Results of Novel Clinical Study Show Adults with Moderately to Severely Active Ulcerative Colitis Achieved Higher Rates of Clinical Response, Clinical Remission, and Endoscopic Improvement at 12 Weeks with Guselkumab▼ and Golimumab Combination Therapy Versus Either Monotherapy Alone

Results of Novel Clinical Study Show Adults with Moderately to Severely Active Ulcerative Colitis Achieved Higher Rates of Clinical Response, Clinical Remission, and Endoscopic Improvement at 12 Weeks with Guselkumab▼ and Golimumab Combination Therapy Versus Either Monotherapy Alone

 

The VEGA Phase 2a proof-of-concept study shows 83.1 percent of patients who received combination therapy achieved the primary endpoint of clinical response and 36.6 percent of patients achieved clinical remission at week 12

 

The VEGA study represents a first-of-its-kind biologic combination assessment of an interleukin (IL)-23p19 subunit antagonist with a tumour necrosis factor-alpha (TNFα) antagonist in ulcerative colitis

 

BEERSE, BELGIUM, 19 February, 2022 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced data from a Phase 2a clinical trial that showed the combination of guselkumab▼, an interleukin (IL)-23p19 subunit antagonist, and golimumab, a tumour necrosis factor-alpha (TNFα) antagonist, induced higher rates of clinical response,^a clinical remission,^b endoscopic improvement,^c and a composite histologic-endoscopic endpoint^c,d at 12 weeks than either treatment alone in adults with moderately to severely active ulcerative colitis (UC).¹ Rates of adverse events (AEs) were comparable among treatment groups.¹ Detailed results of the VEGA trial were presented today as an oral presentation (OP36) at the 17th Congress of the European Crohn’s and Colitis Organisation (ECCO) taking place virtually from 16-19 February.¹ Guselkumab as well as the combination of guselkumab and golimumab are not currently approved for the treatment of adults with UC in the European Union (EU).

 

“There remains an unmet need for patients who are struggling with ulcerative colitis,” said presenting study author Bruce E. Sands, M.D., M.S., Chief of the Dr. Henry D. Janowitz Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai, and the Mount Sinai Hospital.^e “The initial VEGA study results combining IL-23p19 and TNFα antagonists are encouraging as we continue the development of this potential treatment option for moderately to severely active ulcerative colitis.”

 

VEGA 12-week study results show:¹

• Clinical response:^a A greater proportion of patients who received combination therapy of guselkumab and golimumab achieved the primary endpoint of clinical response^a at week 12 (83.1 percent [59/71]) versus 74.6 percent (53/71) of patients who received guselkumab alone, or 61.1 percent (44/72) of those who received golimumab alone.¹
• Clinical remission:^b 6 percent (26/71) of patients in the combination group achieved clinical remission^b based on the full Mayo score at week 12 versus 21.1 percent (15/71) and 22.2 percent (16/72) in the guselkumab and golimumab groups, respectively.¹ Additionally, 46.5 percent (33/71) of patients in the combination group achieved clinical remission^b based on the modified Mayo score at week 12 versus 23.9 percent (17/71) and 25 percent (18/72) in the guselkumab and golimumab groups, respectively.¹ 
• Endoscopic outcomes:
  • A higher proportion of patients who received combination therapy achieved endoscopic improvement^c (49.3 percent [35/71]) at week 12 compared with those who received either monotherapy (guselkumab: 29.6 percent [21/71]; golimumab: 25 percent [18/72]).¹
  • Percentages of patients with endoscopic normalisation^f were nearly double with combination therapy versus either monotherapy (combination therapy: 18.3 percent [13/71]; guselkumab: 8.5 percent [6/71]; golimumab: 9.7 percent [7/72]).¹
• Composite histologic-endoscopic outcomes:
  • 8 percent (29/71) of patients in the combination group achieved the composite endpoint of histologic remission^d and endoscopic improvement^c versus 26.8 percent (19/71) and 15.3 percent (11/72) in the guselkumab and golimumab groups, respectively.¹
  • Percentages of patients with both histologic remission^d and endoscopic normalisation^f were double with combination therapy versus either monotherapy (combination therapy: 15.5 percent [11/71]; guselkumab: 7 percent [5/71]; golimumab: 4.2 percent [3/72]).¹

 

Symptomatic remission^g (based on patient reports of rectal bleeding and stool frequency [SF]), histologic remission,^d and biomarker normalisation (calprotectin, C-reactive protein) rates at week 12 were also greater in the combination group.¹ Rates of key safety events were similar among treatment groups.¹ In the combination group, the guselkumab group, and the golimumab group, AEs occurred in 40.8 percent (29/71), 43.7 percent (31/71), and 52.8 percent (38/72), respectively.¹ Serious adverse events occurred in 1.4 percent (1/71), 2.8 percent (2/71), and 1.4 percent (1/72), respectively.¹ Infections were reported in 14.1 percent (10/71) in each of the combination and guselkumab groups and in 22.2 percent (16/72) of the golimumab group.¹ No deaths, malignancies, or tuberculosis cases were reported through week 12 of the study. One patient receiving combination therapy experienced concurrent serious infections of influenza and sepsis.¹

 

“Results from the VEGA study, a first-of-its-kind assessment of an IL-23p19 subunit antagonist combined with a TNFα antagonist in ulcerative colitis, allow us to further explore and identify the areas of unmet need that exist for patients,” said Jan Wehkamp, M.D., Ph.D., Vice President, Gastroenterology Disease Area Leader, Janssen Research & Development, LLC. “We are encouraged about the insights we will gain for future combination studies, as they can help to inform our pursuit to redefine treatment paradigms for people living with immune-mediated conditions like ulcerative colitis."

 

The next step for Janssen in studying combination therapy in UC is the Phase 2b DUET-UC study, which is a one-year dose-ranging study comparing combination therapy with monotherapy.

 

Editor’s Notes:

1. Primary endpoint of clinical response is defined as a decrease from baseline in the Mayo score ≥30 percent and ≥3 points, with either a decrease in rectal bleeding subscore ≥1 or rectal bleeding subscore of 0 or 1.¹
2. Major secondary endpoint of clinical remission is based on the full Mayo score and is defined as Mayo score ≤2, with no individual subscore >1. Using the modified Mayo score, clinical remission is defined as a Mayo SF subscore of 0 or 1, where the SF subscore has not increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.¹
3. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.¹
4. Histologic remission is defined as absence of neutrophils from the mucosa (both lamina propria and epithelium), no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system.¹
5. Sands is a paid consultant for Janssen. He has not been compensated for any media work.
6. Endoscopic normalisation is an endoscopy subscore of 0 with no friability present on the endoscopy.¹
7. Symptomatic remission is defined as Mayo SF subscore of 0 or 1, where the SF subscore has not increased from baseline, and a rectal bleeding subscore of 0.¹

 

 

 

About VEGA (NCT03662542; EudraCT 2018-001510-15)^2,3

VEGA is a randomised, double-blind, active-controlled, parallel group, global multicentre Phase 2a proof-of-concept study evaluating the efficacy and safety of combination therapy with guselkumab and golimumab in patients with moderately to severely active UC as defined by a Mayo score of 6 to 12 inclusive and an endoscopy subscore of >=2.

 

Study participants were naïve to TNFα antagonists and had to be refractory or intolerant to conventional therapy (e.g., immunomodulators and/or corticosteroids). Participants were randomly assigned to receive guselkumab dosed at 200 mg intravenous (IV) at weeks 0, 4, and 8 (n=71); golimumab dosed at 200 mg subcutaneous (SC) at week 0, then 100 mg SC at weeks 2, 6, and 10 (n=72); or combination with guselkumab dosed at 200 mg IV plus golimumab dosed at 200 mg SC at week 0, golimumab dosed at 100 mg SC at weeks 2, 6, and 10, and guselkumab dosed at 200 mg IV at weeks 4 and 8 (n=71).

 

The primary endpoint was clinical response at week 12, defined as a decrease from baseline in the Mayo score ≥30 percent and ≥3 points, with either a decrease in rectal bleeding subscore ≥1 or rectal bleeding subscore of 0 or 1. The major secondary endpoint was clinical remission at week 12, defined as Mayo score ≤2, with no individual subscore >1. No adjustments were made for multiple comparisons. Other key endpoints evaluated at week 12 were clinical remission (based on components of the modified Mayo score), symptomatic remission, endoscopic improvement, endoscopic normalisation, histologic remission, composite histologic-endoscopic endpoints, and biomarker outcomes.

 

About Ulcerative Colitis

UC affects up to 2.6 million people in Europe.⁴ It 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.⁵ UC is the result of an abnormal response by the body's immune system.⁶ Symptoms vary, but may include loose and more urgent bowel movements, persistent diarrhoea, abdominal pain, bloody stool, loss of appetite, weight loss, and fatigue.⁶

 

About Guselkumab⁷

Developed by Janssen, guselkumab (marketed under the brand name TREMFYA^®) is the first approved fully human monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor.⁷ 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 (DMARD).⁷ 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.⁷

 

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).⁷

 

Please refer to the Summary of Product Characteristics for full prescribing information for guselkumab in plaque 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 Golimumab⁸

Golimumab (marketed under the brand name SIMPONI^®), in combination with MTX, is a prescription medicine for adults with:

• Moderate to severe, active rheumatoid arthritis (RA) when the response to DMARD therapy including MTX has been inadequate.
• Severe active and progressive RA not previously treated with MTX.
• Active and progressive PsA, alone or in combination with MTX, when the response to previous DMARD therapy has been inadequate.

 

Golimumab alone is also a prescription medicine for adults with:

• Moderately to severely active UC in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.
• Severe active ankylosing spondylitis in adults who have responded inadequately to conventional therapy.
• Severe active non-radiographic axial spondyloarthritis with objective signs of inflammation, as indicated by elevated C-reactive protein and/or magnetic resonance imaging evidence, who have had an inadequate response to or are intolerant to nonsteroidal anti-inflammatory drugs.

 

Merck & Co., Inc. hold rights to market golimumab in the European Economic Area, the United Kingdom, Switzerland, Turkey, Russia, Serbia, Montenegro, Bosnia and Herzegovina, North Macedonia, and Albania. The Janssen Pharmaceutical Companies of Johnson & Johnson maintain marketing rights to golimumab in the U.S. and in all other countries or regions where golimumab is approved.

 

GOLIMUMAB IMPORTANT SAFETY INFORMATION

In controlled periods of clinical studies with golimumab, ADRs that consisted of upper respiratory tract infections were very common (≥10 percent); bacterial and viral infections, lower respiratory tract infections, bronchitis, sinusitis, superficial fungal infections, abscess, leukopenia, anaemia, allergic reactions, depression, insomnia, hypertension, dizziness, headache, paraesthesia, pyrexia, asthenia, injection site reactions, pruritus, rash, alopecia and dermatitis were common (≥1 to <10 percent); and sepsis, pyelonephritis, neoplasms, thrombocytopenia, pancytopenia, thyroid disorders, visual disorders, balance disorders, conjunctivitis, arrhythmia, ischaemic coronary artery disorders, bullous skin reactions, Pso, urticaria, cholelithiasis, hepatic disorders, interstitial lung disease, constipation, gastro-oesophageal reflux, breast and menstrual disorders were uncommon ADRs (≥0.1 percent to <1 percent).⁸

 

Please refer to the Summary of Product Characteristics for full prescribing information for golimumab: https://www.ema.europa.eu/en/documents/product-information/simponi-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 ADRs 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 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. Sands BE, et al. Efficacy and Safety of Combination Induction Therapy with Guselkumab and Golimumab in Participants with Moderately-to-Severely Active Ulcerative Colitis: Results Through Week 12 of a Phase 2a Randomized, Double-blind, Active-controlled, Parallel-group, Multicenter, Proof-of-concept Study (Abstract OP36). Presented at the 17th Congress of the European Crohn’s and Colitis Organisation (ECCO), 16-19 February 2022.
2. gov. A Study of Efficacy and Safety of Combination Therapy With Guselkumab and Golimumab in Participants With Moderately to Severely Active Ulcerative Colitis (VEGA). Identifier: NCT03662542. Available at: https://clinicaltrials.gov/ct2/show/NCT03662542. Accessed February 2022.
3. EU Clinical Trials Register. A Phase 2a Randomized, Double-blind, Active-controlled, Parallel-group, Multicenter, Proof-of-concept Clinical Study to Evaluate the Efficacy and Safety of Combination Therapy With Guselkumab and Golimumab in Participants With Moderately to Severely Active Ulcerative Colitis. Available at: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-001510-15. Accessed February 2022.
4. 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.
5. Crohn’s & Colitis Foundation. What is Ulcerative Colitis? Available at: https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis. Accessed February 2022.
6. Crohn’s & Colitis Foundation. Signs and Symptoms of Ulcerative Colitis. Available at: https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis/symptoms. Accessed February 2022.
7. European Medicines Agency. TREMFYA Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/medicine/34321. Accessed February 2022.
8. European Medicines Agency. SIMPONI Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/simponi-epar-product-information_en.pdf. Accessed February 2022.

 

CP-288360

February 2022