Impact of Batoclimab Treatment on LDL-C with and Without Coadministration of Atorvastatin: Results from a Phase I Randomized Study in Healthy Participants
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: 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. 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. 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. 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. Atorvastatin can mitigate clinically significant increases in low-density lipoprotein cholesterol that may occur with batoclimab treatment. Batoclimab is a monoclonal antibody in clinical development to treat autoimmune diseases. Previous clinical studies of batoclimab reported reductions in autoimmune disease-causing immunoglobulin G antibodies as the batoclimab dosage increased. However, dose-related increases in cholesterol and other lipids were also observed. This phase I, randomized clinical study sought to examine the relationship between batoclimab treatment and lipid levels. It also investigated whether coadministration of batoclimab with atorvastatin, a common cholesterol-lowering medication, could mitigate the cholesterol increases. Seventy healthy participants received regular injections of batoclimab (various doses) or placebo for 6 weeks. A subset of participants receiving batoclimab (340 mg or 680 mg) were coadministered oral atorvastatin starting 14 days before batoclimab or placebo treatment and continuing through the 6-week treatment and 8-week safety follow-up periods. Key outcomes of the study included changes in lipid levels and the metabolism of atorvastatin. As observed in previous studies, participants treated with batoclimab doses ≥ 255 mg weekly had dose-dependent increases in cholesterol. Coadministration of atorvastatin (10 or 40 mg daily) mitigated these cholesterol increases. Batoclimab had little effect on the metabolism of atorvastatin. Participants treated with batoclimab doses ≥ 255 mg weekly had dose-dependent decreases in serum albumin of up to 37%, which returned to near-baseline levels 4 weeks after stopping batoclimab treatment and were not meaningfully impacted by atorvastatin coadministration. The majority of adverse health events were mild in severity. This study suggests that atorvastatin coadministration may mitigate increases in cholesterol that may occur with batoclimab treatment for autoimmune diseases.
Source: Drug Safety
Authors: Thomas Hardy, Su Liang, Philip Tedeschi, E Lin, Eliot A. Brinton, Michael H. Davidson
Institution: University of Chicago
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
OpenAlex ID: W4409843678