New Phase 2b Data Show the Majority of Adults with Moderately to Severely Active Ulcerative Colitis Achieved Clinical Response with TREMFYA®▼ (guselkumab) at 12 Weeks

New Phase 2b Data Show the Majority of Adults with Moderately to Severely Active Ulcerative Colitis Achieved Clinical Response with TREMFYA^®▼ (guselkumab) at 12 Weeks

 

Data from the Phase 2b QUASAR Induction Study 1 showed approximately 60 percent of patients achieved the primary endpoint of clinical response, and approximately 30 percent of patients showed endoscopic improvement with guselkumab treatment compared with placebo

 

Results also showed a greater proportion of guselkumab-treated patients achieved clinical remission and other major secondary endpoints at week 12 compared with placebo

 

BEERSE, BELGIUM, 18 February, 2022 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from the Phase 2b QUASAR Induction Study 1. Results showed a significantly greater proportion of adults with moderately to severely active ulcerative colitis (UC) who previously had an inadequate response or intolerance to conventional therapies and/or selected advanced therapies and were treated with TREMFYA^®▼ (guselkumab) achieved clinical response^a at week 12, the study’s primary endpoint (intravenous [IV] guselkumab 200 mg: 61.4 percent [62/101] and IV guselkumab 400 mg: 60.7 percent [65/107]) compared with placebo (27.6 percent [29/105]).¹ Safety data at week 12 were consistent with the safety profile for guselkumab in approved indications.^1,2 Guselkumab is not currently approved for the treatment of adults with UC in the European Union (EU).²

 

These new efficacy and safety data are the first reported on the investigational use of guselkumab for moderately to severely active UC in an analysis of 313 patients enrolled in the QUASAR clinical programme.^3,4 These findings were presented today as an oral presentation (OP23) at the 17^th Congress of the European Crohn’s and Colitis Organisation (ECCO), taking place virtually from 16-19 February.¹

 

“Despite available treatment options, there are patients with moderately to severely active ulcerative colitis who are still in need of additional therapeutic approaches due to inadequate response or intolerance to their current treatment,” said presenting study author Axel Dignass, M.D., Ph.D., Head of the Department of Medicine and Professor of Medicine and Gastroenterology at the Agaplesion Markus Hospital, Goethe University in Frankfurt, Germany.^b “Results from the QUASAR study show both IV induction doses of guselkumab achieved clinical responses in patients with moderately to severely active ulcerative colitis at rates greater than placebo.”

 

In the study, the primary endpoint of the clinical response is defined as a decrease from induction baseline in the modified Mayo score by ≥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.^1,c Major secondary endpoints in the QUASAR study include clinical remission,^d symptomatic remission,^e endoscopic improvement,^f histo-endoscopic mucosal improvement^g and endoscopic normalisation^h at week 12.^1,c 

 

Results from the five secondary endpoints showed:^1,c

• Clinical remission rates^d were achieved in 25.7 and 25.2 percent of patients in the 200 and 400 mg guselkumab groups, respectively, compared with 9.5 percent in the placebo group.
• Symptomatic remission rates^e were achieved in 50.5 and 47.7 percent of patients in the respective 200 and 400 mg guselkumab groups compared with 20.0 percent in the placebo group.
• Endoscopic improvement rates^f were achieved in 30.7 and 30.8 percent of patients in the respective 200 and 400 mg guselkumab groups compared with 12.4 percent in the placebo group.
• Histo-endoscopic mucosal improvement rates^g were achieved in 19.8 and 27.1 percent of patients in the respective 200 and 400 mg guselkumab groups compared with 8.6 percent in the placebo group.
• Endoscopic normalisation rates^h were achieved in 17.8 and 14 percent of patients in the respective 200 and 400 mg guselkumab groups compared with 6.7 percent in the placebo group.

 

Safety findings for both guselkumab dose groups were consistent with the known safety profile for guselkumab in approved indications.^1,2 The proportions of patients reporting adverse events (AEs), serious AEs, and AEs leading to discontinuation in both guselkumab dose groups were not greater compared with placebo.¹ No serious infections, cases of malignancy or death were reported for guselkumab.¹

 

“Data from the Phase 2b QUASAR study provide the initial evidence in the development of guselkumab as a potential treatment for adult patients with moderately to severely active ulcerative colitis,” said Jan Wehkamp, M.D., Ph.D., Vice President, Gastroenterology Disease Area Leader, Janssen Research & Development, LLC. “We look forward to advancing this important research in the ongoing QUASAR Phase 3 induction and maintenance studies as we continue in our commitment to develop therapeutic options for patients with debilitating diseases like ulcerative colitis.”

 

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Editor’s Notes:

1. Clinical response is defined as a decrease from induction baseline in the modified Mayo score by ≥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 1.¹ Modified Mayo score is a three-component (stool frequency, rectal bleeding, and endoscopy subscores) Mayo score without the physician’s global assessment.⁵
2. Professor Dr. Dignass is a paid consultant for Janssen. He has not been compensated for any media work.
3. Please see the ‘About QUASAR Induction Study 1’ section below for further details regarding the study design.
4. Clinical remission is defined as a stool frequency subscore of 0 or 1, a rectal bleeding score of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.¹
5. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0, where the stool frequency subscore has not increased from induction baseline.¹
6. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.¹
7. Histo-endoscopic mucosal improvement is defined as achieving a combination of histologic improvement (neutrophil infiltration in <5 percent of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system) and endoscopic improvement.¹
8. Endoscopic normalisation is defined as an endoscopy subscore of 0.¹

 

About QUASAR Induction Study 1 (NCT04033445; EudraCT 2018-004002-25)^3,4
QUASAR Induction Study 1 is a 12-week, double-blind, randomised, placebo-controlled, multicentre Phase 2b induction dose-ranging study evaluating the efficacy and safety of guselkumab in adults with moderately to severely active UC with inadequate response/intolerance to conventional therapies (thiopurines or corticosteroids) and/or advanced therapies (TNFa antagonists, vedolizumab, or tofacitinib). Participants had to have a baseline modified Mayo score of 5 to 9 (inclusive), with a Mayo rectal bleeding subscore ≥1 and a Mayo endoscopy subscore ≥2 obtained during central review of video endoscopy.

 

Participants were randomised equally into three groups receiving treatment at weeks 0, 4 and 8 with either guselkumab IV dosed at 200 or 400 mg, or matched placebo.¹

 

About Ulcerative Colitis

UC affects up to 2.6 million people in Europe.⁶ It is a chronic disease of the large intestine, also known as the colon, in which the lining becomes inflamed and develops tiny open sores, or ulcers, that produce pus and mucous.⁷ UC is the result of an abnormal response by the body's immune system.⁷ Symptoms vary, but may include loose and more urgent bowel movements, persistent diarrhoea, abdominal pain, bloody stools, loss of appetite, weight loss, and fatigue.^7,8

 

About TREMFYA^® (guselkumab)²

Developed by Janssen, guselkumab is the first approved fully human monoclonal antibody that selectively binds to the p19 subunit of interleukin (IL)-23 and inhibits its interaction with the IL-23 receptor. Guselkumab is approved in the EU for the treatment of moderate to severe plaque psoriasis (Pso) in adults who are candidates for systemic therapy, and alone or in combination with methotrexate (MTX) for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug therapy.² It is also approved in the U.S., Canada, Japan, and a number of other countries worldwide for the treatment of adults with moderate to severe plaque Pso who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light), and for the treatment of adult patients with active PsA.²

 

 

The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to TREMFYA^®.

 

GUSELKUMAB IMPORTANT SAFETY INFORMATION

In controlled periods of clinical studies with guselkumab, adverse drug reactions (ADRs) that consisted of respiratory tract infections were very common (≥10 percent); increased transaminases, headache, diarrhoea, arthralgia, and injection site reactions were common (≥1 to <10 percent); and herpes simplex infections, tinea infections, gastroenteritis, decreased neutrophil count, hypersensitivity, anaphylaxis, urticaria and rash were uncommon ADRs (≥0.1 percent to <1 percent).²

 

Please refer to the Summary of Product Characteristics for full prescribing information for guselkumab in Pso and PsA: https://www.ema.europa.eu/en/documents/product-information/tremfya-epar-product-information_en.pdf

 

ADRs should be reported▼. This medicinal product is subject to additional monitoring and it is, therefore, important to report any suspected AEs related to this medicinal product. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. ADRs should also be reported to Janssen-Cilag Ltd on +44 (0) 1494 567447.

 

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

 

Learn more at www.janssen.com/EMEA.

Follow us at www.twitter.com/JanssenEMEA.

 

Janssen-Cilag International NV, the marketing authorisation holder for TREMFYA^® in the EU, and Janssen Research & Development, LLC are each part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

 

Cautions Concerning Forward-Looking Statements

This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding TREMFYA^® (guselkumab) product development. 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 materialise, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, any of the other Janssen Pharmaceutical Companies 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 behaviour 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 January 2, 2022, 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 the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

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References

 

1. Dignass A, et al.The Efficacy and Safety of Guselkumab Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Phase 2b QUASAR Study Results Through Week 12 (OP23). Presented at the 2022 ECCO Congress, February 16-19, 2022.
2. European Medicines Agency. TREMFYA Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/medicine/34321. Accessed February 2022.
3. gov. A Study of Guselkumab in Participants With Moderately to Severely Active Ulcerative Colitis (QUASAR). Identifier: NCT04033445. Available at:  https://www.clinicaltrials.gov/ct2/show/record/NCT04033445. Accessed February 2022.
4. EU Clinical Trials Register. A Phase 2b/3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Protocol to Evaluate the Efficacy and Safety of Guselkumab in Participants with Moderately to Severely Active Ulcerative Colitis. EudraCT: 2018-004002-25. Available at: https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-004002-25/ES. Accessed February 2022.
5. Ulcerative Colitis: Clinical Trial Endpoints Guidance for Industry DRAFT GUIDANCE. Available at: https://www.fda.gov/files/drugs/published/Ulcerative-Colitis--Clinical-Trial-Endpoints-Guidance-for-Industry.pdf. Accessed February 2022.
6. Ng SC, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. The Lancet 2017;390:2769-78.
7. Crohn's & Colitis UK. What is Ulcerative Colitis? Available at: https://www.crohnsandcolitis.org.uk/about-crohns-and-colitis/publications/ulcerative-colitis. Accessed February 2022.
8. Crohn’s & Colitis Foundation. Living with Ulcerative Colitis. Available at: https://www.crohnscolitisfoundation.org/sites/default/files/legacy/assets/pdfs/living-with-ulcerative.pdf. Accessed February 2022.

 

CP-288338

February 2022