Nipocalimab demonstrates significant clinical improvement in disease activity and IgG reduction in Phase 2 Sjögren's disease study
Johnson & Johnson (NYSE: JNJ) announced positive results from the Phase 2 DAHLIAS study of nipocalimab in treating moderate-to-severe Sjögren's disease. The investigational FcRn blocker demonstrated significant clinical improvements, with patients showing over 77% reduction in IgG levels and meeting primary endpoints in ClinESSDAI scores at 24 weeks. Key secondary endpoints were also met, showing reduced disease activity across multiple organ systems. The treatment showed particular effectiveness in patients with high baseline anti-Ro and anti-La autoantibodies. Notably, more than twice as many patients in the high-dose group (15 mg/kg) showed improved salivary flow compared to placebo (32.7% vs. 16%) at Week 24.
Johnson & Johnson (NYSE: JNJ) ha annunciato risultati positivi dallo studio di Fase 2 DAHLIAS riguardo al nipocalimab nel trattamento della sindrome di Sjögren da moderata a severa. Il bloccante FcRn in fase di sperimentazione ha mostrato miglioramenti clinici significativi, con i pazienti che hanno evidenziato una riduzione superiore al 77% dei livelli di IgG e che hanno raggiunto gli obiettivi primari nei punteggi ClinESSDAI a 24 settimane. Sono stati raggiunti anche obiettivi secondari chiave, mostrando una riduzione dell'attività della malattia in diversi sistemi organici. Il trattamento ha mostrato particolare efficacia nei pazienti con livelli elevati di autoanticorpi anti-Ro e anti-La. È interessante notare che oltre il doppio dei pazienti nel gruppo ad alta dose (15 mg/kg) ha mostrato un flusso salivare migliorato rispetto al placebo (32,7% contro 16%) alla settimana 24.
Johnson & Johnson (NYSE: JNJ) anunció resultados positivos del estudio de Fase 2 DAHLIAS sobre nipocalimab en el tratamiento de la enfermedad de Sjögren de moderada a severa. El bloqueador FcRn en investigación mostró mejoras clínicas significativas, con pacientes que mostraron más del 77% de reducción en los niveles de IgG y alcanzando los objetivos primarios en las puntuaciones de ClinESSDAI a las 24 semanas. También se cumplieron los objetivos secundarios clave, mostrando una disminución de la actividad de la enfermedad en múltiples sistemas orgánicos. El tratamiento mostró una efectividad particular en pacientes con altos niveles basales de autoanticuerpos anti-Ro y anti-La. Notablemente, más del doble de pacientes en el grupo de dosis alta (15 mg/kg) mostraron un flujo salival mejorado en comparación con el placebo (32.7% frente a 16%) a la semana 24.
Johnson & Johnson (NYSE: JNJ)는 중등도에서 중증의 쇼그렌 증후군 치료를 위한 nipocalimab의 2상 DAHLIAS 연구에서 긍정적인 결과를 발표했습니다. 연구 대상 FcRn 차단제는 의미 있는 임상 개선을 보여주었으며, 환자들은 IgG 수치에서 77% 이상의 감소를 보였고 24주차까지 ClinESSDAI 점수의 주요 목표를 달성했습니다. 핵심 이차 목표 또한 달성되어 여러 장기 시스템에서 질병 활동성이 감소했습니다. 이 치료는 기초에서 높은 수준의 항-Ro 및 항-La 자가항체를 가진 환자에게 특히 효과적이었습니다. 특히, 고용량 그룹(15 mg/kg)에서 치료를 받은 환자는 위약 그룹에 비해 개선된 타액 분비를 보인 비율이 두 배 이상이었습니다(32.7% 대 16%) 24주째에.
Johnson & Johnson (NYSE: JNJ) a annoncé des résultats positifs de l'étude de Phase 2 DAHLIAS sur le nipocalimab dans le traitement de la maladie de Sjögren modérée à sévère. Le bloqueur FcRn expérimental a démontré des améliorations cliniques significatives, avec des patients montrant une réduction de plus de 77 % des niveaux d'IgG et atteignant les objectifs primaires dans les scores ClinESSDAI à 24 semaines. Les objectifs secondaires clés ont également été atteints, montrant une réduction de l'activité de la maladie dans plusieurs systèmes organiques. Le traitement s'est montré particulièrement efficace chez les patients avec des auto-anticorps anti-Ro et anti-La élevés à la base. Notamment, plus du double des patients dans le groupe à forte dose (15 mg/kg) ont montré un flux salivaire amélioré par rapport au groupe placebo (32,7 % contre 16 %) à la semaine 24.
Johnson & Johnson (NYSE: JNJ) gab positive Ergebnisse aus der Phase-2-Studie DAHLIAS über nipocalimab zur Behandlung der moderaten bis schweren Sjögren-Krankheit bekannt. Der experimentelle FcRn-Blocker zeigte signifikante klinische Verbesserungen, wobei die Patienten eine Reduktion der IgG-Spiegel um über 77% zeigten und die primären Endpunkte in den ClinESSDAI-Werten nach 24 Wochen erreichten. Wichtige sekundäre Endpunkte wurden ebenfalls erreicht, die eine verminderte Krankheitsaktivität in mehreren Organsystemen zeigten. Die Behandlung erwies sich als besonders effektiv bei Patienten mit hohen Ausgangswerten an Anti-Ro- und Anti-La-Autoantikörpern. Bemerkenswerterweise zeigte mehr als doppelt so viele Patienten in der Hochdosisgruppe (15 mg/kg) im Vergleich zur Placebo-Gruppe einen verbesserten Speichelfluss (32,7% gegenüber 16%) nach 24 Wochen.
- Achieved primary endpoint with significant improvement in ClinESSDAI score at 24 weeks
- Demonstrated over 77% reduction in IgG levels
- 32.7% of high-dose patients showed improved salivary flow vs 16% in placebo group
- Received FDA Breakthrough Therapy Designation
- Met key secondary endpoints for reduced disease activity
- None.
Insights
The Phase 2 DAHLIAS study results for nipocalimab represent a significant breakthrough in Sjögren's disease treatment. The data shows impressive efficacy with a
The FDA's Breakthrough Therapy Designation underscores the potential impact of this treatment in a disease area with no currently approved advanced therapies. The drug's mechanism targeting FcRn, combined with its effect on multiple organ systems and autoantibody reduction, suggests a comprehensive approach to treating both glandular and extraglandular manifestations of Sjögren's disease.
This development strengthens JNJ's position in the autoimmune disease market, particularly important as the company seeks to expand its immunology portfolio. With no advanced therapies currently approved for Sjögren's disease, nipocalimab could capture a significant market share in this underserved indication. The global Sjögren's syndrome therapeutic market is projected to grow substantially, representing a valuable commercial opportunity for JNJ.
The Breakthrough Therapy Designation will accelerate the regulatory pathway, potentially leading to earlier market entry and extended market exclusivity. This could translate into meaningful revenue growth for JNJ's pharmaceutical division, especially given the chronic nature of the disease requiring long-term treatment.
Adults with moderately-to-severely active Sjögren's disease who received investigational FcRn blocker nipocalimab had improvements in disease activity scores at 24 weeks with accompanying significant reductions in IgG and autoantibody levels
Nipocalimab was granted
Patients receiving nipocalimab, an investigational FcRn blocker, showed a significant improvement in the ClinESSDAIa score at 24 weeks, achieving the primary endpoint. Additionally, key secondary endpoints were met, indicating reduced disease activity both systemically and across multiple organ systems, as well as improvements in physician assessments and composite SjD assessment tools.
Results also showed a significant reduction in IgG including autoantibody levels among patients receiving 15 mg/kg every two weeks, providing further evidence of nipocalimab's mechanism of action through interaction with the FcRn. Moreover, improvements in ClinESSDAI were generally greatest in the participants with the highest baseline levels of anti-Ro and anti-La autoantibodies, associated with substantial nipocalimab-induced reductions in IgG and total IgG autoantibodies.
"These data highlight the relevance of autoantibodies in SjD pathogenesis. The observed reduction in IgG and pivotal autoantibodies, particularly the anti-Ro antibodies, in association with improvement in systemic disease activity and saliva production, represent an exciting advance in our understanding of the disease and how it may be treated effectively. I am also encouraged by the observed trend in many patient-reported measures as they are most important to patients. I look forward to future research to confirm these observations," said Ghaith Noaiseh, M.D., Associate Professor, Allergy, Clinical Immunology, and Rheumatology, The University of Kansas Medical Center.b "People living with SjD need targeted treatment options that can help address the underlying causes and alleviate the potentially serious health consequences of the disease."
Many people living with SjD experience symptoms that interfere with daily activities and quality of life, including chronic and severe mucosal dryness.1,2 Extraglandular manifestations – more systemic symptoms of SjD – are also common and may impact multiple organ systems, including joints, lungs, kidneys, and nervous system.3 These patients with high activity in more than one organ or disease area have an increased mortality risk of up to five-fold.4
In the Phase 2 study, patients reported a decrease in symptoms, with numerical improvements compared with placebo in the symptom categories most important to them, including mouth dryness, eye dryness, vaginal dryness, fatigue and joint pain. Additionally, an improvement in objective salivary flow (i.e., at least
"No advanced therapies have been approved for SjD to date. A clear need exists for new immunoselective treatments with demonstrated safety profiles that can provide sustained relief from the heavy burden of the overall disease for patients living with SjD," said Federico Zazzetti, Director, Rheumatology, Global Medical Affairs Lead, Johnson & Johnson Innovative Medicine. "Johnson & Johnson is committed to continued research to help address this unmet need, and the data presented at ACR demonstrate the potential of nipocalimab in a disease where patients have very few options."
Editor's Notes:
A. | ClinESSDAI is an endpoint specific to SjD and is a composite scale that assesses organ disease activity across 11 organ system domains [cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system (PNS), central nervous system (CNS), hematological, glandular, constitutional, lymphadenopathy and lymphoma]; a higher score indicates greater symptom severity. |
B. | Ghaith Noaiseh, M.D., Ph.D. is a paid consultant for Johnson & Johnson. He has not been compensated for any media work. |
ABOUT SJÖGREN'S DISEASE
Sjögren's disease (SjD) is one of the most prevalent autoantibody-driven diseases for which no therapies are currently approved that treat the underlying and systemic nature of the disease.4 It is a chronic autoimmune disease that is estimated to impact approximately four million people worldwide and is nine times more common in women than men.5,6 SjD is characterized by autoantibody production, chronic inflammation, and lymphocytic infiltration of exocrine glands. Most patients are affected by mucosal dryness (eyes, mouth, vagina), joint pain and fatigue.4 More than
ABOUT DAHLIAS
DAHLIAS (NCT04969812) is a Phase 2 multicenter, randomized, placebo-controlled double-blind study to evaluate the effects of nipocalimab in participants with primary SjD. DAHLIAS is a Phase 2 dose-ranging study of adults with moderately-to-severely active primary SjD who were seropositive for anti-Ro60 and/or anti-Ro52 IgG antibodies. 163 adults aged 18-75 were randomized 1:1:1 to receive intravenous nipocalimab at 5 or 15 mg/kg or placebo every two weeks through Week 22 and received protocol-permitted background standard of care. Safety assessments were conducted through Week 30. The primary endpoint was change in baseline in the ClinESSDAI Score at Week 24. Select secondary endpoints included:
- Multiple organ system assessments:
- European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) is a systemic diseases activity index designed to measure disease activity in patients with primary SjD. It is based on 12 domains including: constitutional, lymphadenopathy, glandular, articular, cutaneous, respiratory, renal, muscular, peripheral nervous system, central nervous system, biological, and hematological.
- Disease Activity Level (DAL) response is a reduction from baseline in disease activity level by at least one level in at least one ClinESSDAI domain (e.g., articular, hematological, cutaneous, constitutional).
- Physician assessment:
- The Physician Global Assessment of Disease Severity (PhGA) is recorded by the investigator, independent of study participants' assessment, on a scale with responses ranging from 0 ("No SjD activity") to 100 ("Extremely active SjD").
- Composite tools for clinical trial endpoints:
- Sjögren's Tool for Assessing Response (STAR) is a composite responder index that includes all main SjD features, including systemic disease activity, patient-reported symptoms, tear gland item, salivary gland item and serology, in a single tool.
- Composite of Relevant Endpoints for Sjogren's Syndrome (CRESS), a composite endpoint tool consisting of five complementary items: systemic disease activity, patient-reported symptoms, tear gland item, salivary gland item and serology, for use in trials of primary SjD.
- Patient reported outcomes:
- European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) is a patient-reported assessment of the severity of dryness, fatigue, and pain associated with primary SjD, in which patients report their symptom severity over the last two weeks on a numeric rating scale (NRS), ranging from 0 "No symptoms (dryness, fatigue or pain)" to 10 "maximal imaginable (dryness, fatigue, pain)".
- Sjögren's Symptoms tool is a patient-reported assessment of the worst severity of their ocular, oral, and vaginal dryness and joint pain over the past 7 days on a 0 to 10 NRS, from 0 "No [specific symptom]" to 10, "Severe [specific symptom]".
ABOUT NIPOCALIMAB
Nipocalimab is an investigational monoclonal antibody, designed to bind with high affinity to block FcRn and reduce levels of circulating immunoglobulin G (IgG) antibodies potentially without impact on other immune functions. This includes autoantibodies and alloantibodies that underlie multiple conditions across three key segments in the autoantibody space including Rare Autoantibody diseases, Maternal Fetal diseases mediated by maternal alloantibodies and Prevalent Rheumatology.8,9,10,11,12,13,14,15,16 Blockade of IgG binding to FcRn in the placenta is also believed to limit transplacental transfer of maternal alloantibodies to the fetus.17,18
The
U.S. FDA Fast Track designation in hemolytic disease of the fetus and newborn (HDFN) and warm autoimmune hemolytic anemia (wAIHA) in July 2019, gMG in December 2021 and fetal neonatal alloimmune thrombocytopenia (FNAIT) in March 2024U.S. FDA Orphan drug status for wAIHA in December 2019, HDFN in June 2020, gMG in February 2021, chronic inflammatory demyelinating polyneuropathy (CIDP) in October 2021 and FNAIT in December 2023U.S. FDA Breakthrough Therapy designation for HDFN in February 2024 and for SjD in November 2024- EU EMA Orphan medicinal product designation for HDFN in October 2019
ABOUT JOHNSON & JOHNSON
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.
Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com.
Follow us at @JanssenUS and @JNJInnovMed.
Janssen Research & Development, LLC, Janssen Biotech, Inc. and Janssen Global Services, LLC are Johnson & Johnson companies.
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of nipocalimab. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
1 Sjogren's Disease Foundation. Understanding Sjogrens – Treatment. Available at: https://sjogrens.org/. Last accessed: November 2024.
2 McCoy SS, Woodham M, Bunya VY, Saldanha IJ, Akpek EK, Makara MA, Baer AN. A comprehensive overview of living with Sjögren's: results of a National Sjögren's Foundation survey. Clin Rheumatol. 2022 Jul;41(7):2071-2078. doi: 10.1007/s10067-022-06119-w. Epub 2022 Mar 8. PMID: 35257256; PMCID: PMC9610846.
3 Carsons SE, Patel BC. Sjogren Syndrome. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431049/
4 Huang H, Xie W, Geng Y, Fan Y, Zhang Z. Mortality in patients with primary Sjögren's syndrome: a systematic review and meta-analysis. Rheumatology (Oxford). 2021 Sep 1;60(9):4029-4038. doi: 10.1093/rheumatology/keab364. PMID: 33878179.
5 Nat Rev Rheumatol 20, 158–169 (2024). https://doi.org/10.1038/s41584-023-01057-6
6 Beydon, M., McCoy, S., Nguyen, Y. et al. Epidemiology of Sjögren syndrome.
7 Hackett KL, et al. Arthritis Care Res (Hoboken). 2012;64(11):1760-1764.
8 ClinicalTrials.gov Identifier: NCT04968912. Available at: https://clinicaltrials.gov/study/NCT04968912. Last accessed: November 2024.
9 ClinicalTrials.gov Identifier: NCT04951622. Available at: https://clinicaltrials.gov/ct2/show/NCT04951622. Last accessed: November 2024.
10 ClinicalTrials.gov Identifier: NCT05327114. Available at: https://www.clinicaltrials.gov/study/NCT05327114. Last accessed: November 2024.
11 ClinicalTrials.gov Identifier: NCT04119050. Available at: https://clinicaltrials.gov/study/NCT04119050. Last accessed: November 2024.
12 ClinicalTrials.gov Identifier: NCT05379634. Available at: https://clinicaltrials.gov/study/NCT05379634. Last accessed: November 2024.
13 ClinicalTrials.gov Identifier: NCT05912517. Available at: https://www.clinicaltrials.gov/study/NCT05912517. Last accessed: November 2024.
14 ClinicalTrials.gov Identifier: NCT06028438. Available at: https://clinicaltrials.gov/study/NCT06028438. Last accessed: November 2024.
15 ClinicalTrials.gov Identifier: NCT04882878. Available at: https://clinicaltrials.gov/study/NCT04882878. Last accessed: November 2024.
16 ClinicalTrials.gov. NCT03842189. Available at: https://clinicaltrials.gov/ct2/show/NCT03842189. Last accessed: November 2024.
17 Lobato G, Soncini CS. Relationship between obstetric history and Rh(D) alloimmunization severity. Arch Gynecol Obstet. 2008 Mar;277(3):245-8. DOI: 10.1007/s00404-007-0446-x. Last accessed: November 2024.
18 Roy S, Nanovskaya T, Patrikeeva S, et al. M281, an anti-FcRn antibody, inhibits IgG transfer in a human ex vivo placental perfusion model. Am J Obstet Gynecol. 2019;220(5):498 e491-498 e499.
Media contact: | Investor contact: |
Bridget Kimmel | Lauren Johnson |
Mobile: (215) 688-6033 | |
View original content to download multimedia:https://www.prnewswire.com/news-releases/nipocalimab-demonstrates-significant-clinical-improvement-in-disease-activity-and-igg-reduction-in-phase-2-sjogrens-disease-study-302305831.html
SOURCE Johnson & Johnson
FAQ
What were the main results of JNJ's Phase 2 DAHLIAS study for nipocalimab?
What percentage of patients showed improved salivary flow in JNJ's nipocalimab study?
Has nipocalimab received any FDA designations for Sjögren's disease treatment?
