AbbVie Presents Data Showing RINVOQ(TM) (upadacitinib) Meets Primary and Key Secondary Endpoints in Phase 3 Head-to-Head Study Versus ORENCIA (abatacept) in Rheumatoid Arthritis Patients

NORTH CHICAGO, Ill., June 6, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced new Phase 3 data from the SELECT-CHOICE clinical trial, showing that RINVOQ™ (upadacitinib, 15 mg, once daily) met the primary endpoint of non-inferiority versus ORENCIA^® (abatacept) on change from baseline in Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) at week 12.¹ In addition, RINVOQ met the key secondary endpoints of superiority versus ORENCIA on change from baseline in DAS28-CRP at week 12 and proportion of patients achieving clinical remission at week 12 as measured by DAS28-CRP<2.6.¹ The study evaluated RINVOQ in adult patients with moderate to severe active rheumatoid arthritis and prior inadequate response or intolerance to biologic disease-modifying anti-rheumatic drugs (DMARDs). Full results were presented today at the 2020 Annual European E-Congress of Rheumatology (EULAR).

SELECT-CHOICE is the sixth and final Phase 3 study from the robust SELECT rheumatoid arthritis clinical trial program.^1,2 RINVOQ, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is approved 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 DMARDs.²

"Despite tremendous progress in the treatment of rheumatoid arthritis, about 70 percent of patients are still not achieving clinical remission with established therapies," said Michael Severino, M.D., vice chairman and president, AbbVie. "We are pleased with the results as they add to our growing body of evidence that RINVOQ may offer more adult patients with rheumatoid arthritis a better chance at achieving clinical remission, including those who have already failed a prior biologic."

"These data show that upadacitinib was superior to abatacept with regard to the proportion of patients achieving remission," said Professor Andrea Rubbert-Roth, M.D., deputy director, Division of Rheumatology, Cantonal Hospital St. Gallen, Switzerland. "SELECT-CHOICE represents the first head-to-head study in rheumatoid arthritis patients who have failed biologic DMARDs and compares upadacitinib to a different biologic DMARD. Studies like this are important for daily decision-making in practice."

In this study, RINVOQ met both the primary (non-inferiority) and secondary (superiority) endpoints, with a change from baseline in DAS28-CRP at week 12 of -2.52 compared to -2.00 in patients treated with ORENCIA.¹ In addition, 30 percent of patients receiving RINVOQ achieved clinical remission at week 12 (DAS28-CRP<2.6) compared to 13 percent of patients receiving ORENCIA (p<0.001).¹

ACR20/50/70 responses were also higher in the RINVOQ group compared to the ORENCIA group (76/46/22 percent versus 66/34/14 percent, respectively, nominal p<0.05) at week 12.¹ Improvements in disease activity and remission rates were maintained through 24 weeks.¹

The safety profile of RINVOQ (15 mg) was consistent with that observed in previously reported studies in rheumatoid arthritis, with no new safety risks detected.¹ Through week 24, serious adverse events occurred in 3.3 percent of patients in the RINVOQ group, compared to 1.6 percent of patients in the ORENCIA group.¹ There were three cases of serious infection reported in the RINVOQ group and one in the ORENCIA group.¹ There were also 23 cases of hepatic disorder (primarily liver enzyme elevations) in the RINVOQ group compared to five cases of hepatic disorder in the ORENCIA group.¹ All hepatic disorder events were non-serious.³ Most of the events were transient ALT/AST elevations and considered mild to moderate in severity.³ None led to study drug interruption.³ Four cases of herpes zoster were reported in the RINVOQ group and four cases in the ORENCIA group.¹ Across both groups, there were no malignancies reported.¹ One major adverse cardiovascular event (MACE) and two adjudicated cases of venous thromboembolic events (VTE) were reported in the RINVOQ group, and both patients had at least one risk factor for VTE.¹ There were no MACE and VTE reported in the ORENCIA group.¹ There were two deaths in the RINVOQ group, one of which was non-treatment emergent, as well as one non-treatment emergent death in the ORENCIA group.¹

About SELECT-CHOICE¹

SELECT-CHOICE is a Phase 3, multicenter, randomized, double-blind, active-controlled study designed to evaluate the safety and efficacy of RINVOQ in combination with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) compared to ORENCIA (abatacept) in combination with csDMARDs in adult patients with moderate to severe active rheumatoid arthritis who have an inadequate response to or intolerance to biologic DMARDs. Patients were randomized to once daily RINVOQ (15 mg) or intravenous ORENCIA (at day 1, weeks 2, 4, 8, 12, 16 and 20 [<60 kg: 500 mg; 60-100 kg: 750 mg; >100 kg: 1,000 mg]), with all patients continuing background stable csDMARDs.

The primary endpoint was change from baseline in DAS28-CRP at week 12 showing non-inferiority in patients receiving RINVOQ (15 mg) compared to those receiving ORENCIA. Ranked secondary endpoints included superiority to ORENCIA in terms of change from baseline in DAS28-CRP at week 12 and proportion of patients achieving clinical remission, as defined by DAS28-CRP<2.6 at week 12. More information on this trial can be found at www.clinicaltrials.gov (NCT03086343).

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.^{1, 2, 4-12} 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, 4-12} 

Important EU Safety Information about RINVOQ™ (upadacitinib)²

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 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. Efficacy and Safety of Upadacitinib Versus Abatacept in Patients With Active Rheumatoid Arthritis and Prior Inadequate Response or Intolerance to Biologic Disease-modifying Anti-rheumatic Drugs (SELECT-CHOICE): A Double-Blind, Randomized Controlled Phase 3 Trial. 2020 EULAR E-Congress; SAT0151.
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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 May 18, 2020.
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