공시 • May 30
Biohaven Reports Positive Clinical Biomarker and Patient Data for Bhv-1300 and Bhv-1400 in Graves' Disease and Iga Nephropathy
Biohaven reported compelling results regarding its proprietary extracellular MoDE (BHV-1300) and TRAP (BHV-1400) degrader platform. BHV-1300 demonstrated deep, rapid, and sustained lowering of pathogenic TSHR autoantibodies (TSHR-IgG1) in patients with Graves' hyperthyroidism receiving 1000 mg SC weekly, with mean reductions in TSHR-IgG1 exceeding >80% over the 12-week study. Participants with Graves' overt hyperthyroidism, confirmed by elevated baseline thyroid tests despite being treated with anti-thyroid drug therapy (ATD), experienced normalization of thyroid hormones within weeks; T4 normalization occurring at a median of 3 weeks and T3 at a median of 5 weeks after the first administration of BHV-1300. These preliminary patient data from an ongoing Phase 1b study highlight deep lowering of TSHR-IgG1 with BHV-1300 as a potentially disease-modifying approach to Graves' disease. Weekly administration of BHV-1300 1000 mg achieved mean reductions of pathogenic TSHR-IgG1 of >80% by week 12 in patients with Graves' hyperthyroidism, a deeper reduction in pathogenic TSHR-IgG1 than has been demonstrated with the FcRn inhibitor competition. Patients with elevated thyroid hormones experienced a normalization of free T4 at a median of 3 weeks and a normalization of free T3 within a median of 5 weeks. Patients reported improvements in classic symptoms of hyperthyroidism including palpitations, fatigue, diarrhea, diaphoresis, tremor, and mood. BHV-1300 has been safe and well-tolerated through 12 weeks of dosing. Most AE's have been mild and self-resolving, there have been no drug-discontinuations, and no serious or severe AEs. There have been no clinically significant increases in cholesterol, decreases in albumin, or increases in ALT, AST or bilirubin. BHV-1300 preserved IgG3 and demonstrated no clinically significant reductions in IgG3, IgA, IgE, or IgM relative to baseline, maintaining the immune protection that FcRn inhibitors—which lower all IgG subclasses including IgG3—have not demonstrated. The positive Phase1b results in patients with Graves' disease who were hyperthyroid despite concurrent treatment with ATDs build on the observed dose-response relationship of BHV-1300 and literature that suggests deeper TSHR-IgG1 reductions are known to drive meaningfully higher efficacy compared to more modest lowering. Additional biomarker and pharmacokinetic data (n=8) regarding Graves' patients who were and were not hyperthyroid at baseline will be presented at the Biohaven R&D Day and will be available on the company's website. Based upon the pharmacokinetic and biomarker results with BHV-1300 in this Phase 1b study, Biohaven is advancing to a pivotal trial in Graves' disease in the coming weeks. The planned study design is a double-blind placebo-controlled study in adults with Graves' hyperthyroidism evaluating normalization of T3, T4, and TSH at 26 weeks absent an antithyroid drug. BHV-1300, first MoDE, is a small molecule, extracellular IgG degrader, rationally designed to leverage the body's natural hepatic clearance mechanisms to selectively target and remove IgG1, IgG2, and IgG4, the underlying cause of many immune-mediated diseases. BHV-1300 is mechanistically differentiated from FcRn inhibitors in multiple important ways: first, it selectively targets the disease-causing IgG subclasses (IgG1, IgG2, IgG4) while sparing IgG3, which mediates protection against bacteria, viruses, and parasites and which has not been demonstrated with FcRn inhibitors; second, as a small molecule, BHV-1300 does not interact with FcRn and therefore does not accelerate the clearance of co-administered Fc-containing biologic therapies—a meaningful clinical limitation of the FcRn inhibitor class; third, it avoids the off-target effects of cholesterol elevation, albumin reduction, and headache associated with first-generation FcRn inhibitors; and fourth, it is delivered in a convenient self-administered autoinjector. BHV-1400 achieved rapid, deep, selective, and sustained lowering of Gd-IgA1 in patients with IgA nephropathy (IgAN), differentiating Biohaven's leading TRAP degrader from the complement and BAFF/APRIL inhibitor competition. Participants with IgAN administered BHV-1400 showed a rapid, >60% mean reduction of Gd-IgA1 within hours, and a 70% mean reduction of within the first one-month of dosing. Observed reductions in Gd-IgA1 were deeper than has been reported with BAFF/APRIL inhibitors, APRIL-inhibitors, and CD38 inhibitors at these early time points. Preliminary observations also demonstrated an increase in eGFR, decrease in spot UPCR, and a decrease in hematuria with one month or less of dosing. BHV-1400 brings precision immunology to the treatment landscape of IgAN as it was rationally designed to selectively remove galactose-deficient IgA1 (Gd-IgA1), the pathogenic antibody driver of the disease while sparing healthy antibodies IgA, IgG, IgE, and IgM. Designed to target the disease driver while preserving healthy immunoglobulins, the complement system, and cell-mediated and humoral immunity, BHV-1400 offers a differentiated approach to current immunosuppressive therapies approved or in development. Administration of BHV-1400, the Company's first TRAP, galactose-deficient IgA1 (Gd-IgA1) TRAP degrader for the treatment of IgA nephropathy (IgAN) achieved deep, rapid, and sustained mean reductions of pathogenic Gd-IgA1 of >60% within 48 hours of subcutaneous administration and 70% within the one month of dosing in patients with IgAN. These reductions are deeper than those demonstrated by BAFF-APRIL inhibitors, APRIL inhibitors, and CD38 inhibitors at this early time point. Reductions in Gd-IgA1 were associated with resolution of hematuria, decreases in spot UPCR, and increases in eGFR. Participants also subjectively reported improvements in fatigue. BHV-1400 has been safe and well-tolerated throughout one month of dosing. Most AE's have been mild and self-resolving, there have been no drug-discontinuations, and no serious or severe AEs. There have been no clinically significant increases in ALT, AST or bilirubin, and no clinically significant reductions in other immunoglobulins relative to baseline. Effects were selective, with no clinically significant reductions observed in other immunoglobulins: IgA, IgG, IgE, or IgM.