. “This is particularly important considering the high mortality rate in hospitalized generalized MG patients in China.”

Disclosures: This study was supported by Nona Biosciences. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.