New Long-term Data from RINVOQ™ (upadacitinib, 15 mg) Phase 3 Studies in Rheumatoid Arthritis Presented at 2020 Annual European E-Congress of Rheumatology (EULAR)

NORTH CHICAGO, Ill., June 4, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced new long-term results showing that once daily upadacitinib continued to improve signs and symptoms in patients with rheumatoid arthritis at 72 and 84 weeks in the SELECT-COMPARE (upadacitinib, 15 mg in combination with methotrexate [MTX]) and SELECT-MONOTHERAPY (upadacitinib, 15 mg and 30 mg) Phase 3 clinical trials, respectively.^1,2 The safety profile of upadacitinib (15 mg and 30 mg) monotherapy or upadacitinib (15 mg) in combination with MTX was consistent with that observed in the previously reported integrated Phase 3 safety analysis in rheumatoid arthritis, with no new safety risks detected.^1-5

Additionally, approximate two-year data (96 weeks) from the SELECT-EARLY (upadacitinib, 15 mg and 30 mg) and SELECT-COMPARE clinical trials showed that upadacitinib was effective in inhibiting structural joint damage as monotherapy or in combination with MTX.³ Full results were presented today at the 2020 Annual European E-Congress of Rheumatology (EULAR).

RINVOQ™, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is approved as an oral, once daily, 15 mg therapy for adults with moderate to severe active rheumatoid arthritis.^1-5

"These new long-term data showcase the potential of RINVOQ to provide relief from the signs and symptoms of rheumatoid arthritis, both as a monotherapy and in combination with methotrexate," said Isidro Villanueva, vice president, medical affairs immunology, AbbVie. "We are excited to share these results with the rheumatology community reinforcing RINVOQ as an important treatment option that may help more patients living with rheumatoid arthritis reach their goals in disease management."

SELECT-COMPARE Results at 72 Weeks
Results of this Long-Term Extension (LTE) of the SELECT-COMPARE study show that RINVOQ plus MTX maintained higher levels of clinical response, including remission compared to adalimumab plus MTX, through week 72.¹

The safety profile of RINVOQ (15 mg) in combination with MTX was generally consistent with that observed in the previously reported integrated Phase 3 safety analysis in rheumatoid arthritis, with no new safety risks detected.^1,4 Through the data cut-off, serious adverse events (SAEs) occurred at 12.7 events/100PY (per 100 patient years) on RINVOQ (15 mg) in combination with MTX, compared to 15.9 events/100PY on adalimumab in combination with MTX.¹ The rate of serious infections was 3.7 events/100PY on RINVOQ (15 mg) plus MTX and 4.3 events/100PY on adalimumab plus MTX.¹ There were eight deaths on RINVOQ (0.6/100PY) and six deaths on adalimumab (1.2/100PY), including non-treatment emergent deaths.¹ There were eight major adverse cardiac events (MACE) through the study duration, including five on RINVOQ (0.4/100PY) and three on adalimumab (0.6/100PY).¹ There were four patients with venous thromboembolic events (VTE) reported on RINVOQ (0.3/100PY) and five reported on adalimumab (1.0/100 PY).¹

SELECT-MONOTHERAPY Results at 84 Weeks
In this LTE of the SELECT-MONOTHERAPY study, patients who received continued MTX in the first phase of the study were switched to receive blinded upadacitinib (15 mg or 30 mg) at week 14 based on pre-specified assignment at baseline.² Results of this LTE show that upadacitinib monotherapy resulted in continued improvements in rheumatoid arthritis signs and symptoms through 84 weeks.²

The safety profile of upadacitinib (15 mg and 30 mg) monotherapy at week 84 was generally consistent with that observed in the previously reported integrated Phase 3 safety analysis in rheumatoid arthritis, with no new safety risks detected.^2,4 Through week 84, SAEs occurred at 18.5 events/100PY (per 100 patient years) on upadacitinib 15 mg and 16.9 events/100PY on upadacitinib 30 mg.² The most common SAE was pneumonia.² Events of herpes zoster, hepatic disorder and creatine phosphokinase elevations were higher among patients receiving upadacitinib 30 mg, while rates of serious infection and malignancy were comparable between upadacitinib 30 mg and 15 mg.² Seven patients experienced MACE (15 mg, 0.5/100 PY; 30 mg, 1.2/100 PY) and there were five VTE (15 mg, 0.9/100 PY; 30 mg, 0.2/100 PY).² All MACE and VTE occurred in patients with underlying risk factors.² There were three deaths each (0.7/100PY) on upadacitinib 15 mg and 30 mg, including non-treatment emergent deaths.²

Radiographic Inhibition at Approximately Two Years: SELECT-EARLY and SELECT-COMPARE
Both SELECT-EARLY and SELECT-COMPARE enrolled rheumatoid arthritis patients at high risk for progressive structural damage with baseline erosive joint damage and/or seropositivity.³ RINVOQ inhibited structural joint damage in MTX-naïve patients receiving RINVOQ monotherapy and in patients with an inadequate response to MTX in combination with MTX.³

About RINVOQ™ (upadacitinib, 15 mg)

Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.^5-14 In August 2019, RINVOQ received U.S. FDA 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 was approved 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 rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, atopic dermatitis, ulcerative colitis and giant cell arteritis are ongoing.^1-3,7-14

About SELECT-COMPARE¹

SELECT-COMPARE is a Phase 3, multicenter, randomized, double-blind study designed to evaluate the safety and efficacy of RINVOQ compared to placebo and adalimumab in adult patients with moderate to severe active rheumatoid arthritis who had an inadequate response to methotrexate and continued a stable background of MTX. Patients received background MTX and were randomized 2:2:1 to receive RINVOQ (15 mg, once daily), placebo or adalimumab (given as a subcutaneous injection of 40 mg every other week).

The primary endpoints of the first phase included the percentage of subjects achieving ACR20 and clinical remission (based on DAS28-CRP) after 12 weeks of treatment compared to placebo. Ranked secondary endpoints included change in the mTSS compared to placebo and a comparison versus adalimumab in percentage of subjects achieving ACR50, low disease activity, changes in pain as measured by the Patient's Assessment of Pain (based on VAS) and changes in physical function, as measured by the Health Assessment Questionnaire-Disability-Index (HAQ-DI). The trial is ongoing and included a 48-week randomized, double-blind treatment period followed by a long-term extension study of up to five years.

More information on this trial can be found at www.clinicaltrials.gov (NCT02629159).

About SELECT-MONOTHERAPY²

SELECT-MONOTHERAPY is a Phase 3, multicenter, randomized, double-blind, parallel-group study designed to evaluate the safety and efficacy of upadacitinib monotherapy in adult patients with moderate to severe active rheumatoid arthritis and an inadequate response to a stable dose of methotrexate. Patients were randomized to switch from MTX to upadacitinib monotherapy (15 mg or 30 mg, once daily) or continue on their prior stable dose of MTX in a blinded manner.

The primary endpoints of the first phase included the percentage of patients achieving an ACR20 response and low disease activity after 14 weeks of treatment. Secondary endpoints included proportion of patients achieving ACR50, ACR70 and clinical remission at week 14, HAQ-DI, duration of morning stiffness and health-related quality of life (QoL) by SF-36. The trial is ongoing, and the second phase is a blinded long-term extension period to evaluate the long-term safety, tolerability and efficacy of the two once daily doses of upadacitinib (15 mg and 30 mg) monotherapy in patients who have completed the first phase.

More information on this trial can be found at www.clinicaltrials.gov (NCT02706951).

About SELECT-EARLY³

SELECT-EARLY is a Phase 3, multicenter, randomized, double-blind, parallel-group, active comparator controlled study designed to evaluate the safety and efficacy of upadacitinib monotherapy compared to MTX monotherapy in adult patients with moderate to severe active rheumatoid arthritis who are MTX-naïve. In the first phase of the study, patients were randomized 1:1:1 to receive upadacitinib (15 mg or 30 mg, once daily) or MTX. It includes a Japan sub-study in which subjects were randomized 2:1:1:1 to receive upadacitinib (7.5 mg, 15 mg or 30 mg, once daily) or MTX.

The primary endpoints included the percentage of subjects achieving ACR50 response and clinical remission (based on DAS28-CRP) compared to MTX after 12 weeks and 24 weeks of treatment, respectively. Ranked secondary endpoints included the percentage of patients achieving ACR20 response, ACR70 response and low disease activity, as well as changes in the mTSS and HAQ-DI. The trial is ongoing and includes a 48-week randomized, double-blind treatment period followed by a long-term extension period for up to an additional four years.

More information on this trial can be found at www.clinicaltrials.gov (NCT02706873).

Important EU Safety Information about RINVOQ™ (upadacitinib)⁵

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 <1000 cells/mm³, absolute lymphocyte count <500 cells/mm³, or haemoglobin levels <8 g/dL were reported in <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.

About HUMIRA^® in the European Union¹⁵

HUMIRA, in combination with methotrexate, is indicated for the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying anti-rheumatic drugs, including methotrexate, has been inadequate.

Important EU Safety Information about HUMIRA^® (adalimumab)¹⁵

HUMIRA is contraindicated in patients with active tuberculosis or other severe infections such as sepsis, and opportunistic infections and in patients with moderate to severe heart failure (NYHA class III/IV). It is also contraindicated in patients hypersensitive to the active substance or to any of the excipients; serious allergic reactions including anaphylaxis have been reported. The use of HUMIRA increases the risk of developing serious infections, including hepatitis B reactivation, which may, in rare cases, be life-threatening. Rare cases of lymphoma and leukemia have been reported in patients treated with HUMIRA. On rare occasions, a severe type of cancer called hepatosplenic T-cell lymphoma has been observed and often results in death. A risk for the development of malignancies in patients treated with TNF-antagonists cannot be excluded. Rare cases of pancytopenia, aplastic anaemia, demyelinating disease, lupus, lupus-related conditions and Stevens-Johnson syndrome have been reported in patients treated with HUMIRA. The most frequently reported adverse events across all indications included respiratory infections, injection site reactions, headache and musculoskeletal pain.

About AbbVie in Rheumatology

For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Our longstanding commitment to discovering and delivering transformative therapies is underscored by our pursuit of cutting-edge science that improves our understanding of promising new pathways and targets in order to help more people living with rheumatic diseases reach their treatment goals. For more information on AbbVie in rheumatology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/rheumatology.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, 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 2019 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. Fleischmann R, et al. Long-Term Safety and Effectiveness of Upadacitinib or Adalimumab in Patients with Rheumatoid Arthritis: Results at 72 weeks from the SELECT-COMPARE Study. 2020 EULAR E-Congress; THU0201.
2. Smolen J, et al. Upadacitinib as Monotherapy in Patients with Rheumatoid Arthritis and Prior Inadequate Response to Methotrexate: Results at 84 Weeks From the SELECT-MONOTHERAPY Study. 2020 EULAR E-Congress; THU0213.
3. Peterfy CG, et al. Radiographic Outcomes in Patients with Rheumatoid Arthritis Receiving Upadacitinib as Monotherapy or in Combination with Methotrexate: Results at 2 years from the SELECT-COMPARE and SELECT-EARLY Studies. 2020 EULAR E-Congress; THU0211.
4. Cohen S, et al. Safety Profile of Upadacitinib Up to 3 Years of Exposure in Patients With Rheumatoid Arthritis. 2020 EULAR E-Congress; THU0197.
5. RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; March 2020. Available at: https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
6. Pipeline – Our Science | AbbVie. AbbVie. 2020. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on May 18, 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 May 18, 2020.
8. 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 May 18, 2020.
9. Evaluation of Upadacitinib in Adolescent and Adult Patients With Moderate to Severe Atopic Dermatitis (Eczema)- Measure Up 1. ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03569293. Accessed on May 18, 2020.
10. 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 May 18, 2020.
11. 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 May 18, 2020.
12. 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 May 18, 2020.
13. A Study Comparing Upadacitinib (ABT-494) to Placebo in Participants With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Biologic Disease Modifying Anti-Rheumatic Drug (SELECT - PsA 2). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03104374. Accessed on May 18, 2020.
14. A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed on May 18, 2020.
15. HUMIRA [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co KG. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000481/WC500050870.pdf. Accessed May 18, 2020.

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