Upadacitinib Met the Primary and All Secondary Endpoints in the 52-Week Phase 3 Maintenance Study in Ulcerative Colitis Patients

ABBVie (NYSE: ABBV) today announced that upadacitinib (15 mg or 30 mg, once daily) met the primary endpoint of clinical remission (per Adapted Mayo Score) and all secondary endpoints at one-year (week 52) in the Phase 3 ulcerative colitis maintenance study. 1 Significantly more upadacitinib-treated patients achieved clinical remission at week 52 compared to placebo (15 mg: 42 percent and 30 mg: 52 percent versus placebo: 12 percent; p

"Ulcerative colitis is a disease with unpredictable symptoms and frequent flares, which can make daily life challenging," said Michael Severino , M.D., vice chairman and president, AbbVie. "We are encouraged by these results that demonstrate upadacitinib's potential as a treatment option for patients with moderate to severe ulcerative colitis."

In this study, adults with moderate to severe ulcerative colitis who achieved a clinical response (per partial Adapted Mayo Score) following an 8-week study period of once-daily upadacitinib (45 mg) induction treatment were re-randomized to receive upadacitinib 15 mg, upadacitinib 30 mg or placebo for an additional 52 weeks. ¹

All secondary endpoints were met, including the achievement of endoscopic improvement, histologic-endoscopic mucosal improvement (HEMI) and corticosteroid-free clinical remission at week 52. ¹ 49 percent of patients treated with upadacitinib 15 mg and 62 percent of patients treated with upadacitinib 30 mg achieved endoscopic improvement at 52 weeks versus 14 percent of patients in the placebo group (p 1 In addition, 35 percent of patients on upadacitinib 15 mg and 49 percent of patients on upadacitinib 30 mg achieved HEMI compared to 12 percent of patients in the placebo group (p 1 Of patients who were in remission at the completion of the 8-week induction studies, corticosteroid-free remission was achieved in 57 percent of patients in the upadacitinib 15 mg group and 68 percent of patients in the upadacitinib 30 mg group compared to 22 percent of patients in the placebo group (p 1

"Ulcerative colitis is a challenging disease to manage, and many patients do not find relief from their most burdensome symptoms," said Remo Panaccione , M.D., professor of medicine and director of the IBD unit, University of Calgary . "These positive results demonstrate upadacitinib's potential to achieve improvements in clinical, endoscopic and histological outcomes at 52 weeks. This is promising news for the IBD community."

A total of 746 patients who completed the 8-week upadacitinib induction treatment with clinical response and received at least one dose of the study drug in the maintenance period were included in the safety analysis. ¹ The safety results of upadacitinib (15 mg or 30 mg) were consistent with the safety profile observed in the Phase 3 induction studies in ulcerative colitis, as well as in previous studies across indications. ^1-6 No new safety risks were identified. ^1-6 The most common adverse events observed in the upadacitinib groups during the 52-week study period were nasopharyngitis, exacerbation of ulcerative colitis and blood creatine phosphokinase increase. ¹ The exposure-adjusted event rates of adverse events per 100 patient years were 16.0 events in the upadacitinib 15 mg group, 13.8 events in the upadacitinib 30 mg group and 26.1 events in the placebo group. ¹ The rates of infections were 6.2, 3.9 and 7.5 events per 100 patient years in the upadacitinib 15 mg, upadacitinib 30 mg and placebo groups, respectively. ¹ The rates of adverse events leading to treatment discontinuation per 100 patient years were 7.6 events and 7.9 events in patients receiving upadacitinib 15 mg and upadacitinib 30 mg, respectively, compared with 24.3 events in the placebo group. ¹

Malignancies (excluding non-melanoma skin cancer) reported in the study included one event in the upadacitinib 15 mg group, two events in the upadacitinib 30 mg group and one event in the placebo group. ¹ Adjudicated thrombotic events were reported in the upadacitinib 15 mg group (two events of pulmonary embolism), 30 mg group (two events of deep vein thrombosis) and the placebo group (one event of ovarian vein thrombosis). ¹ One adjudicated major adverse cardiovascular event (MACE) was reported in the upadacitinib 30 mg group and one was reported in the placebo group. ¹ One patient in the placebo group experienced events of adjudicated gastrointestinal perforation. ¹ No deaths were reported. ¹

Full results from the Phase 3 maintenance study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal. Top-line results from the Phase 3 induction studies, U-ACHIEVE and U-ACCOMPLISH, were announced in December 2020 and February 2021 , respectively. Use of upadacitinib in ulcerative colitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

About Ulcerative Colitis

Ulcerative colitis is a chronic, idiopathic, immune-mediated inflammatory bowel disease (IBD) of the large intestine that causes continuous mucosal inflammation extending, to a variable extent, from the rectum to the more proximal colon. ^15,16 The hallmark signs and symptoms of ulcerative colitis include rectal bleeding, abdominal pain, bloody diarrhea, tenesmus (a sense of pressure), urgency and fecal incontinence. ^15,17 The disease course of ulcerative colitis varies between patients and can range from quiescent disease to chronic refractory disease, which in some cases can lead to surgery or complications, including cancer or death. ^16,18 The severity of symptoms and unpredictability of disease course can lead to substantial burden and often disability among those living with the disease. ¹⁹

About the Phase 3 Maintenance Study ^1,9

The Phase 3 maintenance study is an ongoing, Phase 3 multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of upadacitinib in patients with moderate to severe ulcerative colitis. Results from the induction studies, U-ACHIEVE and U-ACCOMPLISH, were announced in December 2020 and February 2021 , respectively. The objective of this maintenance study is to evaluate the efficacy and safety of upadacitinib 15 mg and 30 mg, once daily, as a maintenance therapy compared to the placebo group.

The primary endpoint was achievement of clinical remission (per Adapted Mayo Score) at week 52. Secondary endpoints included achievement of endoscopic improvement, HEMI and corticosteroid-free clinical remission at one-year. More information can be found on www.clinicaltrials.gov (NCT02819635).

About the Upadacitinib Ulcerative Colitis Program ^9,20,21

The global upadacitinib ulcerative colitis program evaluates more than 1,300 patients with moderately to severely active ulcerative colitis across three pivotal studies. These studies include assessments of efficacy and safety of upadacitinib. Key measures of efficacy include clinical remission (per Adapted Mayo Score), clinical response (per Adapted Mayo Score), endoscopic improvement and endoscopic response. More information on these trials can be found at www.clinicaltrials.gov (NCT02819635, NCT03653026, NCT03006068).

About Upadacitinib (RINVOQ ^® )

Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. ^7-14 In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2. ⁷ In August 2019, RINVOQ received U.S. FDA approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. RINVOQ is approved by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs); for the treatment of active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs; and for the treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy. The approved dose for RINVOQ is 15 mg. Phase 3 trials of RINVOQ in atopic dermatitis, axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing. ^9-14 Use of RINVOQ in ulcerative colitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

Important Safety Information about RINVOQ ^® (upadacitinib) ⁷

RINVOQ U.S. Use and Important Safety Information
RINVOQ is a prescription medicine used to treat adults with moderate to severe rheumatoid arthritis in whom methotrexate did not work well or could not be tolerated. It is not known if RINVOQ is safe and effective in children under 18 years of age.

What is the most important information I should know about RINVOQ?
RINVOQ is a medicine that can lower the ability of your immune system to fight infections. You should not start taking RINVOQ if you have any kind of infection unless your healthcare provider (HCP) tells you it is okay.

• Serious infections have happened in some people taking RINVOQ, including tuberculosis (TB) and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Your HCP should test you for TB before starting RINVOQ and check you closely for signs and symptoms of TB during treatment with RINVOQ. You may be at higher risk of developing shingles (herpes zoster).
• Lymphoma and other cancers, including skin cancers, can happen in people taking RINVOQ.
• Blood clots in the veins of the legs or lungs and arteries are possible in some people taking RINVOQ. This may be life-threatening and cause death.
• Tears in the stomach or intestines and changes in certain laboratory tests can happen. Your HCP should do blood tests before you start taking RINVOQ and while you take it. Your HCP may stop your RINVOQ treatment for a period of time if needed because of changes in these blood test results.

What should I tell my HCP BEFORE starting RINVOQ?
Tell your HCP if you:

• Are being treated for an infection, have an infection that won't go away or keeps coming back, or have symptoms of an infection such as:
• Fever, sweating, or chills
• Shortness of breath
• Warm, red, or painful skin or sores on your body
• Muscle aches
• Feeling tired
• Blood in phlegm
• Diarrhea or stomach pain
• Cough
• Weight loss
• Burning when urinating or urinating more often than normal
• Have TB or have been in close contact with someone with TB.
• Have had any type of cancer, hepatitis B or C, shingles (herpes zoster), or blood clots in the veins of your legs or lungs, diverticulitis (inflammation in parts of the large intestine), or ulcers in your stomach or intestines.
• Have other medical conditions including liver problems, low blood cell counts, diabetes, chronic lung disease, HIV, or a weak immune system.
• Live, have lived, or have traveled to parts of the country that increase your risk of getting certain kinds of fungal infections, such as the Ohio and Mississippi River valleys and the Southwest. If you are unsure if you've been to these areas, ask your HCP.
• Have recently received or are scheduled to receive a vaccine. People who take RINVOQ should not receive live vaccines.
• Are pregnant or plan to become pregnant. Based on animal studies, RINVOQ may harm your unborn baby. Your HCP will check whether or not you are pregnant before you start RINVOQ. You should use effective birth control (contraception) to avoid becoming pregnant while taking RINVOQ and for at least 4 weeks after your last dose.
• Are breastfeeding or plan to breastfeed. RINVOQ may pass into your breast milk. You should not breastfeed while taking RINVOQ and for at least 6 days after your last dose.

Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RINVOQ and other medicines may affect each other, causing side effects.

Especially tell your HCP if you take:

• Medicines for fungal or bacterial infections
• Rifampicin or phenytoin
• Medicines that affect your immune system

Ask your HCP or pharmacist if you are not sure if you are taking any of these medicines.

What should I tell my HCP AFTER starting RINVOQ?
Tell your HCP right away if you:

• Have any symptoms of an infection. RINVOQ can make you more likely to get infections or make any infections you have worse.
• Have any signs or symptoms of blood clots during treatment with RINVOQ, including:
• Swelling
• Sudden unexplained chest pain
• Pain or tenderness in the leg
• Shortness of breath
• Have a fever or stomach-area pain that does not go away, and a change in your bowel habits.

What are the common side effects of RINVOQ?
These include: upper respiratory tract infections (common cold, sinus infections), nausea, cough, and fever. These are not all the possible side effects of RINVOQ.

RINVOQ is taken once a day with or without food. Do not split, break, crush, or chew the tablet. Take RINVOQ exactly as your HCP tells you to use it.

This is the most important information to know about RINVOQ. For more information, talk to your HCP.   You are encouraged to report negative side effects of prescription drugs to the FDA. Visit https://www.fda.gov/medwatch or call 1-800-FDA-1088.

If you are having difficulty paying for your medicine, AbbVie may be able to help. Visit AbbVie.com/myAbbVieAssist to learn more.

Please click here for the Full Prescribing Information and Medication Guide .

Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Gastroenterology

With a robust clinical trial program, 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 on AbbVie in gastroenterology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/gastroenterology.html .

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, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com . Follow @abbvie on Twitter , Facebook , Instagram , YouTube and LinkedIn .

Forward-Looking Statements

Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2020 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

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