ABBVie (NYSE: ABBV) today announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the approval of RINVOQ ® (upadacitinib), an oral, selective and reversible JAK inhibitor, for the expanded use in adults (15 mg or 30 mg, once daily) and adolescents 12 years and older (15 mg, once daily) with moderate to severe atopic dermatitis who are candidates for systemic therapy. RINVOQ is being studied in several immune-mediated inflammatory diseases. 4-10
The CHMP positive opinion was supported by data from the global Phase 3 program evaluating more than 2,500 patients with moderate to severe atopic dermatitis across three global pivotal studies: Measure Up 1, Measure Up 2 and AD Up. 1,2 Across the three studies, both doses of RINVOQ met all primary and secondary endpoints, demonstrating rapid and significant improvement in skin clearance and reduction in itch compared to placebo at week 16 and other time points (p 1,2 The most commonly reported adverse events in patients treated with RINVOQ were acne, nasopharyngitis and upper respiratory tract infections. 1,2
"This milestone is an important step forward in our journey to improve care for people living with atopic dermatitis," said Michael Severino , M.D., vice chairman and president, AbbVie. "Despite available treatments, many people with moderate to severe forms of this disease continue to experience a relentless and burdensome cycle of skin and itch symptoms. We are encouraged that the CHMP has recognized RINVOQ's potential as an additional treatment option for these patients."
The CHMP positive opinion is a scientific recommendation for marketing authorization to the European Commission, which authorizes marketing approval in the European Union. The Marketing Authorization will be valid in all member states of the European Union, as well as Iceland , Liechtenstein , Norway and Northern Ireland . If approved, this will be the fourth indication for RINVOQ, and RINVOQ will be the first JAK inhibitor in the European Union to treat moderate to severe atopic dermatitis in both adults and adolescents 12 years and older. 3
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. 11,12 It affects up to an estimated 10 percent of adults and 25 percent of children. 12,13 Between 20 and 46 percent of adults with atopic dermatitis have moderate to severe disease. 14 The range of symptoms poses significant physical, psychological and economic burden on individuals impacted by the disease. 12,15
About the RINVOQ Atopic Dermatitis Global Phase 3 Study Program
The global Phase 3 program evaluated more than 2,500 patients worldwide across three global pivotal studies: Measure Up 1, Measure Up 2 and AD Up. 1,2 The studies evaluated the efficacy and safety of RINVOQ (15 mg and 30 mg, once daily), with and without topical corticosteroids (TCS), in adults and adolescents with moderate to severe atopic dermatitis who were candidates for systemic therapy. 1,2 The co-primary endpoints across all three studies were at least a 75 percent improvement in Eczema Area and Severity Index (EASI 75) and a validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) score 0/1 at week 16. 1,2 Secondary endpoints included reduction of itch defined as ≥4 point improvement in Worst Pruritus Numerical Rating Scale (NRS) from baseline at week 16 and other timepoints, as well as EASI 90 and EASI 100 at week 16. 1,2 More information on this program can be found at www.clinicaltrials.gov (NCT03569293, NCT03607422, NCT03568318).
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. 1-10 In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2. 3 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. RINVOQ is 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 (DMARDs); for the treatment of active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs; and for the treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy. The approved dose for RINVOQ in these indications is 15 mg. Phase 3 trials of RINVOQ in axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing. 4-10 Use of RINVOQ in atopic dermatitis is not approved and its safety and efficacy are under evaluation by regulatory authorities.
Important EU Safety Information about RINVOQ ® (upadacitinib) 3
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 ≥65 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. The risk of herpes zoster appears to be higher in Japanese patients treated with upadacitinib. 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 were upper respiratory tract infections, bronchitis, nausea, blood creatine phosphokinase (CPK) increased and cough. The most common serious adverse reactions were serious infections.
Overall, the safety profile observed in patients with active psoriatic arthritis treated with upadacitinib 15 mg was consistent with rheumatoid arthritis. A higher incidence of acne and bronchitis was observed in patients treated with upadacitinib compared to placebo. A higher rate of serious infections and hepatic transaminase elevations was observed in patients treated with upadacitinib in combination with MTX compared to monotherapy.
Please see the full SmPC for complete prescribing information at http://www.EMA.europa.eu .
Globally, prescribing information varies; refer to the individual country product label for complete information.
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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 2020 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.
- Guttman-Yassky E ., et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate, double-blind, randomized controlled phase 3 studies. Lancet. doi:10.1016/s0140-6736(21)00588-2.
- Reich K., et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomized, double-blind, placebo-controlled phase 3 trial. Lancet. doi:10.1016/s0140-6736(21)00589-4.
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; May 2021 . Available at: https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
- Pipeline – Our Science | AbbVie. AbbVie. 2021. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on June 1, 2021.
- A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis (Heads Up). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03738397. Accessed on June 1, 2021.
- A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed on June 1, 2021.
- 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. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on Accessed on June 1, 2021.
- A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Ulcerative Colitis (U-ACCOMPLISH). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03653026. Accessed on June 1, 2021.
- A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed on June 1, 2021.
- A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (TAK) (SELECT-TAK). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04161898 . Accessed on June 1, 2021.
- Nutten S. Atopic Dermatitis: Global Epidemiology and Risk Factors. Ann Nutr Metab 2015;66(suppl 1):8–16. doi: 10.1159/000370220.
- Weidinger, S., et al. Atopic dermatitis. Nat Rev Dis Primers 4, 1(2018). doi: 10.1038/s41572-018-0001-z.
- Eichenfield L.F., et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338-351. doi:10.1016/j.jaad.2013.10.010.
- Shrestha S., et al. Burden of Atopic Dermatitis in the United States : Analysis of Healthcare Claims Data in the Commercial, Medicare, and Medi-Cal Databases. Adv Ther . 2017;34(8):1989–2006.
- EFA. Atopic Eczema: Itching for Life Report. 2018. Available at: https://www.efanet.org/images/2018/EN_-_Itching_for_life_Quality_of_Life_and_costs_for_people_with_severe_atopic_eczema_in_Europe_.pdf . Accessed on June 1, 2021 .