RINVOQ® Receives U.S. FDA Approval for Active Psoriatic Arthritis

- ABBVie (NYSE: ABBV) today announced that the U.S. Food and Drug Administration (FDA) has approved RINVOQ ® (upadacitinib; 15 mg, once daily) for the treatment of adults with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers. 1

"The efficacy of RINVOQ in relieving the many manifestations of psoriatic arthritis is well-characterized in two large, long term clinical studies," said Michael Severino , M.D., vice chairman and president, AbbVie. "This new approval underscores our mission to deliver a portfolio of therapies that can help more people with rheumatic diseases achieve disease control."

The FDA approval is supported by data from two pivotal Phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, which assessed the efficacy, safety and tolerability of RINVOQ in patients with PsA. ^2,3 In both studies, the safety profile in patients with active PsA treated with RINVOQ 15 mg was consistent with the safety profile observed in patients with rheumatoid arthritis.

"Many adults still struggle to find a treatment option that helps them lower their disease activity," said Iain McInnes , professor of medicine and Versus Arthritis professor of rheumatology at University of Glasgow , U.K., and lead investigator of the SELECT-PsA 1 trial. "With this FDA approval, RINVOQ has the potential to help more people find meaningful relief from the signs and symptoms of psoriatic arthritis that they see and feel and to help reach their treatment goals."

Across SELECT-PsA 1 and SELECT-PsA 2 Phase 3 clinical trials, RINVOQ met its primary endpoint of ACR20 at week 12 with patients taking RINVOQ 15 mg achieving significantly higher ACR20 responses (71% and 57%, respectively) versus placebo (36% and 24%, respectively). ^2,3

Joint Efficacy ^1-3

• Across both SELECT-PsA 1 and SELECT-PsA 2 Phase 3 clinical trials, patients treated with RINVOQ 15 mg achieved higher ACR50 responses (38% and 32%, respectively) at week 12 compared to placebo (13% and 5%, respectively).
• Patients treated with RINVOQ 15 mg across the SELECT-PsA 1 and SELECT-PsA 2 clinical trials achieved higher ACR70 responses (16% and 9%, respectively) compared to placebo (2% and 1%, respectively) at week 12.
• Treatment with RINVOQ 15 mg resulted in improvement in dactylitis and enthesitis in patients with pre-existing dactylitis or enthesitis.
• In SELECT-PsA 1, treatment with RINVOQ 15 mg significantly inhibited the progression of structural joint damage (-0.02 change from baseline) compared to placebo (0.23) as assessed by the change from baseline in modified Total Sharp Score (mTSS) at week 24.

Physical Function ^1-3

• Across SELECT-PsA 1 and SELECT-PsA 2 clinical trials, patients treated with RINVOQ 15 mg showed significant improvement in physical function from baseline compared to placebo as assessed by HAQ-DI at week 12.

Fatigue ^1-3

• In both Phase 3 clinical trials, patients receiving RINVOQ 15 mg experienced significantly greater improvement from baseline in fatigue, as measured by the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) score, at Week 12 compared to placebo.

Skin Response ^1-3

• Treatment with RINVOQ 15 mg resulted in improvement in skin manifestations in patients with PsA. However, RINVOQ has not been studied in and is not indicated for the treatment of plaque psoriasis.

Safety ^1-3

• Overall, the safety profile observed in patients with active PsA treated with RINVOQ 15 mg was consistent with the safety profile observed in patients with rheumatoid arthritis. During the 24-week placebo-controlled period, the most common adverse events reported with RINVOQ 15 mg were upper respiratory tract infection and blood creatine phosphokinase elevations. The frequencies of herpes zoster and herpes simplex were 1.1% and 1.4%, respectively, with RINVOQ 15 mg and 0.8% and 1.3%, respectively, with placebo. A higher incidence of acne and bronchitis was also observed in patients treated with RINVOQ 15 mg (1.3% and 3.9%, respectively) compared to placebo (0.3% and 2.7%, respectively).
• 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.
• Increased risk of death in people 50 years and older with at least 1 heart disease (cardiovascular) risk factor.
• Cancer and immune system problems. RINVOQ may increase your risk of certain cancers, including lymphoma, skin, and lung cancer, as these can happen. Current or past smokers are at higher risk.
• Increased risk of major cardiovascular events such as heart attack, stroke, or death in people 50 years and older with at least 1 heart disease (cardiovascular) risk factor, especially in current or past smokers.
• 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. This has happened more often in people 50 years and older with at least 1 heart disease (cardiovascular) risk factor.

Other serious side effects include tears in the stomach or intestines and changes in certain laboratory test results.

Ease of Use and Access

• Designed to help accommodate the physical limitations of people living with rheumatic diseases, the packaging for RINVOQ includes a bottle cap with a wide, easy-to-grip texture and an embedded tool that punctures the foil liner to simplify medication access. This packaging design was awarded the Arthritis Foundation Ease of Use Commendation. ⁴
• AbbVie continues to work closely with key stakeholders to support patient access to RINVOQ, 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 to qualifying patients. For more details, please visit AbbVie.com/myAbbVieAssist.

About Psoriatic Arthritis

Psoriatic arthritis (PsA) is a heterogeneous, systemic inflammatory disease with hallmark manifestations across multiple domains including joints and skin. ⁵ In PsA, the immune system causes inflammation that can lead to skin lesions associated with psoriasis, pain, fatigue and stiffness in the joints. ^5,6 PsA affects about 30% of people with psoriasis. ^7,8

About SELECT-PsA 1 ^1,2

SELECT-PsA 1 is a Phase 3, multicenter, randomized, double-blind, active comparator- and placebo-controlled study designed to evaluate the safety and efficacy of RINVOQ compared to placebo and adalimumab in adult patients with moderately to severely active psoriatic arthritis who have a history of intolerance or inadequate response to at least one non-biologic DMARD. Patients were randomized to RINVOQ 15 mg, RINVOQ 30 mg, adalimumab 40 mg every other week, or placebo followed by either RINVOQ 15 mg or RINVOQ 30 mg at week 24.

The primary endpoint was the percentage of subjects receiving RINVOQ 15 mg or 30 mg who achieved an ACR20 response after 12 weeks of treatment versus placebo. Key secondary endpoints included change from baseline in HAQ-DI at week 12, proportion of patients achieving, percentage of patients achieving a static Investigator Global Assessment (sIGA) of psoriasis of 0 or 1 and at least a 2-point improvement from baseline at week 16; percentage of patients achieving PASI 75 response at week 16; inhibition of radiographic progression at week 24 per the change from baseline in mTSS; the percentage of patients achieving MDA at week 24; percentage of participants with resolution of enthesitis at week 24; change from baseline in FACIT-F questionnaire at week 12; and percentage of patients with resolution of dactylitis at week 24. These are not all of the secondary endpoints. The long-term extension of the trial is ongoing. More information on this trial can be found at www.clinicaltrials.gov (NCT03104400).

About SELECT-PsA 2 ^1,3

SELECT-PsA 2 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of RINVOQ in adult patients with moderately to severely active psoriatic arthritis who have a history of intolerance or inadequate response to at least one biologic DMARD. Patients were randomized to RINVOQ 15 mg, RINVOQ 30 mg or placebo followed by either RINVOQ 15 mg or RINVOQ 30 mg at week 24.

The primary endpoint was the percentage of subjects achieving an ACR20 response after 12 weeks of treatment vs placebo. Key secondary endpoints included change from baseline in HAQ-DI at week 12, proportion of patients achieving ACR50 and ACR70 at week 12, proportion of patients achieving PASI 75 at week 16, as well as proportion of patients achieving MDA at week 24. These are not all of the secondary endpoints. The long-term extension of the trial is ongoing. More information on this trial can be found at www.clinicaltrials.gov (NCT03104374).

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. RINVOQ 15 mg is approved by the U.S. Food and Drug Administration (FDA) for adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers and adults with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers. RINVOQ 15 mg is also approved by the European Commission for adults with moderate to severe active rheumatoid arthritis, adults with active psoriatic arthritis and adults with active ankylosing spondylitis. RINVOQ is approved by the European Commission 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. ^9-16

RINVOQ U.S. Uses and Important Safety Information ¹

RINVOQ is a prescription medicine used 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
• 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 under 18 years of age.

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. 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.
• 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.
• 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.

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:

• 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 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

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:

• 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, bronchitis, nausea, cough, fever, and acne. 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 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 , 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.

References:

1. RINVOQ ^® (upadacitinib) [Package Insert]. North Chicago, Ill. : AbbVie Inc.
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3. Mease, P. J., et al. (2020). Upadacitinib for psoriatic arthritis refractory to biologics: Select-PSA 2. Annals of the Rheumatic Diseases , 80 (3), 312–320. https://doi.org/10.1136/annrheumdis-2020-218870 .
4. RINVOQ. Arthritis Foundation. Available at: https://www.arthritis.org/partnership/ease-of-use-products/rinvoq#:~:text=The%20Arthritis%20Foundation's%20Ease%20of,easy%20to%20use%20for%20everyone .
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6. Diseases & Conditions: Psoriatic Arthritis. 2019. American College of Rheumatology. Available at: https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Psoriatic-Arthritis . Accessed on: September 10, 2020 .
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8. Mease, P. J., Gladman, D. D., Papp, K. A., Khraishi, M. M., Thaci, D., Behrens, F., Alvarez, D. (2014) Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics. J Am Acad Dermatol, 69(5), 729-735.
9. Burmester G.R., et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Jun 23;391(10139):2503-2512. doi: 10.1016/S0140-6736(18)31115-2. Epub 2018 Jun 18.
10. 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. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635 . Accessed on August 17, 2020 .
11. 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. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649 . Accessed on August 17, 2020
12. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed: June 2021.
13. 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. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400 . Accessed on August 17, 2020 .
14. A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis (Heads Up). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03738397. Accessed: June 2021.
15. A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed: June 2021.
16. A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (SELECT-TAK). ClinicalTrials.gov. 2020. Available at https://clinicaltrials.gov/ct2/show/record/NCT04161898. Accessed: June 2021.

SOURCE AbbVie