Immunovant announced a voluntary pause of dosing in its ongoing clinical trials of its investigational drug IMVT-1401 for the treatment of Thyroid Eye Disease (TED).
The company has become aware of a physiological signal consisting of elevated total cholesterol and LDL levels in IMVT-1401-treated patients in ASCEND GO-2, a phase 2b trial in TED. Cholesterol levels were not measured in prior clinical trials of IMVT-1401 in Myasthenia Gravis (MG) and in healthy subjects.
“Out of an abundance of caution, the company has decided to voluntarily pause dosing in ongoing clinical studies in both TED and in Warm Autoimmune Hemolytic Anemia, in order to inform patients, investigators, and regulators as well as to modify the monitoring program,” according to a company news release.
ASCEND GO-2 is a randomized, placebo-controlled trial in TED evaluating different doses, each given weekly for 12 weeks. In this study, cholesterol parameters are assessed at baseline, at 12 weeks, and at week 20 following 8 weeks off drug. Based on preliminary, unblinded data from about 40 patients through week 12, mean LDL cholesterol at week 12 was increased by approximately 65% in the 680mg dose group, by approximately 40% in the 340mg dose group, and did not increase in the control group. Average HDL and triglyceride levels increased to a much lesser degree. For context, commercially available statins report a reduction in LDL cholesterol between 27-60%. At the 20-week timepoint, average LDL levels had declined to baseline or lower in the 680mg dose group, in the 340mg dose group, and in the control group. No serious cardiovascular events have been reported to date in IMVT-1401 clinical trials.
Harbour BioMed, the license holder for 1401 in Greater China, has informed Immunovant that based on their preliminary review of blinded data in their ongoing clinical studies in Chinese patients with MG and Idiopathic Thrombocytopenic Purpura, similar increases in cholesterol have not been observed. The company is not aware whether trials involving other anti-FcRn agents in development have performed detailed assessments of lipid parameters.
The company will work closely with regulators and scientific experts to characterize the detailed profile of these lipid changes and to understand the mechanism of these changes across indications. After discussion and agreement with regulators regarding protocol modifications, the company intends to continue to pursue development of IMVT-1401.