AbbVie Submits Regulatory Applications to FDA and EMA for RINVOQ™ (upadacitinib) for the Treatment of Adults with Active Psoriatic Arthritis

NORTH CHICAGO, Ill., June 1, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced that it has submitted applications for a new indication to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for RINVOQ™ (upadacitinib; 15 mg, once daily), a selective and reversible JAK inhibitor, for the treatment of adult patients with active psoriatic arthritis.

"Psoriatic arthritis is a complex heterogeneous disease with manifestations across multiple domains, including joints and skin, causing daily pain, fatigue and stiffness," said Michael Severino, M.D., vice chairman and president, AbbVie. "We look forward to working with regulatory authorities and hope to bring RINVOQ to people living with this debilitating disease as quickly as possible."

The applications are supported by data from two Phase 3 studies across a broad range of more than 2,000 patients with active psoriatic arthritis.^1,2 In both studies, RINVOQ met the primary endpoint of ACR20 response at week 12 versus placebo.^1,2 RINVOQ 15 mg also achieved non-inferiority versus adalimumab in terms of ACR20 response at week 12.¹ Patients receiving RINVOQ also experienced greater improvements in physical function (HAQ-DI) and skin symptoms (PASI 75), and a greater proportion achieved minimal disease activity.*^,1,2 Overall, the safety profile of RINVOQ in psoriatic arthritis was consistent with previously reported results across the Phase 3 rheumatoid arthritis clinical trial program, with no new significant safety risks detected.^1-3

*Physical function was measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). Skin symptoms were measured by a 75 percent improvement in the Psoriasis Area Severity Index (PASI 75). Minimal disease activity is defined as the fulfillment of five of seven outcome measures: Tender joint count ≤1; swollen joint count ≤1; PASI ≤1 or body surface area-psoriasis ≤3 percent; Patient's Assessment of Pain Numerical Rating Scale (NRS) ≤1.5; Patient Global Assessment-Disease Activity NRS ≤2.0; HAQ-DI score ≤0.5; and Leeds Enthesitis Index ≤1.

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.^1,2,4-10 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 psoriatic arthritis, rheumatoid arthritis, axial spondyloarthritis, Crohn's disease, atopic dermatitis, ulcerative colitis and giant cell arteritis are ongoing.^1,2,4-10 Use of RINVOQ in psoriatic arthritis is not approved and its safety and efficacy have not been established by regulatory authorities.

Important Safety Information about RINVOQ (upadacitinib)¹¹

RINVOQ U.S. Use and Important Safety Information
RINVOQ is a prescription medicine used to treat adults with moderate to severe rheumatoid arthritis in whom methotrexate did not work well or could not be tolerated. It is not known if RINVOQ is safe and effective in children under 18 years of age.

What is the most important information I should know about RINVOQ?
RINVOQ is a medicine that can lower the ability of your immune system to fight infections. You should not start taking RINVOQ if you have any kind of infection unless your healthcare provider (HCP) tells you it is okay.

• Serious infections have happened in some people taking RINVOQ, including tuberculosis (TB) and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Your HCP should test you for TB before starting RINVOQ and check you closely for signs and symptoms of TB during treatment with RINVOQ. You may be at higher risk of developing shingles (herpes zoster).
• Lymphoma and other cancers, including skin cancers, can happen in people taking RINVOQ.
• Blood clots in the veins of the legs or lungs and arteries are possible in some people taking RINVOQ. This may be life-threatening and cause death.
• Tears in the stomach or intestines and changes in certain laboratory tests can happen. Your HCP should do blood tests before you start taking RINVOQ and while you take it. Your HCP may stop your RINVOQ treatment for a period of time if needed because of changes in these blood test results.

What should I tell my HCP BEFORE starting RINVOQ?
Tell your HCP if you:

• Are being treated for an infection, have an infection that won't go away or keeps coming back, or have symptoms of an infection such as:
• Fever, sweating, or chills
• Shortness of breath
• Warm, red, or painful skin or sores on your body
• Muscle aches
• Feeling tired
• Blood in phlegm
• Diarrhea or stomach pain
• Cough
• Weight loss
• Burning when urinating or urinating more often than normal
• Have TB or have been in close contact with someone with TB.
• Have had any type of cancer, hepatitis B or C, shingles (herpes zoster), or blood clots in the veins of your legs or lungs, diverticulitis (inflammation in parts of the large intestine), or ulcers in your stomach or intestines.
• Have other medical conditions including liver problems, low blood cell counts, diabetes, chronic lung disease, HIV, or a weak immune system.
• Live, have lived, or have traveled to parts of the country that increase your risk of getting certain kinds of fungal infections, such as the Ohio and Mississippi River valleys and the Southwest. If you are unsure if you've been to these areas, ask your HCP.
• Have recently received or are scheduled to receive a vaccine. People who take RINVOQ should not receive live vaccines.
• Are pregnant or plan to become pregnant. Based on animal studies, RINVOQ may harm your unborn baby. Your HCP will check whether or not you are pregnant before you start RINVOQ. You should use effective birth control (contraception) to avoid becoming pregnant while taking RINVOQ and for at least 4 weeks after your last dose.
• Are breastfeeding or plan to breastfeed. RINVOQ may pass into your breast milk. You should not breastfeed while taking RINVOQ and for at least 6 days after your last dose.

Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RINVOQ and other medicines may affect each other, causing side effects.

Especially tell your HCP if you take:

• Medicines for fungal or bacterial infections
• Rifampicin or phenytoin
• Medicines that affect your immune system

Ask your HCP or pharmacist if you are not sure if you are taking any of these medicines.

What should I tell my HCP AFTER starting RINVOQ?
Tell your HCP right away if you:

• Have any symptoms of an infection. RINVOQ can make you more likely to get infections or make any infections you have worse.
• Have any signs or symptoms of blood clots during treatment with RINVOQ, including:
• Swelling
• Sudden unexplained chest pain
• Pain or tenderness in the leg
• Shortness of breath
• Have a fever or stomach-area pain that does not go away, and a change in your bowel habits.

What are the common side effects of RINVOQ?
These include: upper respiratory tract infections (common cold, sinus infections), nausea, cough, and fever. These are not all the possible side effects of RINVOQ.

RINVOQ is taken once a day with or without food. Do not split, break, crush, or chew the tablet. Take RINVOQ exactly as your HCP tells you to use it.

This is the most important information to know about RINVOQ. For more information, talk to your HCP. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

If you are having difficulty paying for your medicine, AbbVie may be able to help. Visit AbbVie.com/myAbbVieAssist to learn more.

Please click here for the Full Prescribing Information and Medication Guide.

Important EU Safety Information about RINVOQ (upadacitinib)¹²

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, the possibility that the proposed acquisition of Allergan will not be pursued, failure to obtain necessary regulatory approvals or required financing or to satisfy any of the other conditions to the proposed acquisition, failure to realize the expected benefits of the proposed acquisition, failure to promptly and effectively integrate Allergan's businesses, significant transaction costs and/or unknown or inestimable liabilities, potential litigation associated with the proposed acquisition, challenges to intellectual property, competition from other products, 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 (SEC). 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. McInnes I, et al. Efficacy and Safety of Upadacitinib Versus Placebo and Adalimumab in Patients With Active Psoriatic Arthritis and Inadequate Response to Non-Biologic Disease-Modifying Anti-Rheumatic Drugs (SELECT-PsA-1): a Double-Blind, Randomized Controlled Phase 3 Trial. 2020 EULAR E-Congress; LB0001.
2. Genovese MC, et al. Efficacy and Safety of Upadacitinib in Patients With Active Psoriatic Arthritis and Inadequate Response to Biologic Disease-Modifying Anti-Rheumatic Drugs (SELECT-PsA-2): a Double-Blind, Randomized Controlled Phase 3 Trial. 2020 EULAR E-Congress; OP0223.
3. Cohen S., et al. Safety profile of upadacitinib in Rheumatoid Arthritis: Integrated analysis from the SELECT Phase 3 Clinical Program. EULAR 2019; THU0167.
4. Pipeline – Our Science | AbbVie. AbbVie. 2019. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on May 8, 2020.
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6. 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 8, 2020.
7. 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 8, 2020.
8. 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 8, 2020.
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 8, 2020.
10. 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 8, 2020.
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12. 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.

SOURCE AbbVie

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