Discussion
PK/PD
SAID, THYROID EYE DISEASE, HERPES SIMPLEX INFECTION
This proof‐of‐concept study in patients with generalized MG demonstrated that a low‐volume SC injection of batoclimab was well tolerated and associated with significant reductions in both total IgG and anti‐AChR antibody concentrations. The safety profile of batoclimab was generally favorable and similar to the placebo arm throughout the study. There was one serious AE of herpes simplex infection, which led to hospitalization and discontinuation of study treatment and was considered by the investigator to be possibly related to treatment. Reductions in serum albumin were also observed, which is an expected effect based on the MOA of batoclimab, as FcRn recycles albumin using the same mechanism as for IgG. Low albumin concentrations were observed in 4 patients that received batoclimab 680 mg; however, albumin concentrations returned to baseline levels by end of the follow‐up period. No albumin‐related AEs were reported, and no low albumin concentrations were observed at the 340 mg batoclimab dose.Dose‐related elevations in serum lipids have been observed with batoclimab treatment, including in the Phase 2b trial in thyroid eye disease, which led to the early termination of that trial.Batoclimab treatment led to rapid declines in total IgG and anti‐AChR antibody concentrations, which were evident within 2 weeks after the first dose. These effects versus placebo were sustained throughout the double‐blind phase. Patients randomized to placebo received batoclimab during the OLE and also demonstrated antibody reductions when initiated on the lower dose of 340 mg every 2 weeks. The differential effects of batoclimab on individual subclasses of IgG were generally consistent with total IgG. As expected, batoclimab had no effect on IgA and IgM concentrations. The population that received batoclimab 680 mg was older and had a greater proportion of men compared with the batoclimab 340 mg and placebo groups; this is likely a product of randomization in a small study and does not affect safety and efficacy endpoints given that similar trends were observed in the batoclimab 340 mg group.FcRn inhibition has been shown to be an effective mechanism by which to treat MG.The study has several limitations. The sample size was small and there were some imbalances across groups with respect to baseline characteristics. In particular, patients who received placebo during the double‐blind period were younger than those who received batoclimab. In addition, the mean (SD) time since MG onset was approximately 5 years in batoclimab patients and approximately 7 years in placebo patients. The heterogeneity of the patient population and short duration of the treatment period may also help to explain the smaller effect on clinical measures that were observed with the 680‐mg versus the 340‐mg dose of batoclimab, despite greater reductions in IgG and anti‐AChR antibodies with the 680‐mg dose. As this Phase 2a proof‐of‐concept study was designed primarily as a PK/PD and safety trial, it was not powered to evaluate clinical efficacy. Additionally, there was a lack of racial and ethnic diversity that limits the generalizability of the results. That said, based on the findings of this study, further evaluation of batoclimab as a possible future treatment option for patients with gMG is being explored in a registrational Phase 3 trial (In conclusion, the results of this Phase 2a trial demonstrated that SC batoclimab is well tolerated and significantly reduced IgG and anti‐AChR antibody levels in patients with gMG, supporting its further investigation as a potential patient‐administered therapeutic agent for MG.