U.S. FDA Approves RINVOQ® (upadacitinib) as a Once-Daily Pill for Moderately to Severely Active Crohn’s Disease in Adults

The co-primary endpoints of endoscopic response (visible reduction of intestinal lining damage) and clinical remission were achieved by significantly more patients treated with RINVOQ (upadacitinib) at week 12 and week 52 versus placebo¹
Clinical response was achieved by significantly more patients treated with RINVOQ (upadacitinib) versus placebo as early as week 2 in induction studies¹
This indication marks the seventh FDA approval for RINVOQ across gastroenterology, rheumatology and dermatology¹

NORTH CHICAGO, Ill., May 18, 2023 – AbbVie (NYSE: ABBV) today announced that the U.S. Food and Drug Administration (FDA) has approved RINVOQ® (upadacitinib) for the treatment of adults with moderately to severely active Crohn’s disease who have had an inadequate response or intolerance to one or more TNF blockers.¹ This is the seventh FDA approval for RINVOQ across rheumatology, dermatology, and gastroenterology, where it is now indicated in both ulcerative colitis and Crohn’s disease.¹

“AbbVie recognizes the need for more treatment options for Crohn’s disease that can help address both rapid relief of symptoms along with the visible reduction of intestinal lining damage,” said Thomas Hudson, M.D., senior vice president of research and development, chief scientific officer, AbbVie. “We’re pleased that RINVOQ may provide this relief and is now available to treat Crohn’s disease.”

Endoscopic Response and Clinical Remission
The approval is supported by data from two induction studies, U-EXCEED and U-EXCEL, and the U-ENDURE maintenance study.¹ Statistical significance was achieved for the co-primary endpoints and key secondary endpoints with RINVOQ 45 mg in the induction studies and RINVOQ 15 mg and 30 mg in the maintenance study compared to placebo.

Endoscopic response: In the two induction studies, 34% and 46% of patients treated with RINVOQ 45 mg achieved endoscopic response (defined as a decrease of greater than 50% from the baseline Simplified Endoscopic Score for CD [SES-CD] or for patients with isolated ileal disease and a baseline SES-CD of 4, at least a 2-point reduction from baseline) at week 12, respectively, compared to 3% and 13% of patients receiving placebo.¹ In the maintenance study, 28% and 41% of patients treated with RINVOQ 15 mg and 30 mg achieved endoscopic response at week 52, respectively, compared to 7% of patients receiving placebo.
Clinical remission: In the two induction studies, 36% and 46% of patients treated with RINVOQ 45 mg achieved clinical remission (defined as a Crohn’s Disease Activity Index [CDAI] of less than 150) at 12 weeks, respectively, compared to 18% and 23% of patients receiving placebo. Additionally, in the maintenance trial, 42% and 55% of patients treated with RINVOQ 15 mg and 30 mg achieved clinical remission at 52 weeks, respectively, compared to 14% of patients receiving placebo.¹

“Symptoms of moderately to severely active Crohn’s disease can be disruptive and uncomfortable for patients, so relief as early as possible is key. Given the progressive nature of the disease, endoscopic response is just as important,” 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.* “Based on the clinical trial results, treatment with RINVOQ shows both early and long-term symptom relief along with evidence of a visible reduction of damage to the intestinal lining caused by excess inflammation.”

“I started feeling better within a couple weeks. My symptoms lessened – less cramping, firmer stools, and the bleeding stopped. When I stopped bleeding, I had more energy,” said Danielle, who is living with Crohn’s disease and received RINVOQ in an open-label treatment arm in one of the clinical trials.

Rapid Clinical Response and Corticosteroid-free Clinical Remission¹

Onset of clinical response based on CDAI was observed as early as two weeks in U-EXCEED and U-EXCEL, with a greater proportion of patients achieving clinical response at week 2 in RINVOQ-treated patients compared with placebo.¹
This is the first clinical program of an approved moderate-to-severe Crohn’s disease treatment to require steroid taper during the induction period, with a corticosteroid taper regimen initiated at week 4. Corticosteroid-free clinical remission (defined as discontinuation of steroid and achievement of clinical remission per CDAI [CDAI less than 150]) among patients on steroid at baseline was achieved at week 12 by more patients treated with RINVOQ in U-EXCEED and U-EXCEL (30% and 40%, respectively) compared to placebo (11% and 13%, respectively). In U-ENDURE, corticosteroid-free remission (defined as no corticosteroids for 90 days prior to week 52 and achievement of clinical remission) was achieved by more patients treated with RINVOQ 15 mg and 30 mg (42% and 53%, respectively) compared to 14% with placebo.

RINVOQ Safety Considerations¹

Overall, the safety profile observed in patients with Crohn’s disease treated with RINVOQ was consistent with the known safety profile for RINVOQ in other indications.
RINVOQ may cause serious side effects, including:

Serious infections. RINVOQ can lower ability to fight infections. Serious infections, some fatal, occurred, including tuberculosis (TB) and infections caused by bacteria, fungi, or viruses.
Increased risk of death in people age 50+ with at least 1 heart disease risk factor.
Cancer and immune system problems. Increased risk of some cancers, including lymphoma and skin. Current or past smokers have higher risk for lymphoma and lung cancer.
Increased risk of major cardiovascular events such as heart attack, stroke, or death in people 50+ with at least 1 heart disease risk factor, especially in current or past smokers.
Blood clots, some fatal, in veins of the legs or lungs and arteries. This occurred more often in people 50+ with at least 1 heart disease risk factor.
Serious allergic reactions. Do not take if allergic to RINVOQ or its ingredients.
Tears in the stomach or intestines; changes in certain laboratory test results.

For more information about RINVOQ, visit RINVOQ.com.

Patient Access & Support
AbbVie is committed to helping people access RINVOQ and other medicines, including offering a patient support program and a co-pay card that may reduce out-of-pocket costs to $5 per month for eligible, commercially insured patients. For those with limited or no health insurance, AbbVie offers myAbbVie Assist, a patient assistance program that provides RINVOQ at no charge to those who qualify. For more details, please visit AbbVie.com/myAbbVieAssist.

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.^2-4 It is a progressive disease, meaning it gets worse over time, and in many cases leads to surgery.^3,4 Because the signs and symptoms of Crohn’s disease are unpredictable, it causes a significant burden on people living with the disease.⁵

About the U-EXCEED and U-EXCEL Induction and the U-ENDURE Maintenance Studies^{1, 6-8}
The three Phase 3 studies are multicenter, randomized, double-blind, placebo-controlled studies to evaluate the efficacy and safety of RINVOQ 45 mg as induction therapy and RINVOQ 15 mg and 30 mg as maintenance therapy in patients with moderately to severely active Crohn’s disease. Topline results of the U-EXCEED and U-EXCEL induction studies were announced in December 2021 and February 2022. Topline results of the U-ENDURE maintenance study were announced in May 2022. More information can be found on https://clinicaltrials.gov (U-EXCEED: NCT03345836, U-EXCEL: NCT03345849, U-ENDURE: NCT03345823).

*Dr. Loftus is a consultant and advisor for AbbVie.

About RINVOQ® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a selective JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3, and TYK-2.¹ The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known.

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.^9-17

RINVOQ (upadacitinib) U.S. Uses and Important Safety Information¹

RINVOQ is a prescription medicine used to treat:

Adults with moderate to severe rheumatoid arthritis (RA) when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
Adults with active psoriatic arthritis (PsA) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
Adults with active ankylosing spondylitis (AS) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
Adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation when a TNF blocker medicine has been used, and did not work well or could not be tolerated.
Adults with moderate to severe ulcerative colitis (UC) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
Adults with moderate to severe Crohn’s disease (CD) 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, ankylosing spondylitis, non-radiographic axial spondyloarthritis, ulcerative colitis, or Crohn’s disease.

Adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis [AD]) that did not respond to previous treatment and their eczema is not well controlled with other pills or injections, including biologic medicines, or 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. This happens most often in people who take nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids. Get medical help right away if you get stomach-area pain, fever, chills, nausea, or vomiting.
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. See the Medication Guide or Consumer Brief Summary for a complete list of ingredients.

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.
There is a pregnancy surveillance program for RINVOQ. The purpose of the program is to collect information about the health of you and your baby. If you become pregnant while taking RINVOQ, you are encouraged to report the pregnancy by calling 1-800-633-9110.
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 avoid while taking RINVOQ?
Avoid food or drink containing grapefruit during treatment with RINVOQ as it may increase the risk of side effects.

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 other possible side effects of RINVOQ?
Common side effects 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, leukopenia), muscle pain, flu-like illness, rash, increased blood cholesterol levels, increased liver enzyme levels, pneumonia, low number of red blood cells (anemia), and infection of the stomach and intestine (gastroenteritis).

A 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.

Some people taking RINVOQ may see medicine residue (a whole tablet or tablet pieces) in their stool. If this happens, call your healthcare provider.

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 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
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 2022 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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