AbbVie Presents New Analyses Evaluating RINVOQ® in Atopic Dermatitis Across Patient Characteristics and Body Regions at EADV Virtual Congress

ABBVie (NYSE: ABBV) today announced new analyses from the Phase 3 RINVOQ ® (upadacitinib) atopic dermatitis clinical trial program to be presented at the 30th European Academy of Dermatology and Venereology (EADV) Virtual Congress. One analysis showed a greater proportion of patients treated with RINVOQ (15 mg or 30 mg; once daily) with or without topical corticosteroids achieved 75 percent improvement in the Eczema Area Severity Index (EASI 75) at week 16 compared to placebo, regardless of age, sex, race, weight, disease severity and previous exposure to systemic therapy. 1 An additional analysis showed more patients treated with RINVOQ 30 mg achieved EASI 75 at week 16 compared to dupilumab when measured in four body regions. 2

"These data further highlight RINVOQ's potential to help alleviate the itch and rash in moderate to severe atopic dermatitis, offering additional support of its efficacy across various patient characteristics and areas of the body," said Thomas Hudson , M.D., senior vice president, research and development, chief scientific officer, AbbVie. "Advancing research and fostering innovation remain at the heart of our efforts to help transform care for atopic dermatitis patients, many of whom still suffer from the unrelenting symptoms of the disease despite available treatment options."

P0183: Efficacy of Upadacitinib for Moderate-to-Severe Atopic Dermatitis: Stratified Analysis from Three Phase 3 Trials by Key Baseline Characteristics: Study Highlights
In this study, investigators presented results evaluating whether RINVOQ efficacy observed in the global Phase 3 clinical trials (Measure Up 1, Measure Up 2 and AD Up) differed based on age, weight, sex, disease severity, race/ethnicity and previous treatment history. ¹ The analysis observed that for the 15 mg and 30 mg treatment groups, the percentage of patients achieving the primary endpoint of EASI 75 at week 16 across the subgroups was consistent with that observed in the overall study population. ¹ More than half of all patients for all subgroups (more than 51 percent, nominal p 1 A numerically greater proportion of patients receiving RINVOQ 30 mg across all subgroups (more than 61 percent, nominal p 1

"Atopic dermatitis is a chronic, relapsing, heterogenous disease that manifests with a wide variety of clinical symptoms and signs that can vary by patient. While there are treatments available, many patients still experience the signs and symptoms of the disease and continue to seek additional options," said Jacob P. Thyssen , M.D., Ph.D., Department of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen and lead author of the stratified analysis for the three Phase 3 pivotal global trials and the additional analysis of the Heads Up study. "The outcomes of these additional analyses from the Phase 3 studies and head-to-head data help to further enhance our knowledge of the breadth, depth and speed of response with RINVOQ in patients with moderate to severe atopic dermatitis."

FC01.03: Efficacy and Safety of Upadacitinib vs Dupilumab Treatment for Moderate to Severe Atopic Dermatitis in Four Body Regions - Analysis from the Heads Up Study
In this oral presentation, investigators shared a new analysis from Heads Up, a Phase 3b head-to-head study, showing more patients treated with RINVOQ 30 mg, once daily, achieved EASI 75 compared to dupilumab 300 mg, every other week, in four body regions as early as week 1 and maintained through week 16. ² The four body regions evaluated included head and neck, trunk, upper limbs and lower limbs. ²

In the Heads Up analysis, safety results were consistent with those observed in the global Phase 2b and Phase 3 pivotal studies. ² No new safety risks were observed compared with the known safety profile of RINVOQ. ² The most common adverse event (AE) reported with RINVOQ was acne (15.8 percent) and with dupilumab was conjunctivitis (9.4 percent). ² There was a higher rate of serious AEs (2.9 percent versus 1.2 percent) and serious infections (1.1 percent versus 0.6 percent) in the RINVOQ group compared with the dupilumab group. ^2,6

Late-breaking Presentation

In a late-breaking presentation, Efficacy and Safety of Switching from Dupilumab to Upadacitinib in Moderate-to-Severe Atopic Dermatitis: Results from an Open-Label Extension Trial (D1T01.3B) , interim results will be shared from an open-label extension (OLE) that followed the Heads Up study, evaluating the efficacy and safety of RINVOQ 30 mg in patients who were initially randomized to either RINVOQ 30 mg or dupilumab 300 mg, completed the 24-week head-to-head Phase 3b Heads Up study and were candidates for long-term RINVOQ therapy according to the study investigator. ³ A total of 245 patients initially randomized to dupilumab and 239 patients initially randomized to RINVOQ who completed Heads Up were subsequently enrolled in the OLE. ³ At 16 weeks after the switch to RINVOQ (at week 40), treatment with RINVOQ resulted in high rates of skin clearance and itch improvement. ³

Among patients who did not achieve EASI 75 on dupilumab at week 24 in the Heads Up study (n=32), 88 percent, 69 percent and 22 percent of those patients achieved EASI 75, EASI 90 and EASI 100, respectively, after 16 weeks of RINVOQ 30 mg treatment. ³ The safety profile of RINVOQ 30 mg with continued treatment through 40 weeks and in subjects switching from dupilumab to RINVOQ was consistent with the safety profile of RINVOQ observed in the Phase 3 pivotal atopic dermatitis studies, Measure Up 1, Measure Up 2 and AD Up. ³ The rates of serious adverse events and serious infection in RINVOQ-treated patients was 6.6 and 2.5 events per 100 patient-years (PY), respectively (N=239; PY=242.3). ³ There were no reports of malignancy, gastrointestinal perforation, major adverse cardiac events and thromboembolic events through 40 weeks of treatment. ³ There was one death due to bone tuberculosis in a 69 year-old female. ³ No new safety risks were observed. ³

About Measure Up 1 and Measure Up 2 ⁴

Measure Up 1 and Measure Up 2 are Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled studies designed to evaluate the safety and efficacy of RINVOQ in adult and adolescent (12 years or older) patients with moderate to severe atopic dermatitis who are candidates for systemic treatment. Patients were randomized to RINVOQ 15 mg, RINVOQ 30 mg or placebo, followed by either RINVOQ 15 mg or RINVOQ 30 mg at week 16. The co-primary endpoints were the percentage of patients achieving EASI 75 and a validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 after 16 weeks of treatment.

About AD Up ⁵

AD Up is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the safety and efficacy of RINVOQ in adult and adolescent (12 years or older) patients with moderate to severe atopic dermatitis who are candidates for systemic treatment. Patients were randomized to RINVOQ 15 mg, RINVOQ 30 mg or placebo, all in combination with topical corticosteroids (TCS). Patients receiving placebo plus TCS were switched to either RINVOQ 15 mg or RINVOQ 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.

About Heads Up ⁶

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 RINVOQ (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 arm's administration as part of the Heads Up double-dummy study design. The primary endpoint was the proportion of patients achieving EASI 75 at week 16.

About RINVOQ ^® (upadacitinib)  

Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. ^7-16 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. ⁷ RINVOQ is approved by the European Commission for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate to severe atopic dermatitis. RINVOQ 15 mg is 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. 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. ^8-16

EU Indications and Important Safety Information About RINVOQ ^® (upadacitinib) ⁷

Rheumatoid arthritis
RINVOQ is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate.

Psoriatic arthritis
RINVOQ is indicated for the treatment of active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs. RINVOQ may be used as monotherapy or in combination with methotrexate.

Ankylosing spondylitis
RINVOQ is indicated for the treatment of active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy.

Atopic dermatitis
RINVOQ is indicated for the treatment of moderate to severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy.

Contraindications
RINVOQ is contraindicated in patients hypersensitive to the active substance or to any of the excipients, in patients with active tuberculosis (TB) or active serious infections, in patients with severe hepatic impairment, and during pregnancy.

Special warnings and precautions for use
Immunosuppressive medicinal products
Use in combination with other potent immunosuppressants is not recommended.

Serious infections
Serious and sometimes fatal infections have been reported in patients receiving upadacitinib. The most frequent serious infections reported included pneumonia and cellulitis. Cases of bacterial meningitis have been reported. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis have been reported with upadacitinib. As there is a higher incidence of infections in patients ≥65 years of age, caution should be used when treating this population.

Viral reactivation
Viral reactivation, including cases of herpes zoster, was reported in clinical studies. The risk of herpes zoster appears to be higher in Japanese patients treated with upadacitinib.

Vaccinations
The use of live, attenuated vaccines during or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunizations, including prophylactic zoster vaccinations, prior to initiating upadacitinib, in agreement with current immunization guidelines.

Malignancy
The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Malignancies, including nonmelanoma skin cancer (NMSC), have been reported in patients treated with upadacitinib. Consider the risks and benefits of upadacitinib treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated NMSC or when considering continuing upadacitinib therapy in patients who develop a malignancy.

Hematological abnormalities
Treatment should not be initiated, or should be temporarily interrupted, in patients with hematological abnormalities observed during routine patient management.

Cardiovascular risk
RA patients have an increased risk for cardiovascular disorders. Patients treated with upadacitinib should have risk factors (e.g., hypertension, hyperlipidemia) managed as part of usual standard of care.

Lipids
Upadacitinib treatment was associated with dose-dependent increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol.

Hepatic transaminase elevations
Treatment with upadacitinib was associated with an increased incidence of liver enzyme elevation compared to placebo.

Venous thromboembolisms
Events of deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors, including upadacitinib. Upadacitinib should be used with caution in patients at high risk for DVT/PE .

Adverse reactions

The most commonly reported adverse reactions in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis clinical trials (≥2% of patients in at least one of the indications) with upadacitinib 15 mg were upper respiratory tract infections, blood creatine phosphokinase (CPK) increased, alanine transaminase (ALT) increased, bronchitis, nausea, cough, aspartate transaminase (AST) increased, and hypercholesterolemia.

The most commonly reported adverse reactions in atopic dermatitis trials (≥2% of patients) with upadacitinib 15 mg or 30 mg were upper respiratory tract infection, acne, herpes simplex, headache, CPK increased, cough, folliculitis, abdominal pain, nausea, neutropenia, pyrexia, and influenza.

The most common serious adverse reactions were serious infections.

The safety profile of upadacitinib with long–term treatment was generally similar to the safety profile during the placebo–controlled period across indications.

Overall, the safety profile observed in patients with psoriatic arthritis or active ankylosing spondylitis treated with upadacitinib 15 mg was consistent with the safety profile observed in patients with RA.

In atopic dermatitis, dose-dependent increased risks of infection and herpes zoster were observed with upadacitinib. Based on limited data, there was a higher rate of overall adverse reactions with the upadacitinib 30 mg dose compared to the 15 mg dose in patients aged 65 years and older. The safety profile for upadacitinib 15 mg in adolescents was similar to that in adults. The safety and efficacy of the 30 mg dose in adolescents are still being investigated. Dose-dependent changes in ALT increased and/or AST increased (≥ 3 x ULN), lipid parameters, CPK values (> 5 x ULN), and neutropenia (ANC 9 cells/L) associated with upadacitinib treatment were similar to what was observed in the rheumatologic disease clinical studies.

This is not a complete summary of all safety information.

Please see the RINVOQ full SmPC for complete prescribing information at https://www.EMA.europa.eu.

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. Thyssen, JP, et al. Efficacy of Upadacitinib for Moderate-to-Severe Atopic Dermatitis: Stratified Analysis from Three Phase 3 Trials by Key Baseline Characteristics. European Academy of Dermatology and Venerology Congress. 2021. P0183.
2. Thyssen, JP, et al. Efficacy and Safety of Upadacitinib vs Dupilumab Treatment for Moderate to Severe Atopic Dermatitis in Four Body Regions - Analysis from the Heads Up Study. European Academy of Dermatology and Venerology Congress. 2021. FC01.03.
3. Blauvelt, A, et al. Efficacy and Safety of Switching from Dupilumab to Upadacitinib in Moderate-to-Severe Atopic Dermatitis: Results from an Open-Label Extension Trial. European Academy of Dermatology and Venerology Congress. 2021. D1T01.3B.
4. 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, randomised controlled phase 3 trials. Lancet. 2021; 397(10290): 2151-2168. doi:10.1016/S0140-6736(21)00588-2.
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