Protagonist Reports Positive Top Line Results From Phase 2b Study of Icotrokinra Showing Potential to Transform the Treatment Paradigm for Patients With Ulcerative Colitis
Protagonist Therapeutics (PTGX) has announced positive topline results from ANTHEM-UC, a Phase 2b study of icotrokinra (JNJ-2113), the first targeted oral peptide selectively blocking the IL-23 receptor, in adults with moderately to severely active ulcerative colitis.
The study, conducted with Johnson & Johnson, met its primary endpoint of clinical response across all dose groups. The highest dose achieved a 63.5% response rate at Week 12 (vs 27.0% placebo) and a 30.2% clinical remission rate (vs 11.1% placebo), with both results being statistically significant (p<0.001). Clinical remission and response rates continued improving through Week 28.
Icotrokinra demonstrated favorable safety, with adverse events comparable between treatment and placebo groups. The drug's potential as a once-daily oral treatment could transform the UC treatment landscape, with plans for advancement into more advanced clinical studies for both ulcerative colitis and Crohn's disease.
Protagonist Therapeutics (PTGX) ha annunciato risultati positivi preliminari dallo studio ANTHEM-UC, uno studio di Fase 2b su icotrokinra (JNJ-2113), il primo peptide orale mirato che blocca selettivamente il recettore dell'IL-23, in adulti con colite ulcerosa attiva da moderata a severa.
Lo studio, condotto in collaborazione con Johnson & Johnson, ha raggiunto il suo obiettivo primario di risposta clinica in tutti i gruppi di dosaggio. La dose più alta ha ottenuto un 63.5% di tasso di risposta alla Settimana 12 (rispetto al 27.0% del placebo) e un 30.2% di tasso di remissione clinica (rispetto all'11.1% del placebo), con entrambi i risultati statisticamente significativi (p<0.001). I tassi di remissione e risposta clinica hanno continuato a migliorare fino alla Settimana 28.
Icotrokinra ha dimostrato un profilo di sicurezza favorevole, con eventi avversi comparabili tra i gruppi di trattamento e placebo. Il potenziale del farmaco come trattamento orale una volta al giorno potrebbe trasformare il panorama terapeutico della colite ulcerosa, con piani per avanzare verso studi clinici più avanzati sia per la colite ulcerosa che per la malattia di Crohn.
Protagonist Therapeutics (PTGX) ha anunciado resultados preliminares positivos del estudio ANTHEM-UC, un estudio de Fase 2b sobre icotrokinra (JNJ-2113), el primer péptido oral dirigido que bloquea selectivamente el receptor de IL-23, en adultos con colitis ulcerosa activa de moderada a severa.
El estudio, realizado en colaboración con Johnson & Johnson, alcanzó su objetivo primario de respuesta clínica en todos los grupos de dosis. La dosis más alta logró una tasa de respuesta del 63.5% a la Semana 12 (frente al 27.0% del placebo) y una tasa de remisión clínica del 30.2% (frente al 11.1% del placebo), siendo ambos resultados estadísticamente significativos (p<0.001). Las tasas de remisión y respuesta clínica continuaron mejorando hasta la Semana 28.
Icotrokinra demostró un perfil de seguridad favorable, con eventos adversos comparables entre los grupos de tratamiento y placebo. El potencial del fármaco como tratamiento oral una vez al día podría transformar el panorama del tratamiento de la colitis ulcerosa, con planes para avanzar a estudios clínicos más avanzados tanto para la colitis ulcerosa como para la enfermedad de Crohn.
Protagonist Therapeutics (PTGX)는 중등도에서 중증의 활성 궤양성 대장염 성인을 대상으로 한 icotrokinra (JNJ-2113)의 2b상 ANTHEM-UC 연구에서 긍정적인 최종 결과를 발표했습니다. 이 약물은 IL-23 수용체를 선택적으로 차단하는 최초의 표적 경구 펩타이드입니다.
Johnson & Johnson과 함께 진행된 이 연구는 모든 용량 그룹에서 임상 반응의 주요 목표를 달성했습니다. 가장 높은 용량은 12주 차에 63.5%의 반응률(위약의 27.0% 대비)을 기록했으며, 30.2%의 임상 관해율(위약의 11.1% 대비)을 달성했으며, 두 결과 모두 통계적으로 유의미했습니다 (p<0.001). 임상 관해 및 반응률은 28주 차까지 계속 개선되었습니다.
Icotrokinra는 치료 그룹과 위약 그룹 간의 불리한 사건이 유사하여 안전성이 우수함을 보여주었습니다. 하루 한 번 복용할 수 있는 이 약물의 잠재력은 궤양성 대장염 치료 환경을 변화시킬 수 있으며, 궤양성 대장염과 크론병 모두에 대한 보다 고급 임상 연구로의 발전 계획이 있습니다.
Protagonist Therapeutics (PTGX) a annoncé des résultats préliminaires positifs de l'étude ANTHEM-UC, une étude de Phase 2b sur icotrokinra (JNJ-2113), le premier peptide oral ciblé bloquant sélectivement le récepteur IL-23, chez des adultes atteints de colite ulcéreuse active modérée à sévère.
L'étude, réalisée en collaboration avec Johnson & Johnson, a atteint son objectif principal de réponse clinique dans tous les groupes de dose. La dose la plus élevée a obtenu un taux de réponse de 63,5% à la Semaine 12 (contre 27,0% pour le placebo) et un taux de rémission clinique de 30,2% (contre 11,1% pour le placebo), les deux résultats étant statistiquement significatifs (p<0,001). Les taux de rémission et de réponse clinique ont continué à s'améliorer jusqu'à la Semaine 28.
Icotrokinra a démontré un profil de sécurité favorable, avec des événements indésirables comparables entre les groupes de traitement et de placebo. Le potentiel du médicament en tant que traitement oral quotidien pourrait transformer le paysage thérapeutique de la colite ulcéreuse, avec des plans pour avancer vers des études cliniques plus avancées tant pour la colite ulcéreuse que pour la maladie de Crohn.
Protagonist Therapeutics (PTGX) hat positive vorläufige Ergebnisse aus der ANTHEM-UC-Studie, einer Phase-2b-Studie zu icotrokinra (JNJ-2113), dem ersten gezielten oralen Peptid, das den IL-23-Rezeptor selektiv blockiert, bei Erwachsenen mit moderat bis schwer aktiver Colitis ulcerosa bekannt gegeben.
Die Studie, die in Zusammenarbeit mit Johnson & Johnson durchgeführt wurde, erreichte ihr primäres Ziel der klinischen Reaktion in allen Dosisgruppen. Die höchste Dosis erzielte eine 63,5%ige Ansprechrate nach 12 Wochen (im Vergleich zu 27,0% bei Placebo) und eine 30,2%ige Remissionsrate (im Vergleich zu 11,1% bei Placebo), wobei beide Ergebnisse statistisch signifikant waren (p<0,001). Die Raten für klinische Remission und Reaktion verbesserten sich bis zur Woche 28 weiter.
Icotrokinra zeigte ein günstiges Sicherheitsprofil, mit vergleichbaren unerwünschten Ereignissen zwischen Behandlungs- und Placebogruppen. Das Potenzial des Medikaments als einmal täglich einzunehmende orale Therapie könnte die Behandlung von Colitis ulcerosa revolutionieren, mit Plänen für den Fortschritt zu fortgeschritteneren klinischen Studien sowohl für Colitis ulcerosa als auch für Morbus Crohn.
- All doses met primary endpoint with statistically significant clinical response
- High efficacy: 63.5% response rate and 30.2% remission rate at highest dose
- Continued improvement in clinical outcomes through Week 28
- Favorable safety profile comparable to placebo
- Potential expansion into Crohn's disease indication
- Phase 2b results still require confirmation in larger Phase 3 trials
- Further studies needed before potential market approval
Insights
Protagonist's Phase 2b ANTHEM-UC trial results for icotrokinra represent a significant advancement in ulcerative colitis treatment. The data shows remarkably strong efficacy with the highest dose achieving
What's particularly notable is that this oral peptide selectively blocks the IL-23 receptor, offering a first-in-class mechanism that could disrupt the inflammatory bowel disease market currently dominated by injectable biologics. The continued improvement through Week 28 suggests durable efficacy beyond the primary endpoint timeframe, addressing a critical need for sustained response in chronic UC management.
The favorable safety profile, with adverse events comparable to placebo, creates a compelling risk-benefit proposition that could position icotrokinra as a preferred option for both clinicians and patients. With Johnson & Johnson as their development partner, Protagonist benefits from substantial clinical development expertise and commercial infrastructure to advance this potential breakthrough therapy.
This success builds upon their positive Phase 3 psoriasis data, demonstrating icotrokinra's versatility across multiple inflammatory conditions and validating Protagonist's oral peptide platform technology. The expansion into inflammatory bowel diseases significantly broadens the addressable market opportunity and enhances the drug's commercial potential.
The ANTHEM-UC study results for icotrokinra represent a potentially transformative development for ulcerative colitis management. As an oral IL-23 receptor antagonist, this drug introduces a novel therapeutic approach in a disease where injectable biologics and systemic immunosuppressants currently dominate advanced care.
The
From a clinical perspective, the continued improvement through Week 28 addresses a critical therapeutic need, as maintenance of remission represents a significant challenge in UC management. The clean safety profile is equally important given that many current treatments carry risks of serious infections, malignancies, or other complications.
The success of this targeted oral peptide technology could significantly impact treatment algorithms and patient care. Current step therapy typically progresses from mesalamine to immunomodulators and then to biologics, with each step introducing greater inconvenience and potential side effects. An efficacious, safe oral option could potentially be positioned earlier in treatment protocols, allowing patients to avoid or delay progression to injectable therapies while effectively controlling their disease.
Clinical response rate of
All three doses met the primary endpoint of clinical response at Week 12, with a favorable safety profile
These results in ulcerative colitis build on strong data recently reported for the plaque psoriasis Phase 3 program
NEWARK, CALIFORNIA / ACCESS Newswire / March 10, 2025 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") today announced positive topline results from ANTHEM-UC, a Phase 2b study of icotrokinra (JNJ-2113), the first investigational targeted oral peptide that selectively blocks the IL-23 receptor, in adults with moderately to severely active ulcerative colitis (UC). The study conducted by Protagonist's collaboration partner, Johnson & Johnson, met its primary endpoint of clinical responsea in all icotrokinra dose groups evaluated. Additionally, the study demonstrated clinically meaningful differences versus placebo in key secondary endpoints of clinical remissionb, symptomatic remission and endoscopic improvement at Week 12.
Key findings from the ANTHEM-UC study (n=252) are summarized below:
All three doses of once daily icotrokinra met the primary endpoint of clinical response at Week 12.
A response rate of
63.5% for patients treated with the highest dose of icotrokinra was achieved at Week 12 versus27.0% for placebo (p<0.001).30.2% of patients treated with the highest dose of icotrokinra demonstrated clinical remission at Week 12 versus11.1% of patients who received placebo (p<0.001).Clinical remission and response rates continued to improve through Week 28.i
Icotrokinra was well tolerated with the proportions of participants reporting one or more adverse events (AEs) being similar between the icotrokinra dose groups and the placebo group.i
"We are thrilled with the impressive results of once daily oral icotrokinra in the ANTHEM Phase 2 ulcerative colitis study, broadening the potential utility of this first-in-class and only-in-class oral IL-23 receptor antagonist from psoriasis to inflammatory bowel diseases," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. "This is another example of Protagonist's oral peptide platform delivering transformative, paradigm shifting outcomes in the hands of a world-leading development partner. Icotrokinra has the potential to transform the treatment landscape in UC through its distinctive profile of efficacy, safety, tolerability, and convenience of a once-daily oral treatment. We eagerly await icotrokinra's further progression into more advanced clinical studies in ulcerative colitis and Crohn's disease."
Comprehensive results from the ANTHEM-UC study are being prepared for presentation at upcoming medical congresses by our partner.
Editor's notes:
Clinical response is defined as decrease from baseline in the modified Mayo score by greater than or equal to (>=) 30 percent (%) and >=2 points, with either a >=1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.
Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1 and not increased from induction baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy.
About ANTHEM-UC
ANTHEM-UC (NCT06049017) is a Phase 2b multicenter, randomized, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of icotrokinra (JNJ-77242113, JNJ-2113) in patients with moderately to severely active ulcerative colitis who had an inadequate response or intolerance to conventional therapy (e.g., thiopurines or corticosteroids), prior biologics (TNF antagonists or vedolizumab) and/or ozanimod or approved JAK inhibitors. The study is evaluating three once-daily dosages of icotrokinra taken orally.ii
About Ulcerative Colitis
Ulcerative colitis (UC) is a chronic disease of the large intestine, also known as the colon, in which the lining of the colon becomes inflamed and develops tiny open sores, or ulcers, that produce pus and mucus. It is the result of the immune system's overactive response.Symptoms vary but may typically include loose and more urgent bowel movements, rectal bleeding or bloody stool, persistent diarrhea, abdominal pain, loss of appetite, weight loss, and fatigue.iii
About Icotrokinra (JNJ-77242113, JNJ-2113)
Investigational icotrokinra is the first targeted oral peptide designed to selectively block the IL-23 receptor,iv which underpins the inflammatory response in moderate-to-severe plaque psoriasis, ulcerative colitis and offers potential in other IL-23-mediated diseases.v,vi Icotrokinra binds to the IL-23 receptor with single-digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signaling in human T cells.vii The license and collaboration agreement established between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc., a Johnson & Johnson company, in 2017 enabled the companies to work together to discover and develop next-generation compounds that ultimately led to icotrokinra.viii Icotrokinra was jointly discovered and is being developed pursuant to the license and collaboration agreement between Protagonist and Johnson & Johnson. Johnson & Johnson retains exclusive worldwide rights to develop icotrokinra in Phase 2 clinical trials and beyond, and to commercialize compounds derived from the research conducted pursuant to the agreement against a broad range of indications.ix,x,xi
Icotrokinra is being studied in the pivotal Phase 3 ICONIC clinical development program in moderate-to-severe plaque psoriasis and active psoriatic arthritis and the Phase 2b ANTHEM-UC study in moderately to severely active ulcerative colitis.
About Protagonist
Protagonist Therapeutics is a discovery through late-stage development biopharmaceutical company. Two novel peptides, icotrokinra and rusfertide, derived from Protagonist's proprietary discovery platform are currently in advanced Phase 3 clinical development, with New Drug Application submissions to the FDA expected in 2025. Icotrokinra (JNJ-2113) is a first-in-class investigational targeted oral peptide that selectively blocks the Interleukin-23 receptor ("IL-23R") which is licensed to Janssen Biotech, Inc., a Johnson & Johnson company. Following icotrokinra's joint discovery by Protagonist and Johnson & Johnson scientists pursuant to the companies' IL-23R collaboration, Protagonist was primarily responsible for development of icotrokinra through Phase 1, with Johnson & Johnson assuming responsibility for development in Phase 2 and beyond. Rusfertide, a mimetic of the natural hormone hepcidin, is currently in Phase 3 development for the rare blood disorder polycythemia vera (PV). Rusfertide is being co-developed and will be co-commercialized with Takeda Pharmaceuticals pursuant to a worldwide collaboration and license agreement entered into in 2024 under which the Company remains primarily responsible for development through NDA filing. The Company also has a number of pre-clinical stage oral drug discovery programs addressing clinically and commercially validated targets, including the IL-17 oral peptide antagonist PN-881, an oral hepcidin program, and an oral obesity program.
More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at www.protagonist-inc.com .
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the potential benefits of icotrokinra, and expectations regarding the icotrokinra development program. In some cases, you can identify these statements by forward-looking words such as "anticipate," "believe," "may," "will," "expect," or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, our ability to earn milestone payments under our collaboration agreements with Janssen and Takeda, our ability to use and expand our programs to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, and our ability to obtain and adequately protect intellectual property rights for our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the Securities and Exchange Commission, including under the heading "Risk Factors" contained in our most recently filed periodic reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release.
Investor Relations Contact
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LifeSci Advisors
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i Data on file.
ii Clinicaltrials.gov. A Study of JNJ-77242113 in Participants With Moderately to Severely Active Ulcerative Colitis (ANTHEM-UC). Identifier NCT06049017. https://clinicaltrials.gov/study/NCT06049017?term=ANTHEM-UC&rank=1. Accessed March 2025.
iii Crohn's & Colitis Foundation. What is ulcerative colitis? Available at: https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis. Accessed March 2025.
iv Bissonnette R, et al. Data presentation. A phase 2, randomized, placebo-controlled, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis: FRONTIER 1. Presented at WCD 2023, July 3-8.
v Razawy W, et al. The role of IL‐23 receptor signaling in inflammation‐mediated erosive autoimmune arthritis and bone remodeling. Eur J Immunol. 2018 Feb; 48(2): 220-229.
vi Tang C, et al. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology. 2012 Feb; 135(2): 112-124.
vii Pinter A, et al. Data Presentation. JNJ-77242113 Treatment Induces a Strong Systemic Pharmacodynamic Response Versus Placebo in Serum Samples of Patients with Plaque Psoriasis: Results from the Phase 2, FRONTIER 1 Study. Presented at EADV 2023, October 11-14.
viii Johnson & Johnson. Press release. Janssen enters into worldwide exclusive license and collaboration agreement with Protagonist Therapeutics, Inc. for the oral Interlukin-23 receptor antagonist drug candidate for the treatment of Inflammatory Bowel Disease. Available at: https://www.jnj.com/media-center/press-releases/janssen-enters-into-worldwide-exclusive-license-and-collaboration-agreement-with-protagonist-therapeutics-inc-for-the-oral-interlukin-23-receptor-antagonist-drug-candidate-for-the-treatment-of-inflammatory-bowel-disease. Accessed March 2025.
ixProtagonist Therapeutics. Press release. Protagonist Therapeutics announces amendment of agreement with Janssen Biotech for the continued development and commercialization of IL-23 antagonists. Available at: https://feeds.issuerdirect.com/news-release.html?newsid=8739644264127846. Accessed March 2025.
x Protagonist Therapeutics. Press release. Protagonist Reports positive results from Phase 1 and pre-clinical studies of oral Interleukin-23 receptor antagonist JNJ-2113. Available at: https://feeds.issuerdirect.com/news-release.html?newsid=8812150281946506. Accessed March 2025.
xi Protagonist Therapeutics. Press release. Protagonist Therapeutics announces positive topline results for Phase 2b FRONTIER 1 clinical trial of oral IL-23 receptor antagonist JNJ-2113 (PN-235) in psoriasis. Available at: https://feeds.issuerdirect.com/news-release.html?newsid=6598557738756234. Accessed March 2025.
SOURCE: Protagonist Therapeutics
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FAQ
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