JANSSEN

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced new data showing treatment with a single intravenous (IV) dose of STELARA^® (ustekinumab) induces clinical remission and response in adults with moderate to severe ulcerative colitis (UC) who previously experienced an inadequate response or intolerance to conventional or biologic therapies. The findings will be presented today as part of the Late Breaking Abstract Plenary at the American College of Gastroenterology (ACG) Annual Scientific Meeting 2018.

Results from the induction phase of the Phase 3 UNIFI study show that treatment with a single IV dose of ustekinumab, at both doses studied, induced clinical remission in a significantly greater proportion of UC patients at Week 8 (15.6% of patients receiving 130 mg ustekinumab and 15.5% of patients receiving ~6 mg/kg ustekinumab) compared with placebo. Major secondary endpoints – including the proportion of patients in clinical response, endoscopic healing, as well as health-related quality of life scores – were significantly improved at week 8 among patients receiving ustekinumab compared with those receiving placebo. At least 50% of study participants were considered biologically refractory, and 17% had a history of inadequate response or intolerance to any anti-TNF antibody and vedolizumab.

“Ulcerative colitis is a complex immune disease, and more than half of the patients with ulcerative colitis have not experienced remission with currently available conventional or biologic treatment options,” said lead investigator Dr Bruce E. Sands, MD, Dr Burrill B. Crohn research institute, Professor of Medicine and Chief of the Dr Henry D. Janowitz Division of Gastroenterology at Mount Sinai School of Medicine. “The significant rates of remission observed in this refractory population through the 8-week induction, coupled with a safety profile that is well-documented through years of research and use in other immune diseases, demonstrate the potential for ustekinumab as an effective treatment for ulcerative colitis.”

Patients participating in the Phase 3 UNIFI study were randomised 1:1:1 at Week 0, and received a single IV dose of placebo, 130 mg ustekinumab, or ~6 mg/kg ustekinumab (weight tiered dosing: patients weighing ≤55kg received 260 mg; patients weighing >55kg and ≤85kg received 390 mg; and patients weighing >85kg received 520 mg). At Week 8, patients (n=961) were evaluated for clinical remission, endoscopic healing, clinical response, change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) score (a health-related quality of life measure for patients with IBD [Inflammatory Bowel Disease]), and mucosal healing (an endpoint that includes both endoscopic healing and histologic healing).

At Week 8:

• 15.6% of patients receiving 130 mg ustekinumab and 15.5% of patients receiving ~6 mg/kg ustekinumab achieved clinical remission, compared with 5.3% of patients receiving placebo (p<0.001). Remission was defined as a Mayo score ≤2 points, with no individual subscore >1¹
• 26.3% of patients receiving 130 mg ustekinumab and 27.0% of patients receiving ~6 mg/kg ustekinumab experienced endoscopic healing, compared with 13.8% of patients receiving placebo (p<0.001). Endoscopic healing was defined as a Mayo endoscopy subscore of 0 (normal mucosa or inactive disease) or 1 (mild disease activity)¹
• 51.3% of patients receiving 130 mg ustekinumab and 61.8% of patients receiving ~6 mg/kg ustekinumab achieved clinical response, compared with 31.3% of patients receiving placebo (p<0.001). Clinical response was defined as a decrease from baseline in the Mayo score by ≥30% and ≥3 points, with either a decrease from baseline in the rectal bleeding subscore ≥1 or a rectal bleeding subscore of 0 or 1¹
• Patients receiving 130 mg and ~6 mg/kg ustekinumab achieved statistically significant improvements from baseline IBDQ (31.5 and 31.0 respectively) compared with placebo (10.0) (p<0.001)¹

• 20.3% of patients receiving 130 mg ustekinumab and 18.4% of patients receiving ~6 mg/kg ustekinumab achieved mucosal healing compared with 8.9% of patients receiving placebo (p<0.001). Mucosal healing is defined as combined endoscopic healing (Mayo endoscopy subscore of 0 or 1) and histologic healing (defined as 0–<5% neutrophils in epithelium, no crypt destruction, and no erosions, ulcerations or granulations)¹

In addition, significant decreases in median levels of fecal calprotectin and lactoferrin were also observed at Week 8 (p<0.05).

Through Week 8, adverse events (AEs), serious AEs and infections (including serious infections) were reported in similar proportions across ustekinumab and placebo treatment groups. No malignancies, opportunistic infections or tuberculosis infections were reported through Week 8. One death from oesophageal varices haemorrhage was reported for a patient with no known history of cirrhosis or portal hypertension in the ~6 mg/kg dose group prior to Week 8.

“Ustekinumab is the first and only biologic that targets interleukin (IL)-12 and IL-23 cytokines, which are believed to play a role in immune-mediated diseases, like ulcerative colitis,” said Dr Philippe Szapary, MD, MSCE, Vice President, Clinical Development, Janssen Research & Development, LLC. “These induction data from the Phase 3 UNIFI study underscore the potential for this unique pathway in the treatment of ulcerative colitis, which may lead to a new effective and safe treatment option for ulcerative colitis patients in the future.”

In addition to the UNIFI study data, Janssen is also presenting results from the IM-UNITI open-label long-term extension (LTE) study for ustekinumab in the treatment of adults with moderate to severe Crohn’s disease, including an oral presentation on the long-term efficacy of ustekinumab, with and without concomitant immunosuppressants through two years. A poster demonstrating the long-term efficacy and safety of ustekinumab through three years of treatment will also be presented.

About the UNIFI trial

UNIFI is a Phase 3 protocol, designed to evaluate the safety and efficacy of ustekinumab induction and maintenance dosing for the treatment of moderate to severe ulcerative colitis in adults who demonstrated an inadequate response to, or were unable to tolerate, conventional (i.e., corticosteroids, immunomodulators) or biologic (i.e., one or more TNF blockers and/or vedolizumab) therapies. Both the induction and maintenance studies are randomised, double-blind, placebo-controlled, parallel group, multi-centre studies. The Induction study was of at least 8 weeks’ duration for each participant. Participants achieving clinical response in the induction study were eligible for the maintenance study. The maintenance study was 44 weeks’ in duration. The primary endpoint of the induction study was clinical remission at Week 8 and the primary endpoint for the maintenance study was clinical remission at Week 44 among responders to a single intravenous (IV) ustekinumab infusion. After completion of the maintenance study, a long-term extension study will follow eligible participants for an additional three years.

About ulcerative colitis

More than five million people worldwide are living with Crohn’s disease and ulcerative colitis — collectively known as Inflammatory Bowel Disease (IBD). Ulcerative colitis affects up to one million people in Europe.² 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 an abnormal response by the body's immune system. Symptoms vary, but may include loose and more urgent bowel movements, persistent diarrhoea, abdominal pain, bloody stool, loss of appetite, weight loss and fatigue.³

About STELARA ^® (ustekinumab)

In the European Union, ustekinumab is approved for the treatment of moderate to severe plaque psoriasis in adults who fail to respond, have a contraindication, or are intolerant to other systemic therapies, including ciclosporin, methotrexate (MTX), or psoralen plus ultraviolet A (PUVA). Ustekinumab is also indicated for the treatment of moderate to severe plaque psoriasis in adolescent patients from the age of 12 years and older, who are inadequately controlled by or are intolerant to other systemic therapies or phototherapies. In addition, ustekinumab is approved alone or in combination with MTX for the treatment of active psoriatic arthritis in adult patients when the response to previous non-biological disease-modifying antirheumatic drug (DMARD) therapy has been inadequate. In November 2016, the European Commission approved ustekinumab for the treatment of adult patients with moderately to severely active Crohn's disease, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a TNF-alpha antagonist or have medical contraindications to such therapies.

The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to ustekinumab, which is currently approved for the treatment of moderate to severe plaque psoriasis in 90 countries, paediatric psoriasis in 43 countries, psoriatic arthritis in 83 countries and Crohn’s disease in 62 countries.

Important safety information

For complete European Union (EU) prescribing information, please visit: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000958/human_med_001065.jsp&mid=WC0b01ac058001d124

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science.

We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com/emea . Follow us on Twitter: @JanssenEMEA.

Janssen-Cilag International NV is 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 development and potential availability in Europe of ustekinumab. 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-Cilag International NV, Janssen Pharmaceutical Companies of Johnson & Johnson and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges inherent in product research and development, including uncertainty of clinical success and obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; 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 1, 2017, including under “Item 1A. Risk Factors,” its most recently filed Quarterly Report on Form 10-Q, including under the caption “Cautionary Note Regarding Forward-Looking Statements,” 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. Neither 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, Sandborn WJ, Panaccione R et al . Safety and efficacy of ustekinumab induction therapy in patients with moderate to severe ulcerative colitis: results from the Phase 3 UNIFI study [abstract]. Presented at the American College of Gastroenterology (ACG) Annual Scientific Meeting, Philadelphia, Pennsylvania. 5–10 October 2018.

2. Janssen Disease Lens. Ulcerative colitis. Available at https://www.diseaselens.com/v2/index.php . (last accessed October 2018).

3. Crohn’s and Colitis Organisation. Ulcerative colitis. Available at https://www.crohnsandcolitis.org.uk/about-inflammatory-bowel-disease/ulcerative-colitis . (last accessed October 2018).

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