Treatment for Graves’ Disease Has Stalled for Over 60 Years… Competition to Target the ‘Cause of the Disease’ Begins Graves’ disease

is an autoimmune disorder in which the immune system produces autoantibodies that stimulate the thyroid-stimulating hormone receptor (TSHR), causing the thyroid to secrete excessive amounts of thyroid hormone. It is the most common cause of hyperthyroidism and causes symptoms such as increased heart rate, weight loss, hand tremors, and fatigue. In some patients, it is accompanied by thyroid-eye disease (TED), which involves inflammation of the tissue around the eyes and protrusion of the eyeballs.

Treatment methods have not changed significantly since the 1950s and 1960s. Currently, antithyroid drugs (ATDs), which suppress thyroid hormone production, are the first-line treatment; if the condition cannot be controlled with medication, radioactive iodine is used to destroy thyroid tissue, or the thyroid is surgically removed. Conventional treatments work by suppressing excessive hormone secretion or removing the thyroid gland itself; they do not directly target the autoantibodies that cause the disease.

Another limitation is that even after 12 to 18 months of antithyroid drug therapy, the condition recurs in about half of patients after treatment is discontinued. If radioactive iodine or thyroidectomy is chosen, a significant number of patients must take thyroid hormone replacement therapy for the rest of their lives. Since the course of the disease and autoantibody levels vary from patient to patient, and the dosage of antithyroid drugs must be adjusted during clinical trials, it is difficult to distinguish the drug’s intrinsic efficacy. However, Royvant reports that by applying strict evaluation criteria—which include restoring normal thyroid function and discontinuing antithyroid medication—it is possible to account for placebo responses resulting from spontaneous remission.

The market potential is significant. Immunovant estimates that there are approximately 880,000 patients with Graves’ disease in the United States. Of these, the company identifies approximately 330,000 patients—who have experienced a relapse after antithyroid drug therapy but have not opted for thyroid-removing treatments such as surgery or radioactive iodine—as the potential target population for IMVT-1402. Given that the existing market is centered on low-cost antithyroid drugs, radioactive iodine, and surgery, the market size is likely to grow even further following the launch of this high-cost targeted therapy.

IMVT-1402 works by blocking FcRn to reduce immunoglobulin G (IgG) and disease-causing autoantibodies in the blood. Unlike existing drugs that merely suppress thyroid hormone production, it targets the root cause of the disease with the goal of maintaining remission even after treatment is completed. In a previous Phase 2 clinical trial of batoclimab, a significant number of patients maintained normal thyroid function without antithyroid medication even six months after the end of treatment, and their levels of thyroid-stimulating hormone receptor antibodies (TRAb) remained reduced. In one of these trials, patients received 600 mg once weekly for up to 52 weeks, while another trial compared 600 mg, 300 mg, and a placebo over 26 weeks. Both trials primarily evaluate the proportion of patients who maintain normal thyroid function without antithyroid medication.

Competition has also begun. ArgenX, a leader in the FcRn field, is developing efgartigimod—the active ingredient in “Vibgart”—as a treatment for Graves’ disease and initiated two Phase 3 clinical trials for Graves’ disease last June. Like IMVT-1402, it works by blocking FcRn to reduce pathogenic IgG, making it the most direct competitor. Although both companies have entered late-stage clinical trials, IMVT-1402 is ahead in terms of clinical trial initiation and expected topline results.

Candidates that directly block TSHR are also emerging. Viridian Therapeutics plans to submit an investigational new drug application (IND) in the fourth quarter of this year for a subcutaneous anti-TSHR antibody targeting Graves’ disease and thyroid eye disease (TED). Escerial Bio also plans to begin the first human clinical trial of its anti-TSHR antibody, ETHY-001, in the second half of this year. Unlike FcRn inhibitors, which lower total IgG levels, TSHR antibodies are designed to selectively block TSHR activation—the direct cause of Graves’ disease. However, as they are still in the early stages of development, their superiority in efficacy and safety compared to FcRn inhibitors must be confirmed in clinical trials.

Matt Glain, CEO of Royvant, said in a recent conference call, “We will enter the market much earlier than other companies,” adding, “As a first-mover, we can influence the treatment paradigm and provide patients and healthcare professionals with a new treatment option before any other alternatives become available.” He went on to express confidence in the first-mover advantage, noting, “Graves’ disease is not about beating a specific competitor, but about creating a new market in an indication with significant unmet need.”

An official from HANALL BIOPHARMA CO.,LTD said, “Currently, imerofubate is being developed with the priority of commercializing it for Graves’ disease by 2028,” adding, “Although the market targets approximately 330,000 patients in the U.S. alone, there are no approved treatments in the same class; therefore, if commercialized, it has the potential to become the first-in-class and best-in-class new drug.” The official further emphasized, “Hanol will receive a milestone payment upon approval of the marketing authorization for Graves’ disease.”