AbbVie Receives European Commission Approval of RINVOQtm (upadacitinib) for the Treatment of Adults with Moderate to Severe Active Rheumatoid Arthritis

NORTH CHICAGO, Ill., Dec. 18, 2019 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced that the European Commission (EC) has approved RINVOQtm (upadacitinib) 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 (DMARDs).⁶ RINVOQ is a once-daily selective and reversible JAK inhibitor and may be used as monotherapy or in combination with methotrexate (MTX).

"We are proud to offer this once-daily tablet as a new treatment option for patients with moderate to severe active rheumatoid arthritis," said Michael Severino, M.D., vice chairman and president, AbbVie. "As a company that has been dedicated to discovering and delivering transformative therapies for people living with rheumatic diseases for nearly two decades, RINVOQ expands our portfolio of treatment options for people living with this disease in Europe."

The EC approval of RINVOQ was supported by data from the global Phase 3 SELECT rheumatoid arthritis program, which evaluated nearly 4,400 patients with moderate to severe active rheumatoid arthritis in five pivotal studies: SELECT-NEXT, SELECT-BEYOND, SELECT-MONOTHERAPY, SELECT-COMPARE and SELECT-EARLY.^1-5 The studies include assessments of efficacy, safety and tolerability across a variety of patients, including those who failed or were intolerant to biologic DMARDs and who were naïve or inadequate responders (IR) to MTX.^1-5

"Nearly 3 million people in Europe are living with rheumatoid arthritis, the majority of whom don't reach remission and may be suffering from pain, fatigue, morning joint stiffness and flares," said Professor Ronald van Vollenhoven, M.D., Ph.D., Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands. "As seen in this large Phase 3 clinical trial program in rheumatoid arthritis, upadacitinib has the potential to significantly improve signs and symptoms of the disease and help more patients achieve remission or low disease activity."

Highlights From the Phase 3 SELECT Rheumatoid Arthritis Program

Across the SELECT Phase 3 studies, RINVOQ met all primary and ranked secondary endpoints.^1-6 Overall, both low disease activity (assessed by DAS28-CRP?3.2) and clinical remission rates (assessed by DAS28-CRP<2.6) were consistent across patient populations, with or without MTX.^1-6

Highlights included:

• In SELECT-COMPARE, RINVOQ plus MTX demonstrated significantly higher remission rates (as observed by DAS28-CRP<2.6) versus placebo plus MTX (29 percent vs 6 percent at week 12; multiplicity-controlled p?0.001) and vs HUMIRA^® (adalimumab) plus MTX (29 percent vs 18 percent at week 12; nominal p?0.001) in MTX-IR patients.⁴
• More patients treated with RINVOQ alone achieved remission (as observed by DAS28-CRP<2.6) than those treated with MTX in MTX-IR patients in SELECT-MONOTHERAPY (28 percent vs 8 percent at week 14; multiplicity-controlled p?0.0001) and in MTX-naïve patients in SELECT-EARLY (48 percent vs 18 percent at week 24; multiplicity-controlled p<0.001).^3,5
• RINVOQ also demonstrated significantly greater inhibition of structural joint damage progression, as measured by modified total Sharp score change from baseline, as monotherapy compared to MTX (0.1 vs 0.7 at week 24; multiplicity-controlled p<0.01) in MTX-naïve patients and in combination with MTX compared to placebo plus MTX (0.2 vs 0.9 at week 26; multiplicity-controlled p?0.001) in MTX-IR patients.^4,5
• The most commonly reported adverse drug reactions were upper respiratory tract infections (13.5 percent), nausea (3.5 percent), blood creatine phosphokinase increased (2.5 percent) and cough (2.2 percent).⁶ The most common serious adverse reactions were serious infections.^1-6

More information on these trials can be found at www.clinicaltrials.gov (NCT02706847, NCT03086343, NCT02629159, NCT02706873, NCT02706951).

Earlier this year, RINVOQ received approval from the U.S. Food and Drug Administration (FDA) for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to MTX.⁹

About RINVOQ (upadacitinib) in the European Union⁶

RINVOQ (upadacitinib) 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.

Important EU Safety Information⁶

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 Union¹⁰

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 Information¹⁰

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 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.

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

AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. 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, 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 2018 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. Burmester GR, 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 13.
2. Genovese MC, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet. 2018 Jun 23;391(10139):2513-2524. doi: 10.1016/S0140-6736(18)31116-4. Epub 2018 Jun 13.
3. Smolen JS, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet. 2019. May 23. doi: 10.1016/S0140-6736(19)30419-2. Epub 2019 May 23.
4. Fleischmann R, et al. Upadacitinib versus placebo or adalimumab in rheumatoid arthritis and an inadequate response to methotrexate: Results of a Phase 3, Double-Blind, Randomized Controlled Trial. Arthritis and Rheumatology. 2019. Jul 9. doi: 10.1002/art.41032.
5. van Vollenhoven R, et al. A Phase 3, Randomized, Controlled Trial Comparing Upadacitinib Monotherapy to MTX Monotherapy in MTX-Naïve Patients with Active Rheumatoid Arthritis. 2018 ACR/ARHP Annual Meeting; 891.
6. RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co KG. Available at: www.ema.europa.eu
7. Bevan S, et al. Fit For Work? Musculoskeletal Disorders in the European Workforce. 2009. The Work Foundation.
8. Ajeganova S. and Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv Musculoskelet Dis. 2017 Oct;9(10):249-262. doi: 10.1177/1759720X17720366.
9. RINVOQtm (upadacitinib) [Package Insert]. North Chicago, Ill.: AbbVie Inc.
10. 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 November 12, 2019.

SOURCE AbbVie