Biohaven Starts Pivotal Phase 3 Trial of BHV-1300, the First Extracellular Protein Degrader for Graves’ Disease

Biohaven has initiated the pivotal Phase 3 clinical trial of BHV-1300 (NCT07661056) after enrolling the first patient with Graves’ disease. The investigational therapy is the first extracellular protein degrader to advance into a pivotal study and represents a new therapeutic strategy that targets the autoimmune cause of Graves’ disease rather than the thyroid gland itself.

The randomized, double-blind, placebo-controlled trial will enroll approximately 300 adults with Graves’ disease. The primary endpoint is restoration of normal thyroid function at 26 weeks without the use of antithyroid medication. BHV-1300 is administered by subcutaneous injection through a self-administered autoinjector intended for at-home use.

First MoDE Therapy Targets Disease-Causing Autoantibodies

BHV-1300 is the lead candidate from Biohaven’s MoDE™ (Molecular Degraders of Extracellular proteins) platform, licensed exclusively from Yale University. Unlike conventional therapies that suppress thyroid hormone production or permanently destroy thyroid tissue, BHV-1300 selectively eliminates the TSH receptor (TSHR)-IgG1 autoantibody, the underlying driver of Graves’ disease.

The small-molecule degrader harnesses the body’s natural hepatic clearance pathways to remove pathogenic IgG1, IgG2, and IgG4 antibodies while preserving IgG3, an antibody subclass that plays an important role in protecting against bacterial, viral, and parasitic infections.

This mechanism also distinguishes BHV-1300 from FcRn inhibitors by avoiding accelerated clearance of therapeutic biologics and reducing risks associated with class-related adverse effects such as cholesterol elevation, albumin reduction, and headache.

Phase 1 Data Supported Advancement to Phase 3

The pivotal program is supported by Phase 1b and expansion study results showing robust biological and early clinical activity.

Investigators reported:

• More than 80% reduction in pathogenic TSHR autoantibodies
• Rapid normalization of free T4 and free T3 levels in patients with Graves’ hyperthyroidism
• Improvement in hallmark symptoms of Graves’ disease
• Preservation of IgG3, IgA, IgM, and IgE
• Favorable safety and tolerability

Across Biohaven’s MoDE and TRAP™ extracellular degrader programs, nearly 200 participants have received treatment in Phase 1 studies. Most reported adverse events were mild and resolved without intervention.

Potential Shift in Graves’ Disease Treatment

Graves’ disease affects approximately 1% of the global population and remains the leading cause of hyperthyroidism. Despite the substantial disease burden, no new therapy has been approved for the condition in more than 70 years. Current treatment options, including antithyroid drugs, radioactive iodine, and thyroidectomy, control thyroid hormone excess but do not eliminate the autoimmune antibodies responsible for disease progression. The same pathogenic antibody also contributes to thyroid eye disease, pretibial myxedema, and neonatal Graves’ disease.

According to Beth Emerson, Executive Medical Director at Biohaven and lead investigator for the clinical program, BHV-1300 has the potential to introduce a disease-modifying approach by targeting the underlying autoimmune process rather than its downstream consequences.

Tova Gardin, Chief Translational Officer at Biohaven, said the Phase 3 study represents an important step for the company’s extracellular protein degrader platform and could support future development of BHV-1300 in additional IgG-mediated autoimmune diseases.

Regulatory Path Forward

Successful completion of the Phase 3 trial could establish BHV-1300 as the first approved extracellular protein degrader and the first new therapeutic option for Graves’ disease in decades. Beyond Graves’ disease, Biohaven plans to expand its MoDE and TRAP extracellular degrader platforms into other antibody-mediated autoimmune disorders, broadening the potential application of this emerging class of precision immunology therapies.

Reference

Biohaven Advances a New Class of Precision Immunology Therapies: First MoDE Extracellular Protein Degrader, BHV-1300, Begins Phase 3 Pivotal Trial in Graves’ Disease | Biohaven, Ltd.