AbbVie to Present New Analyses from Pivotal Phase 3 Studies for RINVOQ in Atopic Dermatitis

- Late-breaking data analyses to be presented by ABBVie (NYSE: ABBV) at the 29 th European Academy of Dermatology and Venereology (EADV) Virtual Congress show that significantly more atopic dermatitis patients treated with upadacitinib (15 mg or 30 mg; once daily) monotherapy achieved improvement in additional measures of skin clearance and reduction in itch compared to placebo. 1 These data are from the Phase 3 Measure Up 1 and Measure Up 2 studies, which support the recent applications to the U.S. Food and Drug Administration and European Medicines Agency, seeking approval for RINVOQ in adult and adolescent patients with moderate to severe atopic dermatitis.

In both of the Measure Up 1 and 2 studies, significantly more patients treated with either dose of upadacitinib achieved at least a 90 percent improvement in the Eczema Area Severity Index (EASI 90) compared to patients treated with placebo at week 16 (53/66 percent of patients receiving upadacitinib 15/30 mg versus 8 percent receiving placebo in Measure Up 1; 42/58 percent of patients receiving upadacitinib 15/30 mg versus 5 percent receiving placebo in Measure Up 2) [p 1 Additionally, for both doses of upadacitinib, the proportion of patients achieving a clinically meaningful itch reduction was significantly higher than placebo at week 4 and maintained through week 16. ¹ A clinically meaningful itch reduction was defined as improvement in Worst Pruritus Numerical Rating Scale (NRS)≥4. ¹

"I'm encouraged to see results showing a high proportion of patients treated with upadacitinib achieved EASI 90, or almost clear skin, and significant reduction in their itch," said lead investigator Emma Guttman-Yassky , M.D., Ph.D., professor of dermatology and immunology, director of the center for excellence in eczema and laboratory for inflammatory skin diseases and the incoming chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai in New York .* "The speed and degree of response with upadacitinib are meaningful to patients, many of whom suffer from substantial burden of disease that can interfere with daily life."

Earlier this year, AbbVie announced top-line data from Measure Up 1 and Measure Up 2 showing upadacitinib (15 mg or 30 mg) met the co-primary endpoints of EASI 75 and a validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 (clear or almost clear) at week 16. ¹

At EADV, AbbVie will also present new analyses showing significantly more patients reported improvements in quality of life as measured by a Dermatology Life Quality Index (DLQI) score of 0/1 after 16 weeks of treatment with either dose of upadacitinib, compared to those on placebo. ¹ DLQI is a measure of a patient's health-related quality of life, ranging from 0 to 30, with a score of 0 or 1 indicating the disease no longer had an impact on their quality of life. ⁵

These and additional data are being presented as part of the "Late Breaking News" session (Abstract #D3T03.4B) on October 31 from 4:00-4:15 p.m. CET / 10:00-10:15 a.m. CT , during the EADV Virtual Congress.

No new safety risks were identified compared to those from previous studies with RINVOQ. ^1-4 As previously reported, during the 16-week placebo-controlled period in Measure Up 1, serious adverse events (SAEs) were reported in 2.1 percent of patients receiving upadacitinib 15 mg and 2.8 percent of patients receiving either upadacitinib 30 mg or placebo. ¹ In Measure Up 2, SAEs were reported in 1.8 percent of patients receiving upadacitinib 15 mg, 2.5 percent of patients receiving upadacitinib 30 mg and 2.9 percent of patients receiving placebo. ¹ Serious infections were reported infrequently in both Measure Up 1 and Measure Up 2. ¹ In Measure Up 1, 0.7 percent of patients receiving either upadacitinib 15 mg or 30 mg reported serious infections, and none were observed in patients receiving placebo. ¹ In Measure Up 2, serious infections were reported in 0.4 percent of patients receiving upadacitinib 15 mg and 0.7 percent of patients receiving either upadacitinib 30 mg or placebo. ¹ No deaths, major adverse cardiac events (MACE) or venous thromboembolic events (VTE) were reported in any of the upadacitinib treatment groups in both studies. ¹

Results from these studies are being submitted to journals for publication.

About Atopic Dermatitis

Atopic dermatitis is a chronic, relapsing inflammatory condition characterized by a cycle of intense itching and scratching leading to cracked, scaly, oozing skin. ^6,7 It affects up to an estimated 10 percent of adults and 25 percent of adolescents. ^7,8 Between 20 and 46 percent of adults with atopic dermatitis have moderate to severe disease. ⁹ The range of symptoms pose significant physical, psychological and economic burden on individuals impacted by the disease. ^7,10 Despite advancements in care, patients continue to struggle with the signs and symptoms of the disease. ¹¹

About the Measure Up 1 and Measure Up 2 Studies   ¹

Measure Up 1 and Measure Up 2 are replicate Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled studies designed to evaluate the safety and efficacy of upadacitinib monotherapy 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 upadacitinib 15 mg, upadacitinib 30 mg or placebo, followed by either upadacitinib 15 mg or upadacitinib 30 mg at week 16.

The co-primary endpoints were the percentage of patients achieving EASI 75 and a vIGA-AD score of 0/1 after 16 weeks of treatment. Secondary endpoints included improvement in Worst Pruritus NRS≥4 at week 4 and week 16, EASI 90 at week 16 and DLQI 0/1 at week 16. The trials are 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 in patients who have completed the placebo-controlled period. More information on these trials can be found at www.clinicaltrials.gov (NCT03569293 and NCT03607422).

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. ^1,12-19 It was engineered to have greater inhibitory potency for JAK1 versus JAK2, JAK3 and TYK2. ² 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, giant cell arteritis and Takayasu arteritis are ongoing. ^1,13-19 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) ²⁰

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.

Use in combination with other potent immunosuppressants is not recommended.

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/oesophageal candidiasis, and cryptococcosis have been reported with upadacitinib. Prior to initiating upadacitinib, consider the risks and benefits of treatment in patients with chronic or recurrent infection or with a history of a serious or opportunistic infection, in patients who have been exposed to TB or have resided or travelled in areas of endemic TB or endemic mycoses, and in patients with underlying conditions that may predispose them to infection. Upadacitinib therapy should be interrupted if a patient develops a serious or opportunistic infection. As there is a higher incidence of infections in patients ≥75 years of age, caution should be used when treating this population.

Patients should be screened for TB before starting upadacitinib therapy. Anti-TB therapy should be considered prior to initiation of upadacitinib in patients with previously untreated latent TB or in patients with risk factors for TB infection.

Viral reactivation, including cases of herpes zoster, were reported in clinical studies. Consider interruption of therapy if a patient develops herpes zoster until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed before starting and during therapy with upadacitinib.

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.

The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Immunomodulatory medicinal products may increase the risk of malignancies, including lymphoma. The clinical data are currently limited and long-term studies are ongoing. Malignancies, including non-melanoma 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. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Absolute neutrophil count 3 , absolute lymphocyte count 3 , or haemoglobin levels 1% of patients in clinical trials. Treatment should not be initiated, or should be temporarily interrupted, in patients with these haematological abnormalities observed during routine patient management.

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

Upadacitinib treatment was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.

Treatment with upadacitinib was associated with an increased incidence of liver enzyme elevation compared to placebo. If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, upadacitinib therapy should be interrupted until this diagnosis is excluded.

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. Risk factors that should be considered in determining the patient's risk for DVT/PE include older age, obesity, a medical history of DVT/PE, patients undergoing major surgery, and prolonged immobilisation. If clinical features of DVT/PE occur, upadacitinib treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.

The most commonly reported adverse drug reactions are upper respiratory tract infections (13.5%), nausea (3.5%), increased blood creatine phosphokinase (2.5%), and cough (2.2%). The most common serious adverse reactions were serious infections.

Please see the full SmPC for complete prescribing information at www.EMA.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete information.

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 , 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 .

* Emma Guttman-Yassky , M.D., Ph.D., is a researcher/consultant for AbbVie.

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