Janssen Presents Results of First Head-to-Head Study of Biologic Therapies in Patients with Moderate to Severe Crohn’s Disease

Janssen Presents Results of First Head-to-Head Study of Biologic Therapies in Patients with Moderate to Severe Crohn’s Disease

 

Late-breaker is one of 20 Janssen abstracts, 16 of which show the safety profile and efficacy of ustekinumab in treating Crohn’s disease and ulcerative colitis at Digestive Disease Week (DDW) Virtual 2021

BEERSE, BELGIUM, 24 May, 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced efficacy and safety data for STELARA^® (ustekinumab) in Crohn’s disease (CD) and ulcerative colitis (UC),^1-4 including data from the SEAVUE study, the first head-to-head study of biologic therapies in patients with CD, presented in a Clinical Science Late-Breaking Abstract Plenary session.¹ SEAVUE data showed treatment with ustekinumab^a demonstrated high rates of clinical remission, corticosteroid-free remission, clinical response and endoscopic response through one year in biologic-naïve patients with moderately to severely active CD, although the primary endpoint of statistical superiority versus adalimumab was not demonstrated.¹ These head-to-head data are one of 20 abstracts Janssen presented from the Company’s gastroenterology pipeline and portfolio at DDW Virtual 2021, which took place 21-23 May.^1-4

 

“As the first head-to-head study of biologic therapies in Crohn’s disease, SEAVUE is filling an important knowledge gap in the gastrointestinal community,” said Bruce E. Sands, M.D., M.S., Chief of the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai Hospital and the Dr. Burrill B. Crohn Professor of Medicine (Gastroenterology), at the Icahn Institute for Medicine at Mount Sinai, and SEAVUE study principal investigator.^b “SEAVUE has generated data that confirm ustekinumab as an important option for people living with moderately to severely active Crohn’s disease who are new to biologic therapy.”

 

Ustekinumab vs adalimumab efficacy and safety in biologic-naïve CD patients through one year (Presentation #775d):¹ The SEAVUE study examined a total of 386 patients with moderately to severely active CD.¹ Patients were randomised 1:1 to treatment with ustekinumab approximately 6 mg/kg intravenous (IV) at baseline, then 90 mg subcutaneous (SC) every eight weeks (q8w), or treatment with adalimumab 160/80 mg SC at baseline/week two, then 40 mg SC every two weeks per the US Food and Drug Administration-approved regimens without dose modifications.¹ Results did not show statistically significant differences:¹

• 64.9 percent of ustekinumab-treated patients and 61 percent of adalimumab-treated patients achieved clinical remission (Crohn’s Disease Activity Index [CDAI] <150) at one year (week 52), the study’s primary endpoint.¹
• Major secondary endpoints were not significantly different between the groups:¹
• 60.7 percent of ustekinumab-treated patients and 57.4 percent of adalimumab-treated patients achieved corticosteroid-free remission.¹
• 72.3 percent of ustekinumab-treated patients and 66.2 percent of adalimumab-treated patients achieved clinical response.¹
• 56.5 percent of ustekinumab-treated patients and 55.4 percent of adalimumab-treated patients achieved patient-reported outcome (PRO)-2 symptom remission.¹
• At week 16, 57.1 percent of ustekinumab-treated patients and 60 percent of adalimumab-treated patients achieved clinical remission.¹
• At week 52, in patients with Simple Endoscopic Score for Crohn’s Disease (SES-CD)^c ≥3 at baseline, 28.5 percent of ustekinumab-treated patients and 30.7 percent of adalimumab-treated patients achieved endoscopic remission.¹
• Benefits for both treatments were also demonstrated across additional efficacy endpoints, but did not demonstrate statistically significant differences:
• At week 52, in patients with SES-CD ≥3 at baseline, 41.9 percent of ustekinumab-treated patients and 36.9 percent of adalimumab-treated patients achieved endoscopic response.¹
• Clinical response achieved at week 16 was maintained at week 52 in 88.6 percent of ustekinumab-treated patients and 78 percent of adalimumab-treated patients.¹
• The mean change from baseline to week 52 in the number of liquid/soft stools in the prior seven days was -19.9 for ustekinumab-treated patients and -16.2 for adalimumab-treated patients. The mean change from baseline to week 52 in the sum of number of liquid/soft stools and abdominal pain scores in the prior seven days was -29.6 for ustekinumab-treated patients and -25.1 for adalimumab-treated patients.¹
• Safety results were consistent with prior experience for both treatments:
• Discontinuation rates were numerically lower for ustekinumab-treated patients (15.2 percent) versus adalimumab-treated patients (23.6 percent) who discontinued before week 52.
• Among ustekinumab-treated patients and adalimumab-treated patients, 6.3 percent and 11.3 percent had adverse events (AEs) that led to discontinuation of study drug, respectively.¹
• Adverse events were reported in 80.1 percent and 77.9 percent of patients receiving ustekinumab or adalimumab, respectively.¹
• Serious adverse events (SAEs) were reported in 13.1 percent and 16.4 percent of patients, including serious infections reported in 2.1 percent and 2.6 percent of patients receiving ustekinumab or adalimumab, respectively.¹
• Through week 52, one patient developed basal cell carcinoma of the skin after receiving adalimumab; no patient reported malignancies after receiving ustekinumab. No deaths were reported through week 52.¹

 

“Until now, there have been no head-to-head trials comparing the safety and efficacy of prescription biologics to treat Crohn’s disease, a chronic condition that can cause persistent and debilitating symptoms which can have a profound impact on a person's daily life,” said Andrew Greenspan, M.D., Vice President, Immunology Medical Affairs, Janssen Scientific Affairs, LLC. “Armed with this new clinical trial data, doctors have a compelling option in ustekinumab for appropriate patients living with Crohn’s disease.”

 

Additional abstracts are also being presented:

 

• Presentation #129: Sandborn W, et al. Safety of Ustekinumab in IBD: Pooled Safety Analysis Through 5 Years in CD and 2 Years in UC²
• Presentation #Sa576: Sandborn W, et al. Long-term (5-Year) Maintenance of Clinically Meaningful Improvement in Health-Related Quality of Life in Patients with Moderate to Severe Crohn’s disease Treated with Ustekinumab in the IM-UNITI Long-term Extension Study³
• Presentation #611: Johnson A, et al. The Real-World Effectiveness of Ustekinumab in the Treatment of Crohn’s Disease⁴

 

“We are pleased to continue to build upon and reinforce the strength of Janssen’s gastroenterology portfolio with our promise to advance treatment options for patients living with inflammatory bowel disease,” said Jan Wehkamp, M.D., Vice President, Gastroenterology Disease Area Leader, Janssen Research & Development, LLC. “The strong body of scientific evidence for ustekinumab is the result of our long-term commitment to studying ustekinumab comparatively and in a variety of clinical settings to provide doctors and their patients with data that can help inform treatment decisions.”

#ENDS#

Footnotes:

1. Per the US Food and Drug Administration-approved regimens of ustekinumab and adalimumab without dose modifications.¹
2. Dr Bruce Sands is a paid consultant for Janssen. He has not been compensated for any media work.
3. SES-CD evaluates the presence or absence of endoscopic healing of the intestinal mucosa. The SES-CD is scored based on four endoscopic variables (area of affected surface, presence and size of ulcers, extent of ulcerated surface, and presence of stenoses) in the five intestinal segments. The total SES-CD score range is 0–60, with each section ranging from 0 to 12 points.⁵

 

About DDW

Digestive Disease Week^® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is a fully virtual meeting from May 21-23, 2021. The meeting showcases more than 2,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at http://www.ddw.org.

 

About SEAVUE (NCT03464136; EudraCT 2017-004209-41)^6,7

SEAVUE is a Phase 3b, multicentre, randomised, blinded, active-controlled study to compare the efficacy and safety of ustekinumab to adalimumab in the treatment of biologic-naïve patients with moderately to severely active Crohn's disease. The study consists of screening (within 1 to 5 weeks prior to week 0), treatment phase (weeks 0 to 52), and follow-up phase (up to week 76). Study assessments include Crohn's Disease Activity Index (CDAI), video ileocolonoscopy; CD-related healthcare utilisation; patient-reported outcomes (PROs); laboratory evaluations; biomarkers; review of concomitant medications and adverse events (AEs); and evaluation of serum concentrations of study agent as well as development of antibodies to study agent. All participants were randomly assigned to receive either ustekinumab or adalimumab. No participants were treated with placebo only.

 

About IM-UNITI (NCT01369355; EudraCT 2010-022760-12)^8,9

IM-UNITI, a Phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel group study, evaluated the efficacy and safety of ustekinumab maintenance therapy in adult patients with moderate to severe CD. Patients who had responded to a single IV dose of ustekinumab in the UNITI-1 or UNITI-2 induction studies were randomised equally to receive maintenance SC ustekinumab 90 mg q8w or q12w, or placebo. There were 1,281 patients enrolled in the maintenance study. In randomised patients who met loss of response criteria between weeks 8–32, a one-time dose adjustment to 90 mg q8w occurred. All patients completing week 44 were eligible to enter the long-term extension program, continuing their current regimen up to week 252.

 

About Crohn’s disease

CD is one of the two main forms of inflammatory bowel disease, which affects up to two million people across Europe.¹⁰ CD is a chronic inflammatory condition of the gastrointestinal tract with no known cause, but the disease is associated with abnormalities of the immune system that could be triggered by a genetic predisposition, diet or other environmental factors.¹¹ Symptoms of CD can vary but often include abdominal pain and tenderness, frequent diarrhoea, rectal bleeding, weight loss and fever.^11,12 There is currently no cure for CD.¹³

 

About Ulcerative Colitis

UC affects up to 2.6 million people in Europe.¹⁰ 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.¹⁴ UC is the result of an abnormal response by the body's immune system.¹⁴ Symptoms vary, but may include loose and more urgent bowel movements, persistent diarrhoea, abdominal pain, bloody stools, loss of appetite, weight loss and fatigue.^14,15

 

About STELARA^® (ustekinumab)¹⁶

Ustekinumab is a fully human monoclonal antibody and is the first biologic treatment to selectively inhibit the interleukin (IL)-12 and IL-23 pathways.¹⁶ In the EU, ustekinumab is approved for the treatment of adult patients with moderate to severe CD who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a TNF-α antagonist, or have medical contraindications to such therapies.¹⁶ Ustekinumab is also approved for the treatment of adults with moderately to severely active UC who have had an inadequate response with, or lost response to, or were intolerant to either conventional therapy or a biologic, or have medical contraindications to such therapies.¹⁶ In addition to CD and UC, ustekinumab has been approved for the treatment of two further immune-mediated conditions in the EU: psoriasis and psoriatic arthritis.¹⁶

 

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

 

Important Safety Information¹⁶

The most common AEs (>5%) in controlled periods of clinical studies with ustekinumab were nasopharyngitis and headache. Most were considered to be mild and did not necessitate discontinuation of study treatment. The most serious adverse reaction that has been reported for ustekinumab is serious hypersensitivity reactions, including anaphylaxis. The overall safety profile is similar for adult patients with CD, UC, psoriasis, and psoriatic arthritis.¹⁶

Please refer to the Summary of Product Characteristics for full prescribing information for ustekinumab: https://www.ema.europa.eu/en/documents/product-information/stelara-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.

 

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 STELARA^® in the EU, and Janssen Research & Development, LLC, are 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 ongoing and planned development efforts involving STELARA^® (ustekinumab) in Crohn’s disease and ulcerative colitis. 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-Cilag International NV, 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 3, 2021, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, and the company’s subsequent 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 B, et al. Ustekinumab Versus Adalimumab for Induction and Maintenance Therapy in Moderate-to-Severe Crohn’s Disease: The SEAVUE Study. Presented at the 2021 Digestive Disease Week Virtual Meeting May 21-23.
2. Sandborn W, et al. Safety of Ustekinumab in IBD: Pooled Safety Analysis Through 5 Years in CD and 2 Years in UC. Presented at the 2021 Digestive Disease Week Virtual Meeting May 21-23.
3. Sandborn W, et al. Long-term (5-Year) Maintenance of Clinically Meaningful Improvement in Health-Related Quality of Life in Patients with Moderate to Severe Crohn’s disease Treated with Ustekinumab in the IM-UNITI Long-term Extension Study. Presented at the 2021 Digestive Disease Week Virtual Meeting May 21-23.
4. Johnson A, et al. The Real-World Effectiveness of Ustekinumab in the Treatment of Crohn’s Disease. Presented at the 2021 Digestive Disease Week Virtual Meeting May 21-23.
5. Klenske E, et al. “Targeting mucosal healing in Crohn’s disease: what the clinician needs to know." Therapeutic advances in gastroenterology 12 (2019): 1756284819856865.
6. Clinicaltrials.gov. Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year (SEAVUE). Identifier: NCT03464136. Available at: https://clinicaltrials.gov/ct2/show/study/NCT03464136. Accessed May 2021.
7. Clinicaltrialsregister.eu. A Phase 3b, Multicenter, Randomized, Blinded, Active-Controlled Study to Compare the Efficacy and Safety of Ustekinumab to that of Adalimumab in the Treatment of Biologic Naïve Subjects with Moderately-to-Severely Active Crohn’s Disease. Identifier: 2017-004209-41. Available at: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004209-41/ES. Accessed May 2021.
8. Clinicaltrials.gov. A Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Patients With Moderately to Severely Active Crohn's Disease (IM-UNITI). Identifier: NCT01369355. Available at: https://clinicaltrials.gov/ct2/show/NCT01369355. Accessed May 2021.
9. Clinicaltrialsregister.eu. A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Subjects with Moderately to Severely Active Crohn’s Disease. Identifier:    2010-022760-12. Available at: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-022760-12/DE. Accessed May 2021.
10. 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. Accessed May 2021.
11. Crohn’s and Colitis Foundation. Causes of Crohn’s disease. Available at: https://www.crohnscolitisfoundation.org/what-is-crohns-disease/causes. Accessed May 2021.
12. Crohn’s and Colitis Foundation. Crohn’s disease. Available at: https://www.crohnscolitisfoundation.org/what-is-crohns-disease/overview. Accessed May 2021.
13. Mayo Clinic. Crohn’s disease. Available at: https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304. Accessed May 2021.
14. Crohn's & Colitis UK. What is Ulcerative Colitis? Available at: https://www.crohnsandcolitis.org.uk/about-inflammatory-bowel-disease/ulcerative-colitis. Accessed May 2021.
15. Crohn’s & Colitis Foundation. ‘Living with Ulcerative Colitis’ leaflet. Available at: https://www.crohnscolitisfoundation.org/sites/default/files/legacy/assets/pdfs/living-with-ulcerative.pdf. Accessed May 2021.
16. European Medicines Agency. STELARA Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/stelara-epar-product-information_en.pdf. Accessed May 2021.