NICE Recommends RINVOQ[®]▼(upadacitinib) as a Treatment Option for Moderately to Severely Active Crohn’s Disease

PRESS RELEASE - For UK Consumer, Medical and Industry Trade Media Only

• Upadacitinib is the first janus kinase (JAK) inhibitor that will be available for the treatment of Crohn’s disease (CD) in England and Wales, offering a new option that is taken as a once daily pill to those who continue to have moderate to severe CD symptoms despite treatment with conventional or biological therapies¹

• CD is a chronic condition associated with inflammation of the digestive system.² Often first diagnosed in those aged 20-30,^2,3,4 it is estimated to affect over 155,000 adults in the UK.^5,6 CD diagnosis can lead to poor quality of life with a significant impact on people’s daily activities, as well as mental health difficulties^7,8,9,10,11

• The NICE recommendation is based on data from three Phase 3 clinical trials demonstrating upadacitinib achieved the coprimary endpoints of clinical remission and endoscopic response at week 12 and week 52 (p<0.001 vs placebo)^12,13,14,15

MAIDENHEAD, UK, 18 May 2023 – AbbVie (NYSE: ABBV) today announced that the National Institute for Health and Care Excellence (NICE) has issued positive Final Draft Guidance (FDG) recommending RINVOQ^® (upadacitinib) as an option for treating moderately to severely active Crohn’s disease (CD) in adults when the condition has not responded well enough or has lost response to a previous biological treatment, or when a previous biological treatment was not tolerated, or when tumour necrosis factor [TNF]-alpha inhibitors are contraindicated.¹

It is estimated that over 155,000 adults are living with the condition in the UK and almost half have moderate or severe CD.^5,6,16 CD is a chronic, progressive condition of the digestive system, associated with inflammation and mucosal ulceration.^2,17,18 Alongside ulcerative colitis, CD is one of the two main types of inflammatory bowel disease.¹⁸ Uncontrolled CD leads to inflammation of the digestive system and results in over 20% of people with the condition undergoing surgery within five years of diagnosis.^2,19 It is most commonly first diagnosed in those aged 20 to 30 and the number of people diagnosed is set to rise in the UK.^3,4,6

“The pain, physical symptoms and complications of Crohn’s disease should not be underestimated. Often starting at pivotal time during young adulthood, it can lead to low quality of life and have a significant impact on people’s daily activities and work, as well as having mental health consequences including depression and anxiety”, said Sarah Sleet, Chief Executive Officer, Crohn’s and Colitis UK. “It can be difficult for people with Crohn’s disease to find a suitable treatment that works for them or continues to work for them, so new options are of vital importance.”

“As a progressive disease, it is imperative that we help people with Crohn’s disease to achieve disease control and improve their quality of life.” said Dr Alexandra Kent, Consultant Gastroenterologist at King's College Hospital NHS Trust. “There has been a lack of new advanced therapies made available on the NHS to treat Crohn’s disease for over half a decade. Being able to offer eligible people an additional treatment option that is available as a once daily pill is a positive step forward.”

The NICE recommendation is based on data from three Phase 3 clinical trials, which demonstrated that significantly more patients treated with upadacitinib achieved the co-primary endpoints of clinical remission and endoscopic response, with clinical remission measured by the patient-reported symptoms of stool frequency/abdominal pain (SF/AP).^12,13,14,15

“We are pleased that NICE has recommended upadacitinib for eligible people with Crohn’s disease on the NHS in England and Wales. This is another important milestone for the inflammatory bowel disease community, as it follows NICE’s recommendation for upadacitinib in ulcerative colitis last year,” said Belinda Byrne, Medical Director, AbbVie UK. “We are committed to using our extensive immunology experience and working tirelessly to ensure as many people as possible with this debilitating condition can find a treatment that has the potential to have a significant impact on their life.”

The safety results of upadacitinib in U-EXCEED, U-EXCEL and U-ENDURE were generally consistent with the known safety profile of upadacitinib in other licensed indications.^12,13,14,15 In the placebo-controlled CD induction and maintenance clinical trials, the most commonly reported adverse events with upadacitinib 45 mg, 30 mg or 15 mg were upper respiratory tract infection, pyrexia, increased blood creatine phosphokinase, anaemia, acne, neutropaenia, rash, herpes zoster, pneumonia. hypercholesterolaemia, bronchitis, folliculitis, herpes simplex and influenza. The most common serious adverse events were serious infections.¹⁵

▼ This medicine is subject to additional monitoring. Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk or via the MHRA Yellow Card app, available in Google Play or Apple AppStores. Adverse events should also be reported to AbbVie at GBPV@abbvie.com.

-Ends-

UK media contacts:

Sophie Thompson                                          Hannah Morris

AbbVie UK                                                       GCI Health

T: +44 (0)7811 032320                                   T: +44 (0) 7910 257455

E: sophie.e.thompson@abbvie.com             E: hannah.morris@gcihealth.com

NOTES TO EDITORS:

About Crohn’s disease

Crohn’s disease (CD) is a chronic, progressive condition of the digestive system, associated with inflammation and mucosal ulceration.¹⁷ The pain, physical symptoms and complications of CD lead to low quality of life have a significant impact on people’s daily activities and work, and have mental health consequences including depression and anxiety.^7,8,9,10,11

Despite the availability of a range of treatments, not everyone with CD achieves long-lasting remission and the inflammation of the digestive system from disease flare-ups result in over 20% of people undergoing surgery within five years of diagnosis.¹⁹

It is estimated that there are over 155,000 adults living with the condition in the UK and 40% have moderate or severe CD.^5,6,16 As well as the significant impact on people with the condition, CD results in a substantial burden on healthcare systems. According to Hospital Episodes Statistics (HES) data there were 122,027 hospital admissions related to CD and 131,413 finished consultant episodes in 2020– 2021.²⁰

About upadacitinib

Upadacitinib is a janus kinase (JAK) inhibitor indicated for the treatment of certain people diagnosed with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, atopic dermatitis, non-radiographic axial spondyloarthritis, ulcerative colitis and Crohn’s disease.¹⁵

The JAK family of enzymes contains four members, JAK1, JAK2, JAK3 and TYK2, which work in pairs.¹⁵ In human cellular assays, upadacitinib preferentially inhibits signalling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.¹⁵ The relevance of the inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known.

For more information about upadacitinib please follow this link: https://www.medicines.org.uk/emc/product/10972/smpc

About the U-EXCEED, U-EXCEL induction and U-ENDURE maintenance phase 3 clinical trials¹⁵

The three Phase 3 studies are multicentre, randomised, double-blind, placebo-controlled studies to evaluate the efficacy and safety of upadacitinib 45 mg once daily as induction therapy, and upadacitinib 15 mg and 30 mg once daily as maintenance therapy in adults with moderately to severely active Crohn's disease. In all three studies, clinical remission (measured by the patient-reported symptoms of stool frequency/abdominal pain [SF/AP]) and endoscopic response were the co-primary endpoints.^12,13,14,15

In U-EXCEED, a significantly greater proportion of patients treated with a 12-week induction regimen of upadacitinib 45 mg daily achieved clinical remission per SF/AP at week 12 compared to placebo (40 percent, versus 14 percent; p<0.001) and endoscopic response compared to placebo (35 percent versus 4 percent; p<0.001).

U-EXCEL, the second of two Phase 3 induction studies, included the same primary and key secondary endpoints as U-EXCEED. A significantly greater proportion of patients treated with a 12-week induction regimen of upadacitinib 45 mg daily achieved clinical remission per SF/AP at week 12 compared to placebo (51 percent versus 22 percent; p<0.001) and endoscopic response compared to the placebo group (46 percent versus 13 percent; p<0.001). Both co-primary endpoints were met with statistical significance and upadacitinib also met most key secondary endpoints, consistent with findings from the first Phase 3 induction study, U-EXCEED.

In the U-ENDURE maintenance study, patients from U-EXCEED and U-EXCEL who responded to 12 weeks of upadacitinib 45 mg oral induction treatment were re-randomised to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo. In patients with moderate to severe Crohn's disease who achieved clinical remission per SF/AP with upadacitinib induction treatment, a significantly greater proportion treated with either 15 mg or 30 mg of upadacitinib achieved at week 52, compared to placebo:

• Clinical remission per SF/AP (36 and 46 percent, respectively, versus 14 percent in the placebo group (p<0.001))
• Endoscopic response (28 and 40 percent, respectively, versus 7 percent of patients who received placebo (p<0.001)

The safety results of upadacitinib in U-EXCEED, U-EXCEL and U-ENDURE were generally consistent with the known safety profile of upadacitinib in other licensed indications.^12,13,14,15 In the placebo-controlled CD induction and maintenance clinical trials, the most commonly reported adverse events with upadacitinib 45 mg, 30 mg or 15 mg were upper respiratory tract infection, pyrexia, increased blood creatine phosphokinase, anaemia, acne, neutropaenia, rash, herpes zoster, pneumonia. hypercholesterolaemia, bronchitis, folliculitis, herpes simplex and influenza. The most common serious adverse events were serious infections.¹⁵

More information on these trials can be found at www.clinicaltrials.gov (NCT03345836, NCT03345849, NCT03345823).

Upadacitinib is also for the treatment of certain people diagnosed with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, atopic dermatitis and ulcerative colitis.¹⁵

About AbbVie in gastroenterology

For more than 20 years, AbbVie has been dedicated to improving care for people living with immune disorders. Our longstanding commitment to discovering and delivering transformative therapies is underscored by our pursuit of cutting-edge science that improves our understanding of promising new pathways and targets to help more people living with inflammatory conditions reach their treatment goals.

AbbVie is committed to cutting-edge research to drive exciting developments in inflammatory bowel diseases (IBD), like ulcerative colitis and Crohn's disease. By innovating, learning and adapting, AbbVie aspires to eliminate the burden of IBD and make a positive long-term impact on the lives of people with IBD. For more information, please visit www.abbvie.co.uk.

About AbbVie

AbbVie’s mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, ’ and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.co.uk. Follow @abbvieuk on Twitter or YouTube.

UK-UPAD-230071 | May 2023