JAMA Dermatology Publishes Data Showing RINVOQ® (upadacitinib) Achieved Superiority Versus DUPIXENT® (dupilumab) for Primary and All Ranked Secondary Endpoints in Phase 3b Head-to-Head Study in Adults with Atopic Dermatitis

NORTH CHICAGO, Ill., Aug. 4, 2021 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that JAMA Dermatology has published 24-week results from the Phase 3b Heads Up study evaluating the efficacy and safety of RINVOQ^® (upadacitinib, 30 mg, once daily) versus DUPIXENT^® (dupilumab, 300 mg, every other week) – both as monotherapy treatments – in adults with moderate to severe atopic dermatitis who were candidates for systemic therapy.

The publication expands upon previously announced topline results and showed upadacitinib (30 mg, once daily) achieved superiority compared to dupilumab for the primary endpoint, the proportion of patients with at least a 75 percent improvement in the Eczema Severity Index (EASI 75) at week 16.¹ Of those treated with upadacitinib, 71 percent achieved EASI 75 at week 16 compared to 61 percent of those treated with dupilumab.¹ Additionally, upadacitinib demonstrated statistically significant greater efficacy across all ranked secondary endpoints compared to dupilumab through week 16, including early reduction in itch and rates of skin clearance improvement.¹

"In this study, upadacitinib 30 mg demonstrated a more rapid onset of action compared to dupilumab, with patients experiencing a reduction in itch at one week and skin clearance improvements at two weeks. In addition, more upadacitinib-treated patients achieved high levels of skin clearance, such as EASI 90 and 100, by 16 weeks of treatment," said Andrew Blauvelt, MD, MBA, lead investigator for the Heads Up study and president of Oregon Medical Research Center in Portland, Oregon. "The results from this important comparative study will help inform how physicians work with their patients to set treatment goals for atopic dermatitis."

Results for select ranked secondary endpoints include:

• After one week of treatment, the upadacitinib 30 mg treatment group had a 31 percent reduction in itch (as measured by Worst Pruritus Numerical Rating Scale [NRS]) compared to 9 percent in the dupilumab group (p<0.001).¹
• After two weeks of treatment, 44 percent receiving upadacitinib achieved EASI 75 versus 18 percent receiving dupilumab (p<0.001). ¹
• At 16 weeks, 28 percent of people treated with upadacitinib achieved clear skin (EASI 100; p<0.001) and 61 percent achieved almost clear skin (EASI 90; p<0.001), compared to 8 percent and 39 percent, respectively, of those treated with dupilumab.¹

The safety profile of upadacitinib was consistent with what was observed in the Phase 3 pivotal studies, Measure Up 1, Measure Up 2 and AD Up.^1-3 Through week 16, the most common adverse events were acne for the upadacitinib group and conjunctivitis for the dupilumab group.¹ Serious adverse events occurred in 2.9 percent of those receiving upadacitinib and 1.2 percent of those receiving dupilumab.¹ Serious infections were reported infrequently in both treatment groups (1.1 percent in those who received upadacitinib and 0.6 percent in those who received dupilumab).¹ One treatment-emergent death due to bronchopneumonia associated with influenza A occurred in a patient who received upadacitinib.¹ No malignancies were reported in the upadacitinib group; one non-melanoma skin cancer was reported in the dupilumab group.¹ No major adverse cardiac events or venous thromboembolic events were reported in either treatment group.¹

About Heads Up¹
Heads Up is a Phase 3b multicenter, randomized, double-blind, double-dummy, active comparator-controlled study in adults with moderate to severe atopic dermatitis. Patients were randomized to receive upadacitinib (30 mg, once daily, orally administered) or dupilumab (300 mg, every other week, subcutaneous injection) for 24 weeks. Patients who received dupilumab received an initial dose of 600 mg at the baseline visit followed by 300 mg every other week. All patients received placebo of the other treatment as part of the Heads Up double-dummy study design.

The primary endpoint was the proportion of patients achieving EASI 75 at week 16. Ranked secondary endpoints were percent change from baseline in Worst Pruritus NRS (weekly average) at weeks 1, 4 and 16; proportion of patients achieving EASI 100 and EASI 90 at week 16; proportion of patients achieving EASI 75 at week 2; and Worst Pruritus NRS (weekly average) improvement ≥4 at week 16. Additional endpoints at week 24 included EASI 75, EASI 90, EASI 100 and improvement from baseline Worst Pruritus NRS (weekly average). More information on this trial can be found at www.clinicaltrials.gov (NCT03738397).

About Upadacitinib (RINVOQ^®)⁴
Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2. RINVOQ 15 mg is approved by the U.S. Food and Drug Administration (FDA) for adults with moderately to severely active rheumatoid arthritis. RINVOQ 15 mg also is approved by the European Medicines Agency (EMA) for adults with moderate to severe active rheumatoid arthritis, adults with active psoriatic arthritis (PsA) and adults with active ankylosing spondylitis (AS).

Use of RINVOQ in moderate to severe atopic dermatitis is not approved and its safety and efficacy are under evaluation by the U.S. FDA and the EMA. In June 2021, the EMA's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the approval of RINVOQ for the treatment of 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.^5-12

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.

Please see the Full Prescribing Information, including the Medication Guide, for RINVOQ. 

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'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 Statement
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. Blauvelt, A., et. al. A Phase 3 Trial of Upadacitinib Versus Dupilumab in Atopic Dermatitis. JAMA Dermatology doi: 10.1001/jamadermatol.2021.3023
2. Guttman-Yassky E., et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate, double-blind, randomized controlled phase 3 studies. Lancet. doi:10.1016/s0140-6736(21)00588-2.
3. Reich K., et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomized, double-blind, placebo-controlled phase 3 trial. Lancet. doi:10.1016/s0140-6736(21)00589-4.
4. RINVOQ^® (upadacitinib) [Package Insert]. North Chicago, Ill.: AbbVie Inc.
5. Pipeline – Our Science | AbbVie. AbbVie. 2019. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on August 17, 2020.
6. 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.
7. 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
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 August 17, 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 August 17, 2020.
10. 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 on August 17, 2020.
11. A Study to Evaluate Upadacitinib in Adolescent and Adult Subjects With Moderate to Severe Atopic Dermatitis. ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/record/NCT03607422. Accessed on August 17, 2020.
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. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on August 17, 2020.

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