The Lancet Publishes Results from Phase 3 Induction and Maintenance Programs Evaluating Upadacitinib in Ulcerative Colitis

ABBVie (NYSE: ABBV) today announced The Lancet published results from three pivotal Phase 3 clinical trials U-ACHIEVE (induction), U-ACCOMPLISH and U-ACHIEVE (maintenance) evaluating upadacitinib (RINVOQ ® ) in patients with moderately to severely active ulcerative colitis who have had inadequate response, lost response or were intolerant to conventional or biologic therapy.

Data from the three studies formed the basis of the company's application for approval by regulatory agencies. The publication reports the efficacy and safety results of the two induction studies and a maintenance study evaluating clinical remission and endoscopic improvement with oral upadacitinib versus placebo over 8 weeks and 52 weeks, respectively. ¹

The use of upadacitinib for ulcerative colitis is not approved in the European Union and its safety and efficacy remain under review by the global health 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. ^2,3 The hallmark signs and symptoms of ulcerative colitis include rectal bleeding, abdominal pain, bloody diarrhea, tenesmus (a sense of pressure), urgency and fecal incontinence. ^{2 ,4} The severity of symptoms and unpredictability of disease course can lead to substantial burden and often disability among those living with the disease. ⁵ 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. ^3,6

About the U-ACHIEVE Induction, U-ACCOMPLISH and U-ACHIEVE Maintenance Studies ^6,7-10

The three Phase 3 studies are multicenter, randomized, 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 subjects with moderate to severe ulcerative colitis. Topline results of the U-ACHIEVE induction study were announced in December 2020 , topline results of the second induction study, U-ACCOMPLISH, were announced in February 2021 , and topline results of the U-ACHIEVE maintenance study were announced in June 2021 . More information can be found on https://www.clinicaltrials.gov (NCT03006068, NCT03653026, NCT02819635).

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. ^{11 -17} Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3, and TYK-2. ¹² The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.

RINVOQ is approved in the EU for rheumatoid arthritis, atopic dermatitis, axial spondyloarthritis and psoriatic arthritis. Phase 3 trials of RINVOQ in axial spondyloarthritis, Crohn's disease, giant cell arteritis and Takayasu arteritis are ongoing. ^{12 - 18}

RINVOQ (upadacitinib) U.S. Use and Important Safety Information ¹⁸

RINVOQ is a prescription medicine used:

• To treat adults with moderately to severely active ulcerative colitis when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
  
• To treat adults with moderate to severe rheumatoid arthritis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
  
• To treat adults with active psoriatic arthritis when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.

It is not known if RINVOQ is safe and effective in children with juvenile idiopathic arthritis, psoriatic arthritis, or with ulcerative colitis.

• To treat adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis ) that did not respond to previous treatment and their eczema is not well controlled with other pills or injections, including biologic medicines, or when the use of other pills or injections is not recommended.

RINVOQ is safe and effective in children 12 years of age and older weighing at least 88 pounds (40 kg) with atopic dermatitis.

It is not known if RINVOQ is safe and effective in children under 12 years of age with atopic dermatitis.

What is the most important information I should know about RINVOQ?

RINVOQ may cause serious side effects, including:

• Serious infections. RINVOQ can lower your ability to fight infections. Serious infections have happened while 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 healthcare provider (HCP) should test you for TB before starting RINVOQ and check you closely for signs and symptoms of TB during treatment with RINVOQ. You should not start taking RINVOQ if you have any kind of infection unless your HCP tells you it is okay. If you get a serious infection, your HCP may stop your treatment until your infection is controlled. You may be at higher risk of developing shingles (herpes zoster).
  
• Increased risk of death in people 50 years and older who have at least 1 heart disease (cardiovascular) risk factor.
  
• Cancer and immune system problems. RINVOQ may increase your risk of certain cancers. Lymphoma and other cancers, including skin cancers, can happen. Current or past smokers are at higher risk of certain cancers, including lymphoma and lung cancer. Follow your HCP's advice about having your skin checked for skin cancer during treatment with RINVOQ. Limit the amount of time you spend in sunlight. Wear protective clothing when you are in the sun and use sunscreen.
  
• Increased risk of major cardiovascular (CV) events, such as heart attack, stroke, or death, in people 50 years and older who have at least 1 heart disease (CV) risk factor, especially if you are a current or past smoker.
  
• Blood clots: Blood clots in the veins of the legs or lungs and arteries can happen with RINVOQ. This may be life-threatening and cause death. Blood clots in the veins of the legs and lungs have happened more often in people who are 50 years and older and with at least 1 heart disease (CV) risk factor.
  
• Allergic reactions. Symptoms such as rash (hives), trouble breathing, feeling faint or dizzy, or swelling of your lips, tongue, or throat, that may mean you are having an allergic reaction have been seen in people taking RINVOQ. Some of these reactions were serious. If any of these symptoms occur during treatment with RINVOQ, stop taking RINVOQ and get emergency medical help right away.
  
• Tears in the stomach or intestines and changes in certain laboratory tests. 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.

Do not take RINVOQ if:

• You are allergic to upadacitinib or any of the ingredients in RINVOQ.

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.
• Are a current or past smoker.
• Have had a heart attack, other heart problems, or stroke.
• Have had any type of cancer, hepatitis B or C, shingles (herpes zoster), 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 red or white blood cell counts, diabetes, chronic lung disease, HIV, or a weak immune system.
• Live, have lived, or have traveled to parts of the country, such as the Ohio and Mississippi River valleys and the Southwest, that increase your risk of getting certain kinds of fungal infections. If you are unsure if you've been to these types of 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 findings in 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 during treatment with RINVOQ and for 4 weeks after your last dose.
• Are breastfeeding or plan to breastfeed. RINVOQ may pass into your breast milk. Do not breastfeed during treatment with RINVOQ and for 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

If you are not sure if you are taking any of these medicines, ask your HCP or pharmacist.

What should I do or 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
• Get emergency help right away if you have any symptoms of a heart attack or stroke while taking RINVOQ, including:
• Discomfort in the center of your chest that lasts for more than a few minutes or that goes away and comes back
• Severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
• Pain or discomfort in your arms, back, neck, jaw, or stomach
• Shortness of breath with or without chest discomfort
• Breaking out in a cold sweat
• Nausea or vomiting
• Feeling lightheaded
• Weakness in one part or on one side of your body
• Slurred speech
• Tell your HCP right away if you have any signs or symptoms of blood clots during treatment with RINVOQ, including:
• Swelling
• Pain or tenderness in one or both legs
• Sudden unexplained chest or upper back pain
• Shortness of breath or difficulty breathing
• Tell your HCP right away if you 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), shingles (herpes zoster), herpes simplex virus infections (including cold sores), bronchitis, nausea, cough, fever, acne, headache, increased blood levels of creatine phosphokinase, allergic reactions, inflammation of hair follicles, stomach-area (abdominal) pain, increased weight, flu, tiredness, lower number of certain types of white blood cells (neutropenia, lymphopenia), muscle pain, flu-like illness, rash, increased blood cholesterol levels, and increased liver enzyme levels.

Separation or tear to the lining of the back part of the eye (retinal detachment) has happened in people with atopic dermatitis treated with RINVOQ. Call your HCP right away if you have any sudden changes in your vision during treatment with RINVOQ.

These are not all the possible side effects of RINVOQ.

How should I take RINVOQ?

RINVOQ is taken once a day with or without food. Do not split, crush, or chew the tablet. Take RINVOQ exactly as your HCP tells you to use it. RINVOQ is available in 15 mg, 30 mg and 45 mg extended-release tablets.

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 our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com . Follow @abbvie on Twitter , Facebook , LinkedIn or Instagram .

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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¹ S. Danese, et al. Upadacitinib as Induction and Maintenance Therapy for for Moderately to Severely Active Ulcerative Colitis: Results from the Phase 3, Multicentre, Double-Blind, Randomised Trials. Lancet.

² Gajendran M., et al. A comprehensive review and update on ulcerative colitis. Dis Mon. 2019 Dec;65(12):100851. doi: 10.1016/j.disamonth.2019.02.004. Epub 2019 Mar 2 .

³ The Facts about Inflammatory Bowel Diseases. Crohn's & Colitis Foundation of America. 2014. Available at: https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf . Accessed on March 29, 2022 .

⁴ Ulcerative colitis. Symptoms and Causes. Mayo Clinic. 2020. Available at: https://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/symptoms-causes/syc-20353326 . Accessed on March 29, 2022 .

⁵ Mehta F. Report: economic implications of inflammatory bowel disease and its management. Am J Manag Care. 2016 Mar;22(3 Suppl):s51-60.

⁶ Monstad, I., et al. Clinical course and prognosis in ulcerative colitis: results from population-based and observational studies. Ann Gastroenterol. 2014; 27(2): 95–104.

⁷ Vermeire, S., et al. OP23 Efficacy and safety of upadacitinib as induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from phase 3 U-ACCOMPLISH study, Journal of Crohn's and Colitis, Volume 15, Issue Supplement 1 . May 2021 .

⁸ Danese, S., et al. OP24 Efficacy and safety of upadacitinib induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from the phase 3 U-ACHIEVE study, Journal of Crohn's and Colitis, Volume 15, Issue Supplement 1. May 2021 .

⁹ Danese, S., et al. OP08 The effects of maintenance therapy with upadacitinib on abdominal pain, bowel urgency, and fatigue in patients with moderately to severely active Ulcerative Colitis: Phase 3 U-ACHIEVE maintenance results, Journal of Crohn's and Colitis , Volume 16, Issue Supplement 1. January 2022 .

¹⁰ A Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UC). ClinicalTrials.gov 2021. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02819635 . Accessed on March 29, 2022 .

¹¹ RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; September 2021 . Available at: https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.

¹² Pipeline – Our Science | AbbVie. AbbVie. 2021. Available at: https://www.abbvie.com/our-science/pipeline.html . Accessed on March 29, 2022 .

¹³ A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis (Heads Up). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03738397 . Accessed on March 29, 2022 .

¹⁴ A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373 . Accessed on March 29, 2022 .

¹⁵ A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of ABT-494 for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Immunomodulators or Anti-TNF Therapy. ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649 . Accessed on Accessed on March 29, 2022 .

¹⁶ A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202 . Accessed on March 29, 2022 .

¹⁷ A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (TAK) (SELECT-TAK). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04161898 . Accessed on March 29, 2022 .

¹⁸ RINVOQ [package insert]. North Chicago, IL : AbbVie Inc.; 2022.

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