Immunovant is set to initiate a late-stage clinical trial for its novel anti-FcRn agent, IMVT-1402, offering a potential new treatment avenue for Graves' disease, a condition affecting approximately 100,000 individuals annually in the U.S. The trial marks a significant step forward in addressing the unmet needs of patients who struggle with current treatment options.
Addressing Unmet Needs in Graves' Disease
Graves' disease, the leading cause of hyperthyroidism, presents with symptoms including shakiness, heart palpitations, anxiety, and poor sleep, significantly impacting patients' quality of life. Current treatments, such as methimazole, approved in the U.S. in 1950, often require high doses and may not achieve long-term remission, necessitating surgery or radioactive iodine therapy.
According to Immunovant CEO Peter Salzmann, M.D., an estimated 25% of Graves' disease patients fall into the difficult-to-treat category due to the condition's variability and the challenges in drug dosing. Mark Lupo, M.D., of the Thyroid & Endocrine Center of Florida, notes that patients often go undiagnosed for 6-12 months, during which they may be treated for anxiety or depression.
IMVT-1402: A Novel Approach
IMVT-1402 targets the neonatal Fc receptor (FcRn) to block the recycling of immunoglobulin G (IgG) autoantibodies, which, in Graves' disease, bind to and activate the thyroid-stimulating hormone (TSH) receptor, leading to excess thyroid hormone production. This approach aims to treat the disease upstream, addressing the root cause rather than just managing symptoms.
In a phase 2 proof-of-concept study with the first-generation anti-FcRn agent IMVT-1401 (batoclimab), Immunovant reported response rates exceeding 50% in treatment-resistant Graves' patients. While batoclimab effectively lowered IgG autoantibody levels, it also caused albumin reductions and increased lipids. IMVT-1402 has been reengineered to address these side effects.
Clinical Trial Design and Expectations
The upcoming global clinical trial will evaluate IMVT-1402, administered as a once-weekly subcutaneous injection. The goal is to establish a geographically distributed trial network to enroll a homogenous patient population. Salzmann anticipates that the demands of study participation will be a worthwhile tradeoff for patients who frequently visit their endocrinologists to adjust their methimazole dosage.
Lupo emphasizes that a treatment option directly addressing the cause of Graves' disease would be a significant paradigm shift, improving hyperthyroidism and thyroid eye disease control. Immunovant plans to include Graves' disease patients with eye symptoms in future trials, excluding those with severe eye disease initially for practical reasons.
Future Implications
Immunovant's broader vision includes targeting other autoimmune diseases driven by autoantibodies, such as myasthenia gravis and thyroid eye disease. The company aims to develop anti-FcRn medicines for at least 10 rare conditions, collectively representing an estimated 800,000 patients in the U.S.
Salzmann notes that the experience with batoclimab provided valuable insights into FcRn inhibition, dose response, and methimazole tapering. The IMVT-1402 registration program will involve two clinical studies prior to regulatory submission, with details available on ClinicalTrials.gov later this fall.
