Celldex Announces Barzolvolimab Met All Primary and Secondary Endpoints with High Statistical Significance in Positive Phase 2 Study in Chronic Inducible Urticaria
Celldex Therapeutics (NASDAQ:CLDX) announced positive Phase 2 clinical trial results for barzolvolimab in treating chronic inducible urticaria (CIndU). The study met all primary and secondary endpoints with high statistical significance in patients with cold urticaria and symptomatic dermographism who were unresponsive to antihistamines. The trial demonstrated significant improvements in both 150mg and 300mg dosing groups compared to placebo, with up to 53.1% of cold urticaria patients and 57.6% of symptomatic dermographism patients achieving complete response. The drug showed a favorable safety profile, with mostly Grade 1 adverse events. The company plans to advance to Phase 3 development in 2025.
Celldex Therapeutics (NASDAQ:CLDX) ha annunciato risultati positivi della fase 2 dello studio clinico per barzolvolimab nel trattamento dell'orticaria cronica inducibile (CIndU). Lo studio ha raggiunto tutti gli endpoint primari e secondari con alta significatività statistica in pazienti con orticaria da freddo e dermografismo sintomatico che non rispondevano agli antistaminici. Il trial ha dimostrato miglioramenti significativi sia nei gruppi di dosaggio da 150 mg che da 300 mg rispetto al placebo, con fino al 53,1% dei pazienti con orticaria da freddo e il 57,6% dei pazienti con dermografismo sintomatico che hanno ottenuto una risposta completa. Il farmaco ha mostrato un profilo di sicurezza favorevole, con eventi avversi per lo più di Grado 1. L'azienda prevede di passare allo sviluppo della fase 3 nel 2025.
Celldex Therapeutics (NASDAQ:CLDX) anunció resultados positivos de la fase 2 del ensayo clínico para barzolvolimab en el tratamiento de la urticaria crónica inducible (CIndU). El estudio alcanzó todos los objetivos primarios y secundarios con alta significación estadística en pacientes con urticaria por frío y dermografismo sintomático que no respondían a los antihistamínicos. El ensayo demostró mejoras significativas en los grupos de dosificación de 150 mg y 300 mg en comparación con el placebo, con hasta un 53,1% de los pacientes con urticaria por frío y un 57,6% de pacientes con dermografismo sintomático alcanzando una respuesta completa. El medicamento mostró un perfil de seguridad favorable, con eventos adversos en su mayoría de Grado 1. La compañía planea avanzar a la fase 3 en 2025.
셀덱스 테라퓨틱스 (NASDAQ:CLDX)는 만성 유발 두드러기(CIndU) 치료를 위한 바르졸볼리맙의 2상 임상 시험 결과가 긍정적이었다고 발표했습니다. 이 연구는 항히스타민제에 반응하지 않는 냉증 두드러기 및 증상성 피부 문지름 환자에서 높은 통계적 유의성을 가지고 모든 주요 및 보조 지표를 충족했습니다. 시험은 상당한 개선을 보여주었습니다 150mg 및 300mg 투여군에서 위약과 비교하여, 냉증 두드러기 환자의 최대 53.1%와 증상성 피부 문지름 환자의 57.6%가 완전한 반응을 보였습니다. 이 약물은 대부분 1등급 부작용으로 우호적인 안전성 프로파일을 보였습니다. 회사는 2025년에 3상 개발로 나아갈 계획입니다.
Celldex Therapeutics (NASDAQ:CLDX) a annoncé des résultats positifs d'un essai clinique de phase 2 pour le barzolvolimab dans le traitement de l'urticaire chronique induisible (CIndU). L'étude a atteint tous les objectifs principaux et secondaires avec une haute significativité statistique chez les patients présentant une urticaire froide et un dermographisme symptomatique qui ne répondaient pas aux antihistaminiques. L'essai a démontré des améliorations significatives dans les groupes de dosage de 150 mg et 300 mg par rapport au placebo, avec jusqu'à 53,1 % des patients souffrant d'urticaire froide et 57,6 % des patients atteints de dermographisme symptomatique atteignant une réponse complète. Le médicament a montré un profil de sécurité favorable, avec principalement des événements indésirables de grade 1. L'entreprise prévoit de passer au développement de phase 3 en 2025.
Celldex Therapeutics (NASDAQ:CLDX) gab positive Ergebnisse der Phase-2-Studie für Barzolvolimab zur Behandlung der chronischen induzierbaren Urtikaria (CIndU) bekannt. Die Studie erfüllte alle primären und sekundären Endpunkte mit hoher statistischer Signifikanz bei Patienten mit Kälteurtikaria und symptomatischem Dermografismus, die nicht auf Antihistaminika ansprachen. Die Studie zeigte signifikante Verbesserungen in den Dosierungsgruppen von 150 mg und 300 mg im Vergleich zu Placebo, wobei bis zu 53,1 % der Patienten mit Kälteurtikaria und 57,6 % der Patienten mit symptomatischem Dermografismus eine vollständige Antwort erzielten. Das Medikament zeigte ein günstiges Sicherheitsprofil, bei dem die meisten unerwünschten Ereignisse Grad 1 waren. Das Unternehmen plant, 2025 in die Phase-3-Entwicklung überzugehen.
- Met all primary and secondary endpoints with high statistical significance
- Up to 53.1% complete response rate in cold urticaria patients
- Up to 57.6% complete response rate in symptomatic dermographism patients
- 90% patient retention rate through 12 weeks
- Rapid disease improvement observed as early as two weeks
- Favorable safety profile with mostly Grade 1 (mild) adverse events
- 13% of patients experienced hair color changes as side effect
- 10% of patients experienced neutropenia as side effect
Insights
The Phase 2 trial results for barzolvolimab represent a significant breakthrough in chronic inducible urticaria treatment. The drug achieved highly statistically significant results across all primary and secondary endpoints, with impressive response rates of
The data demonstrates rapid onset of action within two weeks and strong safety profile, with mostly Grade 1 adverse events. The
This positive Phase 2 data significantly strengthens Celldex's market position in the urticaria space. With plans to advance to Phase 3 in 2025, barzolvolimab could become the first approved targeted therapy for CIndU, potentially capturing a substantial portion of the antihistamine-refractory patient population. The drug's unique mechanism targeting KIT receptor and impressive efficacy data could support premium pricing upon approval.
The strong safety profile and high completion rates suggest potential for broad adoption. For CLDX investors, this represents a major de-risking event for one of the company's lead programs, likely to positively impact market valuation and potentially attract partnership interest from larger pharmaceutical companies.
- First to demonstrate clinical benefit in patients with chronic inducible urticaria (CIndU) in large, randomized, placebo-controlled study
- Favorable safety and tolerability
- Plan to advance CIndU into Phase 3 development
- Company to host webcast call Monday at 8:00 am ET
HAMPTON, N.J., Oct. 26, 2024 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc. (NASDAQ:CLDX) announced today positive results from the Company’s Phase 2 clinical trial of barzolvolimab in two of the most common forms of chronic inducible urticaria (CIndU)—cold urticaria (ColdU) and symptomatic dermographism (SD). The study includes patients who remain symptomatic despite treatment with antihistamines. Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity, which is required for mast cell function and survival. CIndU is characterized by the occurrence of hives or wheals that have an attributable trigger associated with them—exposure to cold temperatures in ColdU and scratching/rubbing of the skin in SD. Mast cell activation is known to be a critical driver in ColdU and SD.
The data were presented in a late breaking oral presentation at the American College of Allergy, Asthma & Immunology's Annual Scientific Meeting in Boston by Dr. Jonathan Bernstein, Professor of Clinical Medicine, Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, University of Cincinnati Medical Center and Partner, Bernstein Allergy Group and Clinical Research Center.
“Chronic inducible urticaria is a devastating disease for patients who despite constant vigilance often find it impossible to avoid their disease triggers and are impacted by severe itching and burning hives that dramatically impact all aspects of their lives,” said Diane C. Young, MD, Senior Vice President and Chief Medical Officer of Celldex Therapeutics. “Barzolvolimab is the first drug to achieve success in a large, randomized, placebo-controlled study in chronic inducible urticaria and we are excited to report that all primary and secondary endpoints across the study were highly statistically significant and clinically meaningful. We believe these study results achieve the goal of treatment for patients by dramatically improving their trigger thresholds and enabling them to regain control of their lives. We are actively working towards bringing this potential new medicine to patients and look forward to initiating Phase 3 development in inducible urticaria in 2025.”
Celldex previously reported that barzolvolimab achieved the primary efficacy endpoint of the study, a statistically significant difference between the percent of patients with a negative provocation test compared to placebo at Week 12 as assessed by the TempTest® in ColdU and the FricTest® in SD. Today the Company reported that all secondary endpoints in the study were also achieved at Week 12 and strongly support the primary endpoint results, including responder analyses, improvements in Critical Temperature and Critical Friction Thresholds (CFT and CFT), changes in WI-NRSprovo (itch associated with provocation test) and Urticaria Control Test.
196 patients with CIndU refractory to antihistamines were randomized to the study and 193 patients were included in the full analysis (mITT) and safety set (3 patients randomized to the study were not treated).
| Summary of Clinical Assessments at Week 12 | |||||||
| Cold Urticaria | Symptomatic Dermographism | ||||||
| All measurements at Week 12 | 150 mg q4w (n=32) | 300 mg q8w (n=32) | Placebo (n=32) | 150 mg q4w (n=33) | 300 mg q8w (n=33) | Placebo (n=31) | |
| Primary endpoint: % of patients with negative provocation test (complete response) | p=0.0023 | p=0.0011 | p<0.0001 | p=0.0003 | |||
| % of patients with complete or partial response per provocation test | p=0.0118 | p=0.0006 | p<0.0001 | p=0.0002 | |||
| Improvement in Critical Temperature (CTT) and Critical Friction (CFT) Thresholds | -8.82°C p<0.0001 | -9.61°C p<0.0001 | -0.30°C | -2.46 pins p<0.0001 | -2.27 pins p=0.0002 | -0.82 pins | |
| % of patients with Urticaria Control Test >12 | p=0.0048 | p<0.0001 | p=0.0015 | p<0.0001 | |||
Patients experienced rapid disease improvement as early as two weeks (the first assessment) after receiving the initial dose of barzolvolimab as demonstrated by reductions in critical temperature and friction thresholds resulting in hives and rapid reduction in itch at the time of provocation testing (WI-NRSprovo).
Barzolvolimab was well tolerated with a favorable safety profile consistent with prior studies. Most adverse events were grade 1 (mild). Through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were hair color changes (
For additional information on this trial (NCT05405660), please visit www.clinicaltrials.gov.
TempTest® and FricTest® are registered trademarks of Moxie GmbH.
Webcast and Conference Call
The Company will host a conference call/webcast on Monday, October 28th to discuss the results at 8:00 am ET. To access the webcast, please visit the Investor Relations page of Celldex’s website at https://ir.celldex.com/events-presentations. Parties interested in participating via telephone may register here to receive the dial-in numbers and unique PIN to seamlessly access the call. Otherwise please access the listen-only webcast link. The archived webcast will be available for a limited time on the Company’s website.
About Barzolvolimab
Barzolvolimab is a humanized monoclonal antibody that binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity. KIT is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells. In certain inflammatory diseases, such as chronic urticaria, mast cell activation plays a central role in the onset and progression of the disease. Barzolvolimab is currently being studied in chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), prurigo nodularis (PN) and eosinophilic esophagitis (EOE) with additional indications planned for the future, including atopic dermatitis (AD).
About the Phase 2 CIndU Study: This study is a randomized, double-blind, placebo-controlled, parallel group study evaluating the efficacy and safety profile of two dose regimens of barzolvolimab in patients with CIndU who remain symptomatic despite antihistamine therapy. 196 patients in 2 cohorts (differentiated by CIndU subtype) including 97 patients with ColdU and 99 patients with SD were randomly assigned on a 1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 20-week treatment phase. Patients then enter a follow-up phase for an additional 24 weeks. The study also includes an Open Label Extension that allows patients with symptoms during the follow-up phase (including patients who were on placebo during the 20-week treatment phase) to receive active study drug for an additional 20 weeks. The primary endpoint of the study is the percentage of patients with a negative provocation test at Week 12 (using TempTest® for ColdU and FricTest® for SD). Secondary endpoints include safety and other assessments of clinical activity including CTT (critical temperature threshold), CFT (critical friction threshold) and WI-NRSprovo (worst itch numeric rating scale associated with provocation testing).
About Chronic Inducible Urticaria (CIndU)
CIndU is characterized by the occurrence of hives or wheals that have an attributable trigger associated with them. ColdU symptoms include itching, burning wheals/hives and angioedema when skin is exposed to cold temperatures. SD symptoms include the development of wheals in response to stroking, scratching or rubbing of the skin. Approximately
About Celldex Therapeutics, Inc.
Celldex is a clinical stage biotechnology company leading the science at the intersection of mast cell biology and the development of transformative therapeutics for patients. Our pipeline includes antibody-based therapeutics which have the ability to engage the human immune system and/or directly affect critical pathways to improve the lives of patients with severe inflammatory, allergic, autoimmune and other devastating diseases. Visit www.celldex.com.
Forward Looking Statement
This release contains "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements are typically preceded by words such as "believes," "expects," "anticipates," "intends," "will," "may," "should," or similar expressions. These forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct or that those goals will be achieved, and you should be aware that actual results could differ materially from those contained in the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to, our ability to successfully complete research and further development and commercialization of Company drug candidates, including barzolvolimab (also referred to as CDX-0159), in current or future indications; the uncertainties inherent in clinical testing and accruing patients for clinical trials; our limited experience in bringing programs through Phase 3 clinical trials; our ability to manage and successfully complete multiple clinical trials and the research and development efforts for our multiple products at varying stages of development; the availability, cost, delivery and quality of clinical materials produced by our own manufacturing facility or supplied by contract manufacturers, who may be our sole source of supply; the timing, cost and uncertainty of obtaining regulatory approvals; the failure of the market for the Company's programs to continue to develop; our ability to protect the Company's intellectual property; the loss of any executive officers or key personnel or consultants; competition; changes in the regulatory landscape or the imposition of regulations that affect the Company's products; our ability to continue to obtain capital to meet our long-term liquidity needs on acceptable terms, or at all, including the additional capital which will be necessary to complete the clinical trials that we have initiated or plan to initiate; and other factors listed under "Risk Factors" in our annual report on Form 10-K and quarterly reports on Form 10-Q.
All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this release. We have no obligation, and expressly disclaim any obligation, to update, revise or correct any of the forward-looking statements, whether as a result of new information, future events or otherwise.
Company Contact
Sarah Cavanaugh
Senior Vice President, Corporate Affairs & Administration
(508) 864-8337
scavanaugh@celldex.com
Patrick Till
Meru Advisors
(484) 788-8560
ptill@meruadvisors.com
FAQ
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