Second Phase 3 Induction Study Confirms Upadacitinib (RINVOQ®) Improved Clinical and Endoscopic Outcomes in Patients with Crohn’s Disease

NORTH CHICAGO, Ill., Feb. 24, 2022 /PRNewswire/ --AbbVie (NYSE: ABBV) today announced positive top-line results from U-EXCEL, a Phase 3 induction study, showing upadacitinib (45 mg once daily) achieved both primary endpoints of clinical remission^a,b and endoscopic response^c at week 12.¹ U-EXCEL is the second of two Phase 3 induction studies to evaluate the safety and efficacy of upadacitinib in adults with moderate to severe Crohn’s disease who had an inadequate response or were intolerant to conventional or biologic therapy.¹

“The results from this study reaffirm the data from U-EXCEED and demonstrate the potential impact that upadacitinib could have on clinical and endoscopic outcomes in patients with moderate to severe Crohn’s disease,” said Michael Severino, M.D., vice chairman and president, AbbVie. “Our decades of collaboration with the gastroenterology community demonstrates AbbVie’s commitment to the discovery and development of multiple treatment options for patients with inflammatory bowel diseases.”

U-EXCEL included the same primary and key secondary endpoints as U-EXCEED, with clinical remission measured by the Crohn’s Disease Activity Index (CDAI) and by the patient-reported symptoms of stool frequency/abdominal pain (SF/AP).¹ A significantly greater proportion of patients treated with a 12-week induction regimen of upadacitinib 45 mg daily achieved clinical remission per CDAI at week 12 compared to placebo (49 percent versus 29 percent; p<0.0001).¹ Similar results were observed with clinical remission per SF/AP (51 percent in upadacitinib-treated patients versus 22 percent in placebo-treated patients; p<0.0001).¹ At week 12, a significantly greater proportion of patients treated with upadacitinib 45 mg achieved endoscopic response compared to the placebo group (46 percent versus 13 percent; p<0.0001).¹

Consistent with results from the U-EXCEED induction study, a significantly higher proportion of patients receiving upadacitinib 45 mg also achieved steroid-free clinical remission^d per CDAI and per SF/AP compared to placebo at week 12 among patients taking corticosteroids at baseline.¹ Early symptom improvement measured by CR-100 (defined as reduction of CDAI ≥100 points from baseline) at week two as well as clinical remission at week four were also achieved by a significantly higher proportion of patients receiving upadacitinib 45 mg.¹

“It is impressive to see the meaningful response that was achieved in this study in patients with moderate to severe Crohn’s disease who have had inadequate response to an immunosuppressant or a biologic,” said Edward V. Loftus Jr., M.D., professor of medicine in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minnesota, and U-EXCEL study investigator. “These results suggest that upadacitinib may help patients who are unable to control their disease, including symptoms and intestinal inflammation, despite prior conventional or biologic treatment options.”

During the 12-week, double-blind, placebo-controlled period, the safety profile of upadacitinib 45 mg was consistent with the safety profile observed in previous studies across indications, with no new safety risks observed.¹ The most common adverse events were acne and anemia in the upadacitinib 45 mg group.¹ Serious adverse events occurred in 6.9 percent of patients in the upadacitinib 45 mg group compared to 6.8 percent of patients in the placebo group.¹ Rates of serious infections were 1.1 percent in patients treated with upadacitinib 45 mg and 1.7 percent in those who received placebo.¹ Herpes zoster was reported in 2.9 percent of patients treated with upadacitinib 45 mg, all cases were nonserious.¹ There were no cases of adjudicated gastrointestinal perforation or death during the placebo-controlled period.¹ One case of adjudicated major cardiovascular event (MACE) was reported in the placebo group.¹

Patients who were on upadacitinib 45 mg and did not achieve clinical response at week 12 were included in an additional 12-week treatment cohort with upadacitinib 30 mg.¹ In this cohort, one patient died of COVID-19.¹ Patients who were on placebo and did not achieve clinical response at week 12 were included in a 12-week treatment cohort with upadacitinib 45 mg.¹ Among these patients, there was one case of adjudicated gastrointestinal perforation.¹

In U-EXCEL, no treatment-emergent cases of adjudicated MACE, malignancy or adjudicated venous thromboembolic event were reported in patients on upadacitinib treatment.¹

Full results from the U-EXCEL study will be presented at upcoming medical conferences and published in a peer-reviewed medical journal. Top-line results from the Phase 3 portion of the first induction study, U-EXCEED, were announced in December 2021 and the maintenance study for both is ongoing. Use of upadacitinib in Crohn’s disease is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

^dSteroid-free clinical remission is defined as clinical remission (per CDAI <150, or per SF/AP with average daily SF ≤2.8 and not worse than baseline and average daily AP score ≤1 and not worse than baseline) and discontinuation of corticosteroid use among patients taking corticosteroids at baseline.

About Crohn’s Disease

Crohn’s disease is a chronic, systemic disease that manifests as inflammation within the gastrointestinal (or digestive) tract, causing persistent diarrhea and abdominal pain.^15-17 It is a progressive disease, meaning it gets worse over time in a substantial proportion of patients.^16,17 Because the signs and symptoms of Crohn’s disease are unpredictable, it causes a significant burden on people living with the disease—not only physically, but also emotionally and economically.¹⁸

About U-EXCEL^1,14

The U-EXCEL study is the second of two Phase 3, multicenter, randomized, double-blind, placebo-controlled induction studies designed to evaluate the efficacy and safety of upadacitinib 45 mg induction treatment in adults with moderate to severe Crohn’s disease. U-EXCEL enrolled patients who had inadequately responded to or are intolerant to one or more conventional and/or biologic therapies.

The study included slightly different sets of primary and secondary endpoints for the U.S. Food and Drug Administration (FDA) and the EU European Medicines Agency (EMA). The primary endpoints were achievement of clinical remission (per CDAI for the U.S. FDA, and per SF/AP for the EU EMA, which was measured by average daily stool frequency and abdominal pain score) and endoscopic response (per SES-CD) at week 12. More information can be found on www.clinicaltrials.gov (NCT03345849).

About the Upadacitinib Phase 3 Crohn’s Disease Program^14,19,20

The global upadacitinib Phase 3 program evaluates more than 1,000 patients with moderate to severe Crohn’s disease across two induction studies and a maintenance study. These studies include assessments of efficacy, safety and tolerability of upadacitinib. More information on these trials can be found at www.clinicaltrials.gov (NCT03345836, NCT03345849, NCT03345823).

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.^6-14,21 Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3, and TYK-2.²¹ The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.

In the U.S., RINVOQ 15 mg and 30 mg is approved for use in adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable. RINVOQ 15 mg is also approved in the U.S. for adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers as well as adults with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers. In the EU, RINVOQ 15 mg is approved for the treatment of adults with moderate to severe active rheumatoid arthritis, adults with active psoriatic arthritis and adults with active ankylosing spondylitis. RINVOQ is also approved in the EU for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate to severe atopic dermatitis.

Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.^7-14 The use of upadacitinib in Crohn’s disease is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

RINVOQ^® (upadacitinib) U.S. Use and Important Safety Information²¹

RINVOQ is a prescription medicine used to treat:

• Adults with moderate to severe rheumatoid arthritis when 1 or more tumor necrosis factor (TNF) blockers have been used and did not work well or could not be tolerated.
• Adults with active psoriatic arthritis when 1 or more tumor necrosis factor (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 under 18 years of age with juvenile idiopathic arthritis or psoriatic arthritis.

• Adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis) who did not respond to previous treatment and whose 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 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 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, low white blood cell count (neutropenia), muscle pain, and flu-like illness.

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, break, crush, or chew the tablet. Take RINVOQ exactly as your HCP tells you to use it. RINVOQ is available in 15 mg and 30 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 http://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, 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 2021 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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