Impact of Batoclimab Treatment on LDL-C with and Without Coadministration of Atorvastatin: Results from a Phase I Randomized Study in Healthy Participants.

Introduction: Batoclimab is an anti-neonatal fragment crystallizable receptor monoclonal antibody in clinical development for the treatment of autoimmune diseases. In phase II trials, batoclimab resulted in dose-dependent reductions in pathogenic immunoglobulin G autoantibodies; however, dose-related increases in low-density lipoprotein cholesterol and other lipids were observed.

Objective: This study examined the relationship between batoclimab treatment and lipid levels, and whether increases in low-density lipoprotein cholesterol could be mitigated by coadministration with atorvastatin, a widely used cholesterol-lowering agent.

Methods: In this phase I, randomized, fixed-sequence, single-blind trial, 70 healthy participants received subcutaneous injections of batoclimab at various doses or placebo for 6 weeks. Open-label oral atorvastatin was coadministered in a subset of participants receiving batoclimab 340 mg or 680 mg weekly, starting 14 days before the first dose of the study drug, and continuing through the 6-week treatment period and 8-week safety follow-up. Key endpoints included changes in lipid parameters and atorvastatin pharmacokinetics.

Results: Dose-dependent increases in total cholesterol and low-density lipoprotein cholesterol were observed with batoclimab doses ≥ 255 mg weekly, comparable to previous observations, whereas coadministration of atorvastatin 10 mg or 40 mg daily mitigated these changes. Batoclimab had little effect on atorvastatin pharmacokinetics. Dose-dependent decreases in serum albumin up to 37% were observed with batoclimab doses ≥ 255 mg weekly, returning to near-baseline levels 4 weeks after stopping batoclimab. As expected, coadministration of atorvastatin did not meaningfully impact the albumin level. The majority of adverse events were mild in severity.

Conclusions: Atorvastatin can mitigate clinically significant increases in low-density lipoprotein cholesterol that may occur with batoclimab treatment.