Biohaven Ltd. (NYSE: BHVN) has announced promising Phase 1 data for BHV-1400, a next-generation Targeted Removal of Aberrant Protein (TRAP) degrader, in patients with IgA nephropathy (IgAN). The results, presented at the 43rd Annual J.P. Morgan Healthcare Conference, highlight the potential of BHV-1400 to selectively lower aberrant galactose-deficient IgA1 (Gd-IgA1), the antibody implicated in IgAN, while preserving normal IgA levels.
The Phase 1 study demonstrated that the first and lowest dose tested (125mg) of BHV-1400 achieved a median reduction of 60% in Gd-IgA1 within four hours of administration. Maximal reductions exceeding 70% were observed within eight hours, and these reductions were sustained for days after a single dose. This rapid reduction is unprecedented among drugs targeting Gd-IgA1.
Selective Immunoglobulin Lowering
BHV-1400's mechanism of action offers a selective approach to immunoglobulin lowering, potentially mitigating the safety risks associated with complement inhibition or broad antibody suppression. The Phase 1 study reported no clinically significant changes in innate or adaptive immunity, including white blood cells and immunoglobulins IgG, IgA, IgE, and IgM. There were also no clinically significant reductions in albumin, liver function test abnormalities, or increases in cholesterol compared to baseline.
Clinical Implications and Future Development
IgA nephropathy is a rare chronic kidney disease affecting young and middle-aged adults, and it can lead to kidney failure in up to 40% of patients within 10-20 years. The current treatment landscape involves managing symptoms and slowing disease progression, but there is a need for therapies that target the underlying cause of the disease. Biohaven plans to initiate a pivotal trial in IgAN using an accelerated regulatory path upon completion of the Phase 1 trial.
According to Tova Gardin, M.D., M.P.P, Biohaven Chief Translational Officer, the results of BHV-1400 highlight the speed, precision, and patient-centered innovation that drives development of each of Biohaven's molecules. She stated that lowering Gd-IgA1 by 60% within hours of dose administration realizes the precision possible with MoDE degraders, offering the possibility of selectively degrading the pathogenic driver of disease while leaving host immunity unperturbed.
Broader Portfolio Progress
Biohaven also provided updates on other programs, including BHV-1300 for IgG-mediated diseases and BHV-1600 for peripartum cardiomyopathy (PPCM). BHV-1300, administered subcutaneously, achieved deep reductions of targeted IgG, with reductions greater than 60% in the lowest dose cohort of the multiple ascending dose (MAD) study. BHV-1600 has been well-tolerated in Phase 1 and has received FDA alignment for a study design to potentially pursue an accelerated approval pathway in PPCM.
These advancements underscore Biohaven's commitment to developing innovative therapies for a range of rare and common diseases, leveraging its Molecular Degrader of Extracellular Proteins (MoDE) platform to address unmet medical needs in immunology, neuroscience, and oncology.
