RINVOQ® (Upadacitinib) Receives Its Sixth U.S. FDA Approval

• RINVOQ is now approved as the first and only oral JAK inhibitor for adults with active non-radiographic axial spondyloarthritis (nr-axSpA)
• RINVOQ is the first and only JAK inhibitor approved for both active ankylosing spondylitis (AS) and nr-axSpA^1-3
• In a clinical study, RINVOQ delivered rapid and meaningful disease control based on patients achieving ASAS40 vs. placebo, as well as significant improvement in signs and symptoms of nr-axSpA at week 14^1,2

NORTH CHICAGO, Ill., October 21, 2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announces that the U.S. Food and Drug Administration (FDA) has approved RINVOQ® (upadacitinib 15 mg, once daily), an oral therapy, for the treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation who have had an inadequate response or intolerance to tumor necrosis factor (TNF) blocker therapy. This additional indication follows the FDA approval of RINVOQ in April of this year for adults with active ankylosing spondylitis (AS) who have had an inadequate response or intolerance to one or more TNF blockers, making it the first and only JAK inhibitor that is approved for both conditions.¹

Nr-axSpA is a chronic, progressive inflammatory rheumatic disease that causes joint inflammation, leading to back pain and stiffness, and cannot be detected by x-ray.^5,6 Nr-axSpA and AS are two sub-types of a broader condition called axial spondyloarthritis. Approximately five percent of patients with nr-axSpA will progress to AS after five years, and 19 percent will progress after ten years.⁷

“This latest FDA approval of RINVOQ in active nr-axSpA provides a new oral, once-daily treatment option for patients who historically have had limited treatment options for this painful, chronic disease,” said Thomas Hudson, M.D., senior vice president, research and development, chief scientific officer, AbbVie. “RINVOQ is now approved to treat patients across the spectrum of axial spondyloarthritis. This further underscores AbbVie’s commitment to advancing the standards of care for patients living with these diseases.”

The FDA approval decision is supported by data from the Phase 3 SELECT-AXIS 2 clinical trial, which assessed the efficacy, safety, and tolerability of RINVOQ in adults with active nr-axSpA. Among patients who received RINVOQ 15 mg, nearly half achieved an ASAS40* response, the primary endpoint, at week 14 compared to placebo (44.9 percent vs. 22.3 percent respectively).^{1, 2} ASAS40 responses were observed as early as two weeks in nr-axSpA patients treated with RINVOQ. The safety profile in patients with nr-axSpA treated with RINVOQ 15 mg was consistent with the safety profile in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.¹

“Many patients living with nr-axSpA continue to experience symptoms and are unable to control disease with current treatments. In the SELECT-AXIS 2 trials, RINVOQ demonstrated efficacy in both nr-axSpA and AS with safety that was consistent across indications,” said Atul Deodhar, M.D., professor of medicine and medical director of the Rheumatology Clinics for the Division of Arthritis and Rheumatic Diseases at Oregon Health & Science University, and lead investigator of the SELECT-AXIS 2 nr-axSpA trial. “Today’s FDA approval offers an important new therapeutic option for patients and their caregivers to help take control of their symptoms and disease.”

“There are limited treatment options for people living with nr-axSpA, a condition that can pose many challenges for patients and significantly impact their quality of life as their symptoms persist despite treatment," said Cassie Shafer, chief executive officer, Spondylitis Association of America (SAA). "This approval of RINVOQ is a tremendous step forward in providing our patient community with another option to help them reach their treatment goals, and to find relief.”

This FDA approval marks the sixth indication for RINVOQ in the United States across chronic immune-mediated diseases, including four in rheumatology.¹

Additional study results include the following:

Improvement in nr-axSpA Signs & Symptoms at Week 14^1,2

In the SELECT-AXIS 2 nr-axSpA trial, patients receiving RINVOQ 15 mg experienced greater improvements at week 14 compared to placebo in the individual components of the ASAS composite index, including total back pain, patient global assessment of disease activity, morning stiffness, and physical function. Multiplicity-controlled endpoints included total back pain and Bath Ankylosing Spondylitis Disease Activity Index (BASFI).

• A significantly greater mean decrease from baseline in Total Back Pain (-2.91 change from baseline) compared to those receiving placebo (-2.00).²
• A significantly greater improvement in physical function (-2.61 change from baseline) as assessed by mean change from baseline in BASFI compared to patients on placebo (-1.47).²

*ASAS40 is a composite index that measures disease activity.² To achieve an ASAS40 response, a patient's disease activity must have improved by at least 40%, as well as improved by two units (on a 0 to 10 scale) in at least three of four disease areas assessed, and the remaining area must not have gotten worse, including back pain, patient global assessment of disease activity, physical function, and morning stiffness.²

Other Health-Related Outcomes

Patients treated with RINVOQ 15 mg showed significant improvements in health-related quality of life as measured by Ankylosing Spondylitis Quality of Life (ASQoL) compared to placebo at Week 14.

Safety Considerations

• 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 SELECT-AXIS 2 trial program⁴
SELECT-AXIS 2 was conducted as a master study protocol that contains two standalone studies with randomization, data collection, analysis and reporting conducted independently. The Phase 3, randomized, placebo-controlled, double-blind studies are evaluating the efficacy and safety of RINVOQ compared with placebo on reduction of signs and symptoms in adult participants with active axial spondyloarthritis (axSpA), including bDMARD-IR AS (Study 1) and non-radiographic axial spondyloarthritis (nr-axSpA) (Study 2). More information on this trial can be found at https://www.clinicaltrials.gov/ (NCT04169373).

In the clinical trial, the primary endpoint was the percentage of subjects achieving an ASAS40 response after 14 weeks of treatment with RINVOQ versus placebo.

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.

In the U.S., RINVOQ 15 mg is approved for adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers; adults with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers; adults with active ankylosing spondylitis (AS) who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers and adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation who have had an inadequate response or intolerance to TNF blocker therapy.¹ RINVOQ 45 mg is approved for use in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more TNF blockers as an induction therapy once daily for 8 weeks. The recommended dose of RINVOQ for maintenance treatment is 15 mg once daily. A dosage of 30 mg once daily may be considered for patients with refractory, severe or extensive disease. Discontinue RINVOQ if an adequate response is not achieved with the 30 mg dose. Use the lowest effective dosage needed to maintain response. RINVOQ 15 mg once daily can also be initiated in adults and children 12 years of age and older weighing at least 40 kg 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. In these children and adults less than 65 years of age who do not achieve an adequate response, the dose may be increased to 30 mg once daily.

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.^4,8-14

U.S. Uses and Important Safety Information About RINVOQ® (upadacitinib) ¹

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 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 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.

It is not known if RINVOQ is safe and effective in children with juvenile idiopathic arthritis, psoriatic arthritis, ulcerative colitis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.

• 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 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. 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 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 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), muscle pain, flu-like illness, rash, increased blood cholesterol levels, and increased liver enzyme levels.

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.

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 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 Rheumatology
For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. 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 in order to help more people living with rheumatic diseases reach their treatment goals. For more information, visit AbbVie in rheumatology.

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 women's health, 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 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.

*Dr. Atul Deodhar, M.D., is a researcher/consultant for AbbVie.

References:

1. RINVOQ® (upadacitinib) [Package Insert]. North Chicago, Ill.: AbbVie Inc.
2. Deodhar A, Van den Bosch F, Poddubnyy D, et al. U Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet. 2022;400:369–79. doi:10.1016/S0140-6736(22)01212-0.
3. van der Heijde D, Baraliakos X, Sieper J, et al. Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomized, placebo-controlled phase 3 trial. Ann Rheum Dis. 2022;0:1–9. doi:10.1136/annrheumdis-2022-222608.
4. A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed October 21, 2022.
5. Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet 2017; 390: 73–84.
6. Deodhar AA, Understanding Axial Spondyloarthritis: A Primer for Managed Care. Am J Manag Care. 2019;25:S319-S330.
7. Wang R, Ward MM. Epidemiology of axial spondyloarthritis: an update. Curr Opin Rheumatol. 2018 Mar;30(2):137-143. doi: 10.1097/BOR.0000000000000475. PMID: 29227352; PMCID: PMC5811203.
8. A study comparing upadacitinib (ABT-494) to placebo and to adalimumab in adults with rheumatoid arthritis who are on a stable dose of methotrexate and who have an inadequate response to methotrexate (SELECT-COMPARE). ClinicalTrials.gov identifier: NCT02629159. Accessed October 21, 2022. https://www.clinicaltrials.gov/ct2/show/NCT02629159
9. A Study to Evaluate the Safety and Efficacy of ABT-494 for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed on October 21, 2022.
10. 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. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on October 21, 2022.
11. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed: October 21, 2022.
12. A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Participants With Psoriatic Arthritis Who Have an Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (SELECT - PsA 1). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on October 21, 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. Available at: https://clinicaltrials.gov/ct2/show/NCT03738397. Accessed: October 21, 2022.
14. A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (SELECT-TAK). ClinicalTrials.gov. Available at https://clinicaltrials.gov/ct2/show/record/NCT04161898. Accessed: October 21, 2022.

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