Immunovant Planning Pivotal Trial of IMVT-1401

Following a review of available clinical data, Immunovant has announced plans to resume clinical testing of the investigational medication IMVT-1401 in myasthenia gravis (MG) and other autoimmune conditions.

Following discussions with regulatory agencies, the company is planning to launch a potentially pivotal trial of IMVT-1401 in MG, and to resume a Phase 2a study (NCT04253236) of the investigational medication in warm autoimmune hemolytic anemia, an autoimmune disease in which the body’s immune system wrongly attacks red blood cells.

These trials are expected to start later this year or early next year. Additional trials of IMVT-1401 in other autoimmune diseases also are expected to be launched in the coming year.

“Following a program-wide data review, we remain confident in our plan to develop IMVT-1401 across a broad range of autoimmune indications,” Pete Salzmann, MD, Immunovant’s CEO, said in a press release.

Earlier this year, Immunovant paused all ongoing clinical trials of IMVT-1401, after data from a Phase 2b trial (NCT03938545) in people with thyroid eye disease (TED) — a condition characterized by inflammation around the eyes — indicated treatment was substantially increasing the levels of low-density lipoprotein.

Low-density lipoprotein, or LDL, is a protein that helps to shuttle cholesterol throughout the body. LDL is sometimes called “bad cholesterol” because abnormally high levels are associated with a buildup of cholesterol in arteries and increased risk of heart disease.

After reviewing data form multiple clinical trials, Immunovant determined that LDL increases were related to IMVT-1401 in a dose-dependent manner — in other words, higher dosages of the medication led to greater increases in LDL levels. The company also determined that the increase in LDL likely was tied to a decrease in albumin, a protein that helps regulate the transport of cholesterol and other substances in the blood.

Increases in LDL and decreases in albumin were reversible, with their levels returning to normal once patients stopped taking IMVT-1401. No major heart-related adverse events have been reported in individuals taking IMVT-1401.

IMVT-1401 is designed to lower the levels of a type of antibody called immunoglobulin G (IgG). In MG and many other autoimmune diseases, IgG antibodies that erroneously target healthy tissues are the key drivers of disease.

Results from ASCEND MG (NCT03863080), a small Phase 2a clinical trial, indicated that treatment with IMVT-1401 safely reduced IgG levels and eased MG symptoms.

Notably, in the TED trial that prompted the halt in dosing, IMVT-1401 led to substantial reductions in IgG levels when given at weekly dosages of 255, 340, and 680 mg. In this trial, the lowest dose of IMVT-1401 (255 mg/week) did not cause the substantial changes in LDL or albumin levels that were seen for the higher doses.

Participants in various IMVT-1401 clinical trials who also were taking cholesterol-lowering medications called statins had “only minimal LDL increases” across a variety of doses, according to Immunovant.

“These results present an opportunity for flexibility in dosing, dose intervals, and a lower-volume injection to explore in our future clinical trials,” Salzmann said.

Results from the TED trial showed no significant effect of IMVT-1401 on the main measures of treatment efficacy. Yet, because the trial was halted halfway through, there were fewer participants available for efficacy assessments — a total of 41, instead of the planned 77. In a statistical sense, this means that the sample size was too small to yield a statistically reliable result.

Immunovant also announced the appointment of a new chief medical officer: William (Bill) Macias, MD, PhD.

“We are thrilled to consolidate full scientific and development leadership under Bill. His impressive breadth of experience and proven track record of clinical development in numerous therapeutic areas fits very well with the potential of IMVT-1401 across multiple indications,” Salzmann said.