공시 • Dec 16
Biohaven Ltd. Reports Positive Phase 1 Degrader Data, Achieving Deep Targeted IgG Reductions in the Lowest Subcutaneous Dose Tested
Biohaven Ltd. highlighted the achievement of several clinical and regulatory milestones across its proprietary Molecular Degrader of Extracellular Proteins (MoDE™) platform as well as its glutamate modulation and ion channel programs. Subcutaneously administered BHV-1300 achieved deep lowering of targeted IgG, with reductions > 60% in the lowest subcutaneous dose tested in the ongoing multiple ascending dose (MAD) study. Subcutaneous BHV-1300 achieved progressive reduction in IgG within hours of each weekly dose administration in the MAD, and pharmacodynamic effects were sustained relative to baseline over the four-week study period. BHV-1300 has been safe and well-tolerated across the Phase 1 study. There were no clinically significant effects on albumin or liver function, and no increases in cholesterol were noted. Further enhancing the competitive safety profile and as intentionally designed, plasma IgG3 levels were preserved through the end of study week 4 to allow for healthy immune effector functioning. All AEs were mild, any drug-related AE resolved, and there were no discontinuations due to study drug related AEs. The optimized subcutaneous formulation in the MAD also showed substantially less inter-patient variability compared to previously reported intravenous BHV-1300. Escalating dose level cohorts of subcutaneous BHV-1300 are ongoing to explore the full range of IgG reductions possible with BHV-1300 for a wide range of future disease indications. In addition to the new Phase 1 data with BHV-1300, Biohaven also announced regulatory acceptance of three INDs and/or CTAs for its next-generation MoDE molecules to target other immune mediated diseases. Two of these novel MoDEs, BHV-1400 and BHV-1600, represent the platform's first autoantibody specific degraders, sparing the body's healthy antibodies (IgG, IgA, etc.) to function normally while clearing disease-causing antibodies. Dosing in humans has been initiated for BHV-1400, a novel IgA nephropathy (IgAN) investigational therapy designed to selectively degrade galactose deficient IgA1 (Gd-IgA1) without immunosuppression. IgAN is a rare disease affecting approximately 60,000 individuals in the United States. It is often diagnosed in the second or third decade of life, progresses over decades, and can result in kidney failure leading to the need for hemodialysis. Approved therapies broadly suppress the immune system or target the downstream consequences of immune damage without targeting the autoimmune cause of disease. For a disease which is diagnosed in young adults and treatment may be required over the lifespan, BHV-1400 is highly differentiated, engineered to clear the pathogenic nidus of disease, Gd-IgA1, and preserve the individual's immunoglobulins (IgG, IgA, IgE, IgM), immune cells, and complement system. Thus, BHV-1400 is expected to result in less potential for respiratory, mucosal or central nervous system infections compared to broader IgA lowering or immunosuppressive strategies in development. Additionally, IgAN clinical trials have a well-established pathway for accelerated approval. Biohaven also initiated dosing in humans with BHV-1600 in Fourth Quarter 2024. BHV-1600 is a MoDE engineered to rapidly degrade pathogenic autoantibodies to the b1-adrenergic receptor (b1AR). BHV-1600 is the first rationally designed investigative treatment in development for peripartum cardiomyopathy (PPCM), a rare type of heart failure that occurs during pregnancy or soon after birth that has no currently approved therapy. In b1AR autoantibody-driven cardiomyopathy, autoantibodies bind b1AR and induce cardiomyocyte toxicity and heart failure (Figure 3). PPCM affects mothers at an incredibly vulnerable period: previously healthy, individuals with PPCM develop profound heart failure, struggling with new symptoms as their child experiences its first days and often first years of life. Without disease-specific therapies, women with PPCM can develop heart failure and may emergently require left ventricular assistive devices or heart transplant. Given PPCM is a life-threatening disease with no current treatment and the potential for BHV-1600 to rapidly degrade pathogenic b1AR autoantibodies, Biohaven completed an INTERACT meeting with the FDA in Fourth Quarter 2024 and gained alignment on a clinical development program to pursue an accelerated approval pathway for BHV-1600 in PPCM. An IND has also been accepted for BHV-1310, an optimized and selective IgG1, IgG2, and IgG4 degrader. Dosing is expected in humans in first quarter 2025. In addition to key updates in the MoDE clinical development program, Biohaven also announced critically important advances related to its late-stage glutamate and ion channel platforms. A new drug application (NDA) was submitted to the US FDA for troriluzole in the treatment of all genotypes of spinocerebellar ataxia (SCA), following the completion of a pre-NDA meeting in fourth quarter 2024. Troriluzole was previously granted Orphan Drug and Fast-Track designations by FDA, and qualifies for potential Priority Review. Biohaven recently reported positive topline pivotal results in SCA in September 2024, demonstrating that troriluzole slowed disease progression by 50-70% over the 3-year study period. SCA is a rare, life-threatening, progressively debilitating neurodegenerative disease that affects approximately 15,000 people in the US, and 24,000 in Europe and the United Kingdom. Troriluzole has been safe and well-tolerated in over 8 years of clinical trial experience. There are no FDA approved treatments for SCA and troriluzole is the first investigational agent to show disease slowing in its clinical development program. Biohaven further announced the completion of enrollment in a pivotal BHV-7000 Phase 2/3 trial in bipolar disorder in fourth quarter 2024. BHV-7000 is a selective activator of Kv7 potassium channels that offers a novel and compelling mechanism of action for the treatment of bipolar disorder and an excellent tolerability at all doses evaluated in previous studies without the central nervous system adverse effects, such as somnolence and other CNS-related effects, that typically limit the use of other mood stabilizing medications. The trial completed enrollment several months ahead of anticipated timelines, reflecting the high unmet need for new treatments in bipolar disorder. The Phase 2/3 double-blind, placebo-controlled study enrolled approximately 256 patients. Patients were randomized to receive BHV-7000 75 mg once daily or placebo over a 3-week treatment period. The primary outcome measure of the study is the change from baseline to week 3 in mania symptom severity, as measured by the Young Mania Rating Scale (YMRS). Secondary objectives include response and remission rates, early onset of efficacy, depression symptom severity as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), and safety.
