NORTH CHICAGO, Ill., Aug. 16, 2019 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has approved RINVOQ™ (upadacitinib), a 15 mg, once-daily oral Janus kinase (JAK) inhibitor, for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate (MTX-IR).1 RINVOQ is expected to be available in the U.S. in late August 2019.

The FDA approval of RINVOQ is supported by data from the SELECT program, one of the largest registrational Phase 3 programs in RA with approximately 4,400 patients evaluated across all treatment arms in five studies.2-6 The studies include assessments of efficacy, safety and tolerability across a variety of RA patients, including those who failed or were intolerant to biologic disease-modifying anti-rheumatic drugs and who were naïve or inadequate responders to methotrexate. RINVOQ is not indicated for methotrexate-naïve patients.

"Despite the availability of multiple treatment options with varying mechanisms of action, many patients still do not achieve clinical remission or low disease activity—the primary treatment goals for rheumatoid arthritis," said Roy M. Fleischmann, M.D., primary investigator for SELECT-COMPARE and clinical professor at the University of Texas Southwestern Medical Center at Dallas. "With this FDA approval, RINVOQ has the potential to help additional people living with RA achieve remission who have not yet reached this goal."

Across the SELECT Phase 3 studies, RINVOQ met all primary and ranked secondary endpoints. The primary endpoints include:

In SELECT-EARLY, 52 percent of MTX-naïve patients treated with RINVOQ 15 mg achieved ACR50 vs 28 percent treated with MTX at week 12 1

In SELECT-MONOTHERAPY, 68 percent of MTX-IR patients treated with RINVOQ 15 mg achieved ACR20 vs 41 percent treated with continued MTX at week 14 1

In SELECT-COMPARE, 71 percent of MTX-IR patients treated with RINVOQ 15 mg plus MTX achieved ACR20 vs 36 percent treated with placebo plus MTX at week 12 1

In SELECT-NEXT, 64 percent of csDMARD-IR patients treated with RINVOQ 15 mg plus csDMARDs achieved ACR20 vs 36 percent treated with placebo plus csDMARDs at week 12 1

In SELECT-BEYOND, 65 percent of biologic-IR patients treated with RINVOQ 15 mg plus csDMARDs achieved ACR20 vs 28 percent treated with placebo plus csDMARDs at week 121

"The discovery and development of RINVOQ is indicative of AbbVie's long-standing commitment to advancing the science for people living with immune-mediated conditions," said Michael Severino, M.D., vice chairman and president, AbbVie. "Today's FDA approval marks an important milestone in our pursuit to deliver innovative medicines that advance care for people living with rheumatoid arthritis."

Clinical Remission

Patients taking RINVOQ achieved clinical remission, a state characterized by almost no disease activity and symptoms, even without methotrexate.2-3,6 Approximately 30 percent of patients treated with RINVOQ achieved clinical remission (as assessed by DAS28-CRP<2.6) at week 12 in SELECT-COMPARE and week 14 in SELECT-MONOTHERAPY compared to six percent with placebo plus methotrexate and eight percent with methotrexate, respectively.1 In SELECT-EARLY, 36 percent of patients treated with RINVOQ achieved clinical remission (as assessed by DAS28-CRP<2.6) at week 12 compared to 14 percent with methotrexate.1

Durable remission rates were observed up to week 26. Forty-eight percent of patients treated with RINVOQ alone in SELECT-EARLY and 41 percent of patients treated with RINVOQ plus methotrexate in SELECT-COMPARE achieved clinical remission at weeks 24 and 26, compared to nine percent with placebo plus methotrexate and 18 percent with methotrexate, respectively.1 Analysis at weeks 24 and 26 were not controlled for multiple comparisons.3,10

Radiographic Inhibition

RINVOQ significantly inhibited radiographic progression as measured by the change in modified total Sharp score (mTSS) from baseline compared to methotrexate in SELECT-EARLY (0.14 vs 0.67) and RINVOQ plus methotrexate compared to placebo plus methotrexate in SELECT-COMPARE (0.15 vs 0.78) through weeks 24 and 26, respectively.1

Safety

The most common side effects associated with RINVOQ include upper respiratory tract infections (common cold, sinus infections), nausea, cough and pyrexia.1 Patients treated with RINVOQ are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include tuberculosis (TB), invasive fungal, bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.1 Lymphoma and other malignancies have been observed in RINVOQ-treated patients.1 Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions.1 Patients treated with RINVOQ also may be at risk for other serious adverse reactions, including gastrointestinal perforations, neutropenia, lymphopenia, anemia, lipid elevations, liver enzyme elevations, and embryo-fetal toxicity.1

Ease of Use and Access

Designed to help accommodate the physical limitations of people living with RA, 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.

"Rheumatoid arthritis can have a debilitating impact on the lives of those with the chronic disease, including making it difficult to perform everyday tasks," said Cindy McDaniel, senior vice president, consumer health, Arthritis Foundation. "The Arthritis Foundation is committed to recognizing innovation that can help patients living with rheumatoid arthritis and we are proud to recognize AbbVie with our Ease of Use Commendation for the packaging design of RINVOQ."

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.

About Rheumatoid Arthritis

Affecting 1.3 million Americans, rheumatoid arthritis is a complex, systemic autoimmune disease that occurs when the immune system mistakenly attacks joints, creating inflammation that causes the tissue inside of joints to thicken, damaging the bones and associated connective tissue.11-12 Pain, fatigue and stiffness are among the signs and symptoms of RA that can have an impact on daily living.13 If not properly treated, RA can lead to permanent, debilitating bone and cartilage damage.

The full U.S. prescribing information, including Medication Guide, for RINVOQ can be found on rxabbvie.com.

About RINVOQ1

RINVOQ is an oral, small molecule JAK inhibitor being studied for moderately to severely active rheumatoid arthritis and other immune-mediated diseases. RINVOQ is under review by the European Medicines Agency (EMA), as well as regulatory authorities in Canada and Japan, for the treatment of adult patients with moderately to severely active RA.

RINVOQ U.S. Use and Important Safety Information1

RINVOQ is a prescription medicine used to treat adults with moderate to severe rheumatoid arthritis in whom methotrexate 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 is a medicine that can lower the ability of your immune system to fight infections. You should not start taking RINVOQ if you have any kind of infection unless your healthcare provider (HCP) tells you it is okay.

Serious infections have happened in some people 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 HCP should test you for TB before starting RINVOQ and check you closely for signs and symptoms of TB during treatment with RINVOQ. You may be at higher risk of developing shingles (herpes zoster).

Your HCP should test you for TB before starting RINVOQ and check you closely for signs and symptoms of TB during treatment with RINVOQ. You may be at higher risk of developing shingles (herpes zoster). Lymphoma and other cancers, including skin cancers, can happen in people taking RINVOQ.

Blood clots in the veins of the legs or lungs and arteries are possible in some people taking RINVOQ. This may be life-threatening and cause death.

Tears in the stomach or intestines and changes in certain laboratory tests can happen. 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: 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.

Have had any type of cancer, hepatitis B or C, shingles (herpes zoster), or 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 that increase your risk of getting certain kinds of fungal infections, such as the Ohio and Mississippi River valleys and the Southwest. If you are unsure if you've been to these areas, ask your HCP.

and Mississippi River valleys and the Southwest. 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

Ask your HCP or pharmacist if you are not sure if you are taking any of these medicines.

What should I 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.

Have any signs or symptoms of blood clots during treatment with RINVOQ, including: Swelling Pain or tenderness in the leg Sudden unexplained chest pain Shortness of breath

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), nausea, cough, and fever. These are not all the possible side effects of 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.

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.

About AbbVie

AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. 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, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. 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 2018 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. 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. 2 Smolen J. et al. Upadacitinib as monotherapy: a phase 3 randomized controlled double-blind study in patients with active rheumatoid arthritis and inadequate response to methotrexate. Presented at 2018 European League Against Rheumatism (EULAR) Annual Meeting; June 13-16, 2018; Amsterdam, Netherlands. 3 Fleischmann R, et al. A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. Presented at 2018 ACR/ARHP Annual Meeting; October 19-24, 2018; Chicago, Ill 4 Burmester GR, 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 randomized, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10139):2503-2512. doi: 10.1016/S0140-6736(18)31115-2. Epub 2018 Jun 18. 5 Genovese MC, et al. Upadacitinib (ABT-494) in patients with active rheumatoid arthritis and inadequate response or intolerance to biological DMARDs: a phase 3 randomized, placebo-controlled, double-blind study of a selective JAK1 inhibitor. Presented at 2018 European League Against Rheumatism (EULAR) Annual Meeting; June 13-16, 2018; Amsterdam, Netherlands. 6 van Vollenhoven, et al. A phase 3, randomized, controlled trial comparing upadacitinib monotherapy to MTX monotherapy in MTX-naïve patients with active rheumatoid arthritis. Presented at 2018 ACR/ARHP Annual Meeting; October 19-24, 2018; Chicago, Ill. 7 AbbVie. Data on File. ABVRRTI68885 8 Chowdhury B. Center for Drug Evaluation and Research Summary Review of Regulatory Action Application Number: 203215Orig1s000. November 6, 2012. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203214Orig1s000SumR.pdf 9 Okada, S. Clinical Review of Complete Response. BLA 125276/0/64. CDER/ODEII/DAARP. December 11, 2009. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/125276s000MedR.pdf 10 AbbVie. Data on File. ABVRRTI68564 11 Arthritis Foundation. What is Rheumatoid Arthritis. Available at: https://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/what-is-rheumatoid-arthritis.php. Accessed on July 9, 2019 12 Hunter T, et al. Rheumatology International. Prevalence of rheumatoid arthritis in the United States adult population in healthcare claims databases, 2004–2014. April 2017. 13 American College of Rheumatology. Rheumatoid Arthritis. Available at: https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Rheumatoid-Arthritis. Accessed on June 7, 2019.

SOURCE AbbVie