Third Pivotal Phase 3 Study Shows RINVOQ™ (upadacitinib) Plus Topical Corticosteroids Improves Skin and Itch Symptoms in Atopic Dermatitis Patients

NORTH CHICAGO, Ill., July 28, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced upadacitinib (15 mg and 30 mg, once daily) plus topical corticosteroids (TCS) met the co-primary endpoints and all secondary endpoints in AD Up, the third pivotal Phase 3 study of RINVOQ in atopic dermatitis.¹ AD Up evaluated the efficacy and safety of both doses of upadacitinib therapy versus placebo in adults and adolescents with moderate to severe atopic dermatitis; all treatment groups, including placebo, received concomitant TCS.¹ The co-primary endpoints were at least a 75 percent improvement in the Eczema Area Severity Index (EASI 75) from baseline and a validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 (clear or almost clear) at week 16.¹

Significantly more patients receiving either dose of upadacitinib plus TCS showed improvement in skin clearance compared to placebo plus TCS at week 16.¹ In the study, 65/77 percent of patients receiving upadacitinib 15/30 mg plus TCS achieved EASI 75, respectively, versus 26 percent receiving placebo plus TCS (p<0.001).¹ Of patients treated with upadacitinib 15/30 mg plus TCS, 40/59 percent achieved vIGA-AD 0/1, respectively, versus 11 percent of patients receiving placebo plus TCS (p<0.001).¹

"These data build on the positive results from our previous studies in atopic dermatitis, now with additional perspective on the efficacy of RINVOQ used with a mainstay treatment for people living with the disease – topical steroids," said Tom Hudson, M.D., senior vice president of R&D and chief scientific officer, AbbVie. "With our deep heritage in serious skin diseases, we look forward to advancing research with RINVOQ as part of our ultimate goal to address unmet needs and improve care for people living with the relentless itch and skin symptoms of atopic dermatitis."

Additionally, more patients treated with upadacitinib plus TCS experienced a clinically meaningful reduction in itch, defined as improvement in Worst Pruritus Numerical Rating Scale (NRS)≥4, compared to patients treated with placebo plus TCS.¹ At week 16, 52/64 percent of patients receiving upadacitinib 15/30 mg plus TCS achieved this endpoint compared to 15 percent of patients receiving placebo plus TCS (p<0.001).¹

In a pre-specified additional analysis, treatment with either dose of upadacitinib also led to a higher mean number of topical corticosteroid-free days (TCS-free days) up to week 16 versus placebo.¹ A TCS-free day is defined by a response of EASI 75 or greater without the use of TCS.¹ Patients treated with upadacitinib 15/30 mg had a mean of 34/47 TCS-free days while maintaining EASI 75, respectively, compared with a mean of 8 days for those treated with placebo plus TCS (nominal p<0.001).¹

"These results are encouraging, including the analysis showing some patients in the upadacitinib treatment groups were able to control their skin symptoms without topical corticosteroids," said Kristian Reich, M.D., professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg Eppendorf, and Skinflammation Center, Hamburg, Germany and principal investigator. "Many of the current treatment options rely on patients to self-manage their condition, often with multiple applications of topicals. Patients could benefit from more therapeutic options that can help control symptoms without the constant need for concomitant topicals, as they strive for relief from this life-long, chronic disease."

Atopic dermatitis is a chronic, relapsing inflammatory condition characterized by a cycle of intense itching and scratching leading to cracked, scaly, oozing skin.^12,13 It affects up to an estimated 25 percent of adolescents and 10 percent of adults at some point in their lifetime.¹³ Between 20 and 46 percent of adults with atopic dermatitis have moderate to severe disease.¹⁴ The range of symptoms pose significant physical, psychological and economic burden on individuals impacted by the disease.^13,15

Safety results were consistent with the two previously reported Phase 3 studies in atopic dermatitis, with no new safety risks observed during the 16-week placebo-controlled period.^1-3 Serious adverse events (SAEs) occurred in 2.3 percent of patients in the upadacitinib 15 mg plus TCS group and 1.3 percent of patients in the upadacitinib 30 mg plus TCS group compared to 3.0 percent of patients in the placebo plus TCS group.¹ The most common AEs for the upadacitinib groups were nasopharyngitis, acne and upper respiratory tract infection.¹ Acne was observed at higher rates in the 15 mg and 30 mg upadacitinib plus TCS groups (10.0 percent and 13.8 percent, respectively) versus placebo plus TCS group (2.0 percent); all events were mild or moderate in severity and none led to treatment discontinuation.¹ Eczema herpeticum was observed in 1.0 percent of patients on upadacitinib 15 mg plus TCS and 1.3 percent of patients on upadacitinib 30 mg plus TCS; none were reported in patients on placebo plus TCS.¹ Serious infections were reported infrequently (1.0 percent in the upadacitinib 15 mg plus TCS group, 1.0 percent in the placebo plus TCS group; none were reported in the upadacitinib 30 mg plus TCS group).¹ One event of arterial thrombosis occurred in a patient on placebo plus TCS.¹ No deaths, major adverse cardiac events or venous thromboembolic events were reported in any of the treatment groups.¹

Full results from the AD Up study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal. Use of RINVOQ in atopic dermatitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

About AD Up^1,11

AD Up, together with Measure Up 1 and Measure Up 2 (top-line results announced in June and July 2020), make up AbbVie's Phase 3 pivotal trial program evaluating RINVOQ for the treatment of individuals with moderate to severe atopic dermatitis (ages 12 and older) who are candidates for systemic treatment.

AD Up is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study. Patients were randomized to upadacitinib 15 mg, upadacitinib 30 mg or placebo, all in combination with TCS. Patients receiving placebo plus TCS were switched to either upadacitinib 15 mg or upadacitinib 30 mg plus TCS at week 16.

The co-primary endpoints were the percentage of patients achieving EASI 75 and a vIGA-AD of 0/1 after 16 weeks of treatment. Secondary endpoints included improvement in Worst Pruritus NRS≥4, EASI 90, percent change in Worst Pruritus NRS, percent change in EASI at week 16. The trial is ongoing, and the long-term extension period remains blinded to investigators and patients, to evaluate the long-term safety, tolerability and efficacy of the two once daily doses (15 mg and 30 mg) of upadacitinib plus TCS in patients who have completed the placebo-controlled period. More information on this trial can be found at www.clinicaltrials.gov (NCT03568318).

About RINVOQ (upadacitinib)

Discovered and developed by AbbVie scientists, RINVOQ is an oral, once-daily, selective and reversible JAK inhibitor studied in several immune-mediated inflammatory diseases.^1,4-11 It was engineered to have greater inhibitory potency for JAK1 versus JAK2, JAK3 and TYK2.¹⁶ In August 2019, RINVOQ received U.S. Food and Drug Administration approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. In December 2019, RINVOQ also received approval by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. The approved dose for RINVOQ in rheumatoid arthritis is 15 mg. Phase 3 trials of RINVOQ in atopic dermatitis, rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, ulcerative colitis and giant cell arteritis are ongoing.^5-11 Use of RINVOQ in atopic dermatitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

Important Safety Information about RINVOQ™ (upadacitinib)

RINVOQ U.S. Use and Important Safety Information
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).
• 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.
• 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
• Sudden unexplained chest pain
• Pain or tenderness in the leg
• 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 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 Dermatology

For more than a decade, AbbVie has worked to uncover new solutions and improve care for people with serious skin diseases, including psoriasis, psoriatic arthritis, hidradenitis suppurativa and atopic dermatitis. With a broad clinical trial program, we continue to actively research and adapt to the evolving needs of the dermatology community and advance our pipeline to help people achieve their treatment goals and live beyond their skin disease. For more information on AbbVie in dermatology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/dermatology.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, 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 2019 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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5. 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.
6. 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 July 22, 2020.
7. 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 July 22, 2020.
8. 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 July 22, 2020.
9. A Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis (SELECT Axis 1). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/study/NCT03178487. Accessed on July 22, 2020.
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11. A Study to Evaluate Upadacitinib in Combination With Topical Corticosteroids in Adolescent and Adult Participants With Moderate to Severe Atopic Dermatitis (AD Up). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/study/NCT03568318. Accessed July 22, 2020.
12. Nutten S. Atopic Dermatitis: Global Epidemiology and Risk Factors. Ann Nutr Metab 2015;66(suppl 1):8–16.
13. Weidinger S, et al. Atopic dermatitis. Nat Rev Dis Primers 4, 1 (2018). https://doi.org/10.1038/s41572-018-0001-z.
14. Shrestha S, et al. Burden of Atopic Dermatitis in the United States: Analysis of Healthcare Claims Data in the Commercial, Medicare, and Medi-Cal Databases. Adv Ther. 2017;34(8):1989–2006.
15. EFA. Atopic Eczema: Itching for Life Report. 2018. Available at: https://www.efanet.org/images/2018/EN_-_Itching_for_life_Quality_of_Life_and_costs_for_people_with_severe_atopic_eczema_in_Europe_.pdf. Accessed on July 16, 2020.
16. Cohen S, et al. Safety profile of upadacitinib in Rheumatoid Arthritis: Integrated analysis from the SELECT Phase 3 Clinical Program. EULAR 2019; THU0167. 

SOURCE AbbVie

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