Biohaven Reports Positive Degrader Data Achieving > 80% Sustained Reductions in Total IgG with Potential First-in-Class BHV-1300
Biohaven (NYSE: BHVN) has reported positive Phase 1 data for BHV-1300, a potential first-in-class IgG1,2,4 selective degrader. The subcutaneous administration achieved up to 84% reduction in total IgG with a median reduction of 80% after weekly 1000 mg dosing.
BHV-1300 demonstrated rapid, deep, and sustained reductions in IgG levels within hours of each weekly dose. The drug was well-tolerated up to 2000 mg doses with mostly mild, self-resolving adverse events and no serious safety concerns. The treatment specifically targets IgG1,2,4 while sparing IgG3, maintaining key immune defenses.
Based on these results, Biohaven plans to initiate a Phase 2 study in Graves' disease in mid-2025. Graves' disease affects 3 million people in the US and 80 million globally. The company's MoDE™ technology allows for customization of IgG lowering across different disease indications.
Biohaven (NYSE: BHVN) ha riportato dati positivi della Fase 1 per BHV-1300, un potenziale degrader selettivo di IgG1,2,4. L'amministrazione sottocutanea ha raggiunto fino a un 84% di riduzione totale delle IgG con una riduzione mediana dell'80% dopo somministrazioni settimanali di 1000 mg.
BHV-1300 ha dimostrato riduzioni rapide, profonde e sostenute dei livelli di IgG entro poche ore da ciascuna dose settimanale. Il farmaco è stato ben tollerato fino a dosi di 2000 mg, con eventi avversi per lo più lievi e autolimitanti e nessuna preoccupazione seria per la sicurezza. Il trattamento mira specificamente a IgG1,2,4 risparmiando IgG3, mantenendo così le difese immunitarie chiave.
In base a questi risultati, Biohaven prevede di avviare uno studio di Fase 2 sulla malattia di Graves a metà del 2025. La malattia di Graves colpisce 3 milioni di persone negli Stati Uniti e 80 milioni a livello globale. La tecnologia MoDE™ dell'azienda consente la personalizzazione della riduzione delle IgG attraverso diverse indicazioni patologiche.
Biohaven (NYSE: BHVN) ha informado datos positivos de la Fase 1 para BHV-1300, un posible degradador selectivo de IgG1,2,4. La administración subcutánea logró hasta un 84% de reducción en el total de IgG con una reducción mediana del 80% después de dosis semanales de 1000 mg.
BHV-1300 demostró reducciones rápidas, profundas y sostenidas en los niveles de IgG dentro de unas pocas horas después de cada dosis semanal. El fármaco fue bien tolerado hasta dosis de 2000 mg, con eventos adversos mayormente leves y autolimitados, sin preocupaciones serias de seguridad. El tratamiento se dirige específicamente a IgG1,2,4 mientras preserva IgG3, manteniendo las defensas inmunitarias clave.
Basado en estos resultados, Biohaven planea iniciar un estudio de Fase 2 en la enfermedad de Graves a mediados de 2025. La enfermedad de Graves afecta a 3 millones de personas en EE. UU. y 80 millones a nivel mundial. La tecnología MoDE™ de la empresa permite la personalización de la reducción de IgG en diferentes indicaciones de enfermedad.
Biohaven (NYSE: BHVN)은 BHV-1300에 대한 긍정적인 1상 데이터를 발표했습니다. 이는 잠재적인 최초의 IgG1,2,4 선택적 분해제입니다. 피하 투여는 총 IgG의 84% 감소를 달성했으며, 주당 1000mg 투여 후 중간 감소율은 80%입니다.
BHV-1300은 매주 투여 후 몇 시간 이내에 IgG 수치를 빠르고 깊게 지속적으로 감소시키는 것을 보여주었습니다. 이 약물은 2000mg까지 잘 견뎌졌으며, 대부분 경미하고 자가 해결되는 부작용이 있었고 심각한 안전 문제는 없었습니다. 이 치료는 IgG3를 보존하면서 IgG1,2,4를 특정적으로 타겟합니다.
이 결과를 바탕으로 Biohaven은 2025년 중반에 그레이브스병에 대한 2상 연구를 시작할 계획입니다. 그레이브스병은 미국에서 300만 명, 전 세계적으로 8000만 명에게 영향을 미칩니다. 회사의 MoDE™ 기술은 다양한 질병 지표에 따라 IgG 감소를 맞춤화할 수 있게 해줍니다.
Biohaven (NYSE: BHVN) a rapporté des données positives de Phase 1 pour BHV-1300, un potentiel dégradateur sélectif de classe IgG1,2,4. L'administration sous-cutanée a atteint jusqu'à 84% de réduction de l'IgG total avec une réduction médiane de 80% après des doses hebdomadaires de 1000 mg.
BHV-1300 a montré des réductions rapides, profondes et durables des niveaux d'IgG dans les heures suivant chaque dose hebdomadaire. Le médicament a été bien toléré jusqu'à des doses de 2000 mg, avec principalement des événements indésirables légers et autolimités, sans préoccupations sérieuses de sécurité. Le traitement cible spécifiquement IgG1,2,4 tout en épargnant IgG3, maintenant ainsi les défenses immunitaires clés.
Sur la base de ces résultats, Biohaven prévoit de lancer une étude de Phase 2 sur la maladie de Graves à la mi-2025. La maladie de Graves touche 3 millions de personnes aux États-Unis et 80 millions dans le monde. La technologie MoDE™ de l'entreprise permet de personnaliser la réduction des IgG selon différentes indications de maladie.
Biohaven (NYSE: BHVN) hat positive Phase-1-Daten für BHV-1300, einen potenziellen selektiven Degrader von IgG1,2,4, veröffentlicht. Die subkutane Verabreichung erreichte eine Reduktion des Gesamt-IgG um bis zu 84% mit einer medianen Reduktion von 80% nach wöchentlichen Dosen von 1000 mg.
BHV-1300 zeigte innerhalb weniger Stunden nach jeder wöchentlichen Dosis schnelle, tiefe und nachhaltige Reduktionen der IgG-Spiegel. Das Medikament wurde bis zu Dosen von 2000 mg gut vertragen, mit überwiegend milden, selbstlimitierenden unerwünschten Ereignissen und ohne ernsthafte Sicherheitsbedenken. Die Behandlung zielt spezifisch auf IgG1,2,4 ab und schont IgG3, wodurch die wichtigen Immunabwehrmechanismen erhalten bleiben.
Basierend auf diesen Ergebnissen plant Biohaven, eine Phase-2-Studie zur Graves-Krankheit Mitte 2025 zu starten. Die Graves-Krankheit betrifft 3 Millionen Menschen in den USA und 80 Millionen weltweit. Die MoDE™-Technologie des Unternehmens ermöglicht die Anpassung der IgG-Reduktion über verschiedene Krankheitsindikationen hinweg.
- Achieved 84% reduction in total IgG with 80% median reduction
- Demonstrated rapid and sustained efficacy within hours
- Well-tolerated safety profile up to 2000 mg doses
- Selective targeting mechanism preserving immune defense
- Large addressable market of 80M patients globally
- Phase 2 trials won't start until mid-2025
- Still in early clinical development phase
- Requires weekly dosing administration
Insights
Biohaven's positive Phase 1 data for BHV-1300 represents a significant clinical milestone with material implications for the company's growth trajectory. The reported 80-84% reduction in IgG levels positions this drug candidate favorably against existing FcRn inhibitors in development, which typically achieve 60-70% reductions. This efficacy advantage could translate to meaningful market differentiation.
The Graves' disease target market is substantial with 3 million patients in the US and 80 million globally, representing a multi-billion dollar opportunity. Current standards of care are to invasive thyroid removal, ablation, or antithyroid drugs with concerning side effect profiles, creating a clear market gap for novel approaches.
Beyond BHV-1300, Biohaven is advancing multiple assets from its MoDE platform including BHV-1400 for IgA nephropathy and BHV-1600 for cardiomyopathy, demonstrating pipeline depth. The partnership with Ypsomed AG for autoinjector technology enhances commercial potential by enabling convenient self-administration.
While the data is promising, investors should recognize we're still in early clinical development with Phase 2 planned for mid-2025, suggesting potential commercialization remains years away. The safety profile appears clean thus far, a critical component for chronic autoimmune disease treatments.
The BHV-1300 data represents a potential paradigm shift in autoimmune disease treatment through a novel mechanism of selective extracellular protein degradation. The subcutaneous administration achieving 80-84% IgG reduction is technically impressive and clinically meaningful compared to current therapeutic approaches.
The selective degradation of IgG1,2,4 while sparing IgG3 is particularly noteworthy from an immunological perspective. This selectivity profile maintains protection against viral, bacterial and parasitic infections (primarily mediated by IgG3) while specifically targeting the IgG1 autoantibodies that drive Graves' disease pathology by stimulating the TSH receptor.
The rapid onset of action ("within hours of each dose") represents a key advantage over monoclonal antibody approaches which typically require longer to achieve maximum effect. Furthermore, the tunable nature of BHV-1300's IgG reduction through dose adjustment creates flexibility for treating various autoimmune conditions with different target IgG levels.
The preservation of other immunoglobulin classes (IgA, IgE, IgM) during treatment suggests a favorable immunological safety profile compared to broader immunosuppressive approaches, potentially reducing infection risks while maintaining therapeutic efficacy against the autoimmune driver.
- Optimized subcutaneous administration of BHV-1300 achieved rapid, deep and sustained lowering of IgG, differentiating Biohaven's new small molecule class of degraders from the monoclonal antibody FcRn-targeting competition.
- Up to
84% reduction of total IgG was observed with a median reduction of80% after subcutaneous weekly 1000 mg dosing in the ongoing Phase 1 study. - Subcutaneous BHV-1300 achieved progressive reductions in IgG levels within hours of each weekly dose administration, and pharmacodynamic effects were sustained compared to baseline over the four-week period.
- Dose escalation with BHV-1300 continues in the study and plans to explore deeper reductions to characterize the potential range of targeted IgG lowering possible with Biohaven's MoDE™ technology, allowing for the customization of speed and depth of IgG lowering and decreased frequency of administration across different disease indications.
- BHV-1300 was rationally designed to selectively target IgG1,2,4 while sparing IgG3. Retaining IgG3 allows for preservation of key host immune defense against viruses, bacteria and parasites.
- Up to
- BHV-1300 has been safe and well tolerated across the ongoing Phase 1 studies with subcutaneous doses now administered up to 2000 mg.
- Most adverse events (AEs) were mild and self-resolving, there were no discontinuations due to AEs related to study drug, and there were no serious or severe AEs.
- There were no clinically significant increases in ALT/AST or bilirubin, no clinically significant reductions in albumin and no clinically significant increases in cholesterol compared to placebo over the 4-week dosing period.
- There were no clinically significant reductions in other immunoglobulins including IgG3, IgA, IgE, or IgM compared to baseline.
- Based upon the rapid and deep reductions of total IgG observed with subcutaneous BHV-1300, Biohaven reiterates its plans to initiate a Phase 2 study in Graves' disease in mid-2025. Additional follow-on studies in other autoimmune diseases will be pursued.
- Graves' disease is a common autoimmune disorder affecting 3 million individuals in the US and 80 million people globally. Graves' disease is caused by IgG1 autoantibodies that hyper-stimulate the thyroid stimulating hormone (TSH) receptor. The rational design of BHV-1300 enables degradation of the autoantibodies causing Graves' disease, known to be of the IgG1 subclass, while maintaining host immunity.
- TRAPTM degraders, Biohaven's next generation "targeted removal of aberrant protein" degraders from the MoDE platform also continue to advance through Phase 1 with multiple doses completing the SAD/MAD cohorts including BHV-1400, a selective Gd-IgA1 degrader being developed for IgA nephropathy, and BHV-1600, a β1AR autoantibody degrader for cardiomyopathy. Additional details and data regarding these TRAP degraders will be presented at an upcoming conference.
In the four-week Phase 1 study, subcutaneously administered BHV-1300 at a dose of 1000 mg weekly achieved rapid, deep and sustained reductions in total IgG of up to
Tova Gardin, MD, MPP, Chief Translational Officer at Biohaven, commented, "BHV-1300 has demonstrated remarkable efficacy in deep lowering of total IgG, leveraging the groundbreaking technology of the MoDE platform, to potentially revolutionize treatment of patients with autoimmune disease. Biohaven's unique extracellular degrader technology leverages the body's natural hepatic clearance mechanism to remove targeted antibodies contributing to disease and promises to usher in a new era of tunable, selective and self-administered immune therapy."
BHV-1300 was safe and well-tolerated in subcutaneous doses up to 2000 mg with no clinically significant increases in ALT, AST, or bilirubin, no clinically significant reductions in albumin, and no clinically significant increases in cholesterol over the four-week dosing period compared to placebo. There were no clinically significant reductions in IgG3, IgA, IgE, or IgM compared to baseline. Most AEs were mild and self-resolving, there were no discontinuations due to AEs related to study drug, and there were no serious or severe AEs. The Phase 1 study is ongoing with plans to continue to escalate multiple doses to explore the full range of targeted IgG lowering possible with this technology to customize an ideal treatment approach for different disease indications.
Biohaven's MoDE technology used in developing BHV-1300 was licensed from Yale University stemming from groundbreaking chemistry work in the Spiegel Lab. Yale Professor David Spiegel, MD, PhD, inventor of the MoDE technology and the first to patent the use of targeted extracellular protein degraders that utilize the asialoglycoprotein receptor (ASGPR), commented, "This remarkable demonstration in humans of rapid, deep and sustained reductions of targeted IgG removal with BHV-1300 is a breakthrough and a testament to the scientific advancements that can be accomplished by innovative academic and industry collaborations. BHV-1300 has catapulted the field of extracellular degraders forward and promises to shift the paradigm for the treatment of individuals living with immune-mediated diseases. It is truly an honor to be able to collaborate with the team at Biohaven on this exciting journey."
BHV-1300 is differentiated from monoclonal antibodies targeting FcRn inhibition, offering a novel and selective approach to treat autoimmune causes of disease, while enabling patients to maintain immune protection against infection through preservation of IgG3 (Figure 2). IgG degradation with BHV-1300 is deep and tunable, capable of achieving remarkable depth of IgG lowering, and with refinement in degradation depth feasible through titration of dose level and frequency. It is designed for self-administration via an easy-to-use and patient-friendly autoinjector through an ongoing partnership with Ypsomed AG.
Dr. Gardin added, "This data released today supports advancing BHV-1300 as a potential first-in-class, small molecule approach to treating Graves' disease, a common autoimmune disease that is currently treated with surgery, ablation or anti-thyroid drugs. Our innovative approach unifies cutting-edge science with renewed understanding of disease pathology, to advance a potential first and best-in-class therapeutic for the treatment of Graves' disease. Based on the PK/PD and safety profiles exhibited in the ongoing Phase 1 study, we are thrilled to advance BHV-1300 forward as we aim to disrupt the current treatment paradigm in Graves' disease and potentially revolutionize the treatment of this disease which impacts millions of patients across the world."
Graves' disease is an autoimmune condition that impacts 3 million individuals in the US and 80 million people worldwide. In Graves' disease (Figure 3), IgG1 autoantibodies mimic TSH, binding the TSH receptor in the thyroid and stimulating excess production of thyroid hormones. Graves' disease impacts every organ system, causing symptoms such as cardiac arrhythmias, anxiety, heat intolerance, weight loss, changes in appetite and bowel movements and shortness of breath, in addition to causing related conditions of thyroid eye disease and infiltrative dermopathy. A considerable unmet need exists for improved therapeutic options that target the underlying autoimmune etiology of disease and do not result in permanent hypothyroidism or bear risk of fatal agranulocytosis, hepatotoxicity and teratogenicity. While conventional treatments for Graves' disease, including thyroid removal or ablation and antithyroid drugs, have not changed in 70 years, scientific understanding of immunobiology has advanced considerably, enabling the development of BHV-1300, a precision therapeutic that targets the underlying IgG1 autoantibodies causing the disease.
About BHV-1300
BHV-1300 is a small molecule and potential first-in-class 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 the disease. BHV-1300 spares IgG3 to preserve patient immune protection against bacteria, viruses and parasites (Figure 2). The results of the ongoing Phase 1 study confirm that BHV-1300 produces deep reductions in total IgG, is selective, sparing IgG3, is tunable, and is safe and well-tolerated.
About Biohaven
Biohaven is a biopharmaceutical company focused on the discovery, development, and commercialization of life-changing treatments in key therapeutic areas including immunology, neuroscience and oncology. The company is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. For more information, visit www.biohaven.com.
Forward-looking Statements
This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate", "potential first-in-class", "disrupt", "potentially revolutionize", "groundbreaking", "potential first and best-in-class" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable US regulatory requirements; the potential commercialization of Biohaven's product candidates; and the effectiveness and safety of Biohaven's product candidates. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission, including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this news release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
MoDE and TRAP are trademarks of Biohaven Therapeutics Ltd.
Investor Contact:
Jennifer Porcelli
Vice President, Investor Relations
jennifer.porcelli@biohavenpharma.com
+1 (201) 248-0741
Media Contact:
Mike Beyer
Sam Brown Inc.
mikebeyer@sambrown.com
+1 (312) 961-2502
View original content to download multimedia:https://www.prnewswire.com/news-releases/biohaven-reports-positive-degrader-data-achieving--80-sustained-reductions-in-total-igg-with-potential-first-in-class-bhv-1300-302389515.html
SOURCE Biohaven Ltd.
FAQ
What are the key efficacy results of BHV-1300 in the Phase 1 trial?
When will Biohaven (BHVN) start Phase 2 trials for BHV-1300 in Graves' disease?
What safety profile did BHV-1300 demonstrate in Phase 1 trials?
How does BHV-1300's mechanism differ from current Graves' disease treatments?
What is the market potential for BHV-1300 in Graves' disease treatment?
