AbbVie Announces European Commission Approval of RINVOQ® (upadacitinib) for the Treatment of Adults with Giant Cell Arteritis

RINVOQ is the first and only oral Janus kinase (JAK) inhibitor approved in the European Union (EU) to treat adult patients with giant cell arteritis (GCA) The approval is supported by data from the pivotal Phase 3 SELECT-GCA trial which demonstrated that RINVOQ achieved the primary endpoint of sustained remission* and key secondary endpoints, including reduction in disease flares, lower cumulative steroid exposure and complete remission †1 This marks the eighth approved indication for RINVOQ in the EU2 , /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the European Commission (EC) granted marketing authorization to RINVOQ® (upadacitinib; 15 mg, once daily) for the treatment of giant cell arteritis (GCA) in adult patients. RINVOQ is the first and only oral JAK inhibitor approved in the EU, as well as Iceland, Liechtenstein and Norway, for the treatment of adult patients with GCA. "GCA is a challenging and often debilitating condition. Patients may endure headaches, jaw pain and muscle aches, with many fearing sudden and permanent vision loss,"3 said Prof. Dr. med. Wolfgang Schmidt, M.D., MACR, Waldfriede Hospital, Department of Rheumatology, Berlin, Germany, and SELECT-GCA trial investigator. "Results from the SELECT-GCA trial show that patients can achieve sustained remission and reduce their cumulative steroid exposure with RINVOQ, addressing important patient goals in the treatment of GCA." GCA is an autoimmune disease that causes inflammation of the temporal and other cranial arteries, the aorta, and other large and medium arteries. GCA generally impacts patients older than 50 years, most commonly between the ages of 70 and 80 years.3 "The EC approval of RINVOQ in GCA provides patients and physicians with a new treatment option and the first oral advanced therapy for adults living with GCA – a particularly vulnerable population due to older age and frequent comorbidities,"3,4 said Roopal Thakkar, M.D., executive vice president, research & development, chief scientific officer, AbbVie. "This exciting milestone demonstrates our commitment to ongoing research and expanding indications in areas of high unmet need to help patients achieve better outcomes, including sustained disease remission." The EC approval is supported by data from the Phase 3 SELECT-GCA trial, which was recently published in the New England Journal of Medicine.1 In this trial, primary and key secondary endpoints were achieved with RINVOQ 15 mg and a 26-week steroid taper regimen compared to placebo in combination with a 52-week steroid taper regimen.1 Primary endpoint results from the Phase 3 SELECT-GCA trial demonstrated: Sustained remission*: 46.4% of patients receiving RINVOQ 15 mg in combination with a 26-week steroid taper regimen achieved sustained remission at week 52, compared with 29.0% of patients receiving placebo in combination with a 52-week steroid taper regimen (p=0.002).1 Key secondary endpoints included: Reduction in disease flares: 34.3% of patients receiving RINVOQ 15 mg in combination with a 26-week steroid taper regimen experienced at least one disease flare through week 52 versus 55.6% of patients receiving placebo in combination with a 52-week steroid taper regimen (p=0.001).1 Lower cumulative steroid exposure: Through 52 weeks, cumulative steroid exposure was significantly lower for patients receiving RINVOQ 15 mg in combination with a 26-week steroid taper regimen than for patients receiving placebo in combination with a 52-week steroid taper regimen (median exposure of 1615 mg versus 2882 mg, respectively; p<0.001).1 Sustained complete remission†: 37.1% of patients receiving RINVOQ 15 mg in combination with a 26-week steroid taper regimen achieved sustained complete remission through week 52, compared with 16.1% of patients receiving placebo in combination with a 52-week steroid taper regimen (p<0.001).1 During the 52-week, placebo-controlled period, the safety profile of RINVOQ was generally consistent with that observed in other approved indications.2 Similar rates of serious adverse events were observed in patients receiving RINVOQ 15 mg and in those receiving placebo.1 Serious infections occurred in 5.7% of the RINVOQ 15 mg group and 10.7% of the placebo group.1 The proportions of patients with events of interest were balanced across treatment groups for incidence of malignancy (excluding nonmelanoma skin cancer; 1.9% in the RINVOQ 15 mg group vs 1.8% in the placebo group) and venous thromboembolism (3.3% in the RINVOQ 15 mg group vs 3.6% in the placebo group).1 There were no adjudicated major adverse cardiac events (MACEs) in the RINVOQ 15 mg group, compared with two events in the placebo group.1 Four treatment-emergent deaths were reported, two in the placebo group and two in the RINVOQ 15 mg group. Of the two treatment-emergent deaths in the RINVOQ 15 mg group, one was attributed to COVID-19 and the other was adjudicated as an unexplained cause.1 RINVOQ is approved in the EU for the treatment of adults with radiographic axial spondylarthritis, nonradiographic axial spondylarthritis, psoriatic arthritis, rheumatoid arthritis, ulcerative colitis, Crohn's disease, adults and adolescents with atopic dermatitis, and now adults with GCA.2 *Sustained remission is defined as having an absence of GCA signs and symptoms from week 12 through week 52 and adherence to the protocol-defined steroid taper over the course of the study term.1†Sustained complete remission is defined as having an absence of GCA signs and symptoms from week 12 through week 52, adherence to the protocol-defined steroid taper, and normalization of both erythrocyte sedimentation rate and high-sensitivity C-reactive protein from week 12 through week 52.1 About Giant Cell ArteritisGiant cell arteritis (GCA), also known as temporal arteritis, is an autoimmune disease of medium and large arteries, characterized by granulomatous inflammation of the three-layered vessel wall, which affects temporal and other cranial arteries as well as the aorta and other large arteries.3,5 GCA can cause headache, jaw pain, and changes in or loss of vision, including sudden and permanent loss of vision.3 It is the most common vasculitis affecting adults in western countries.3 White women over the age of 50 – most commonly between the ages of 70 and 80 years – have the highest risk of developing GCA. Although women are more likely than men to develop GCA, research suggests that men are more likely to have ocular manifestations with their disease.6 About SELECT-GCA SELECT-GCA (M16-852) is a Phase 3, multicenter, randomized, double-blind placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib in 428 patients with GCA. The study consists of two parts. The first part, which is reported in this release, evaluated the efficacy of upadacitinib in combination with a 26-week corticosteroid taper regimen compared with placebo in combination with a 52-week corticosteroid taper regimen. In addition, the study assessed the safety and tolerability of upadacitinib in these patients. The efficacy and safety of withdrawing versus continuing upadacitinib in maintaining remission in participants who achieved sustained remission in the first part will be evaluated in the second part of the study.7 Top-line results of part one of the study were shared in April 2024. For more information regarding this study, please visit ClinicalTrials.gov (identifier: NCT03725202). About Upadacitinib (RINVOQ®)Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.2,8 In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK 1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.2 Upadacitinib (RINVOQ) is being studied in Phase 3 clinical trials for alopecia areata, giant cell arteritis, hidradenitis suppurativa, Takayasu arteritis, systemic lupus erythematosus and vitiligo.9-14 EU Indications and Important Safety Information about RINVOQ® (upadacitinib)2Indications Giant cell arteritisRINVOQ is indicated for the treatment of giant cell arteritis (GCA) in adult patients. Rheumatoid arthritisRINVOQ is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) 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. Psoriatic arthritisRINVOQ is indicated 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. RINVOQ may be used as monotherapy or in combination with methotrexate. Axial spondyloarthritisNon-radiographic axial spondyloarthritis (nr-axSpA)RINVOQ is indicated for the treatment of active non-radiographic axial spondyloarthritis in adult patients with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs).Ankylosing spondylitis (AS, radiographic axial spondyloarthritis)RINVOQ is indicated for the treatment of active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy. Atopic dermatitisRINVOQ is indicated for the treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents 12 years and older who are candidates for systemic therapy. Ulcerative colitisRINVOQ is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent. Crohn's diseaseRINVOQ is indicated for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent. Important Safety Information ContraindicationsRINVOQ 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. Special warnings and precautions for useRINVOQ should only be used if no suitable treatment alternatives are available in patients: 65 years of age and older; patients with history of atherosclerotic cardiovascular (CV) disease or other CV risk factors (such as current or past long-time smokers); patients with malignancy risk factors (e.g. current malignancy or history of malignancy) Use in patients 65 years of age and olderConsidering the increased risk of MACE, malignancies, serious infections, and all-cause mortality in patients ≥65 years of age, as observed in a large randomised study of tofacitinib (another JAK inhibitor), RINVOQ should only be used in these patients if no suitable treatment alternatives are available. In patients ≥65 years of age, there is an increased risk of adverse reactions with RINVOQ 30 mg once daily. Consequently, the recommended dose for long-term use in this patient population is 15 mg once daily. Immunosuppressive medicinal productsUse in combination with other potent immunosuppressants is not recommended. Serious infectionsSerious and sometimes fatal infections have been reported in patients receiving RINVOQ. The most frequent serious infections reported included pneumonia and cellulitis. Cases of bacterial meningitis and sepsis have been reported with RINVOQ. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis have been reported. RINVOQ should not be initiated in patients with an active, serious infection, including localized infections. RINVOQ should be interrupted if a patient develops a serious or opportunistic infection until the infection is controlled. A higher rate of serious infections was observed with RINVOQ 30 mg compared to 15 mg. As there is a higher incidence of infections in the elderly and patients with diabetes in general, caution should be used when treating these populations. In patients ≥65 years of age, RINVOQ should only be used if no suitable treatment alternatives are available. TuberculosisPatients should be screened for TB before starting RINVOQ. RINVOQ should not be given to patients with active TB. Anti-TB therapy may be appropriate for select patients in consultation with a physician with expertise in the treatment of TB. Patients should be monitored for the development of signs and symptoms of TB. Viral reactivationViral reactivation, including cases of herpes zoster, was reported in clinical studies. The risk of herpes zoster appears to be higher in Japanese patients treated with RINVOQ. Consider interruption of RINVOQ if the patient develops herpes zoster until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should occur before and during therapy. If hepatitis B virus DNA is detected, a liver specialist should be consulted. VaccinationThe 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 RINVOQ, in agreement with current immunization guidelines. MalignancyLymphoma and other malignancies have been reported in patients receiving JAK inhibitors, including RINVOQ. In a large randomised active controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥ 1 additional CV risk factor, a higher rate of malignancies, particularly lung cancer, lymphoma, and non-melanoma skin cancer (NMSC), was observed with tofacitinib compared to tumour necrosis factor (TNF) inhibitors. A higher rate of malignancies, including NMSC, was observed with RINVOQ 30 mg compared to 15 mg. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. In patients ≥65 years of age, patients who are current or past long-time smokers, or patients with other malignancy risk factors (e.g., current malignancy or history of malignancy), RINVOQ should only be used if no suitable treatment alternatives are available. Hematological abnormalitiesTreatment should not be initiated, or should be temporarily interrupted, in patients with hematological abnormalities observed during routine patient management. Gastrointestinal PerforationsEvents of diverticulitis and gastrointestinal perforations have been reported in clinical trials and from post-marketing sources. RINVOQ should be used with caution in patients who may be at risk for gastrointestinal perforation (e.g., patients with diverticular disease, a history of diverticulitis, or who are taking nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, or opioids). Patients with active Crohn's disease are at increased risk for developing intestinal perforation. Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis or gastrointestinal perforation. Major adverse cardiovascular eventsMACE were observed in clinical studies of RINVOQ. In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥1 additional CV risk factor, a higher rate of MACE, defined as CV death, non-fatal myocardial infarction and non-fatal stroke, was observed with tofacitinib compared to TNF inhibitors. Therefore, in patients ≥65 years of age, patients who are current or past long-time smokers, and patients with history of atherosclerotic CV disease or other CV risk factors, RINVOQ should only be used if no suitable treatment alternatives are available. LipidsRINVOQ treatment was associated with dose-dependent increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hepatic transaminase elevationsTreatment with RINVOQ was associated with an increased incidence of liver enzyme elevation. Hepatic transaminases must be evaluated at baseline and thereafter according to routine patient management. If alanine transaminase (ALT) or aspartate transaminase (AST) increases are observed and drug-induced liver injury is suspected, RINVOQ should be interrupted until this diagnosis is excluded. Venous thromboembolismEvents of deep venous thrombosis (DVT) and pulmonary embolism (PE) were observed in clinical trials for RINVOQ. In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥1 additional CV risk factor, a dose dependent higher rate of VTE including DVT and PE was observed with tofacitinib compared to TNF inhibitors. In patients with CV or malignancy risk factors, RINVOQ should only be used if no suitable treatment alternatives are available. In patients with known VTE risk factors other than CV or malignancy risk factors (e.g. previous VTE, patients undergoing major surgery, immobilisation, use of combined hormonal contraceptives or hormone replacement therapy, and inherited coagulation disorder), RINVOQ should be used with caution. Patients should be re-evaluated periodically to assess for changes in VTE risk. Promptly evaluate patients with signs and symptoms of VTE and discontinue RINVOQ in patients with suspected VTE. Hypersensitivity reactionsSerious hypersensitivity reactions such as anaphylaxis and angioedema have been reported in patients receiving RINVOQ. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy. Hypoglycemia in patients treated for diabetesThere have been reports of hypoglycemia following initiation of JAK inhibitors, including RINVOQ, in patients receiving medication for diabetes. Dose adjustment of anti-diabetic medication may be necessary in the event that hypoglycemia occurs. Medication Residue in StoolReports of medication residue in stool or ostomy output have occurred in patients taking RINVOQ. Most reports described anatomic (e.g., ileostomy, colostomy, intestinal resection) or functional gastrointestinal conditions with shortened gastrointestinal transit times. Patients should be instructed to contact their healthcare professional if medication residue is observed repeatedly. Patients should be clinically monitored, and alternative treatment should be considered if there is an inadequate therapeutic response. Giant Cell ArteritisRINVOQ monotherapy should not be used for the treatment of acute relapses as efficacy in this setting has not been established. Glucocorticoids should be given according to medical judgement and practice guidelines. Adverse reactionsThe most commonly reported adverse reactions in RA, PsA, and axSpA clinical trials (≥2% of patients in at least one of the indications) with RINVOQ 15 mg were upper respiratory tract infections, blood creatine phosphokinase (CPK) increased, ALT increased, bronchitis, nausea, neutropenia, cough, AST increased, and hypercholesterolemia. Overall, the safety profile observed in patients with psoriatic arthritis or active axial spondyloarthritis treated with RINVOQ 15 mg was consistent with the safety profile observed in patients with RA. The most commonly reported adverse reactions in AD trials (≥2% of patients) with RINVOQ 15 mg or 30 mg were upper respiratory tract infection, acne, herpes simplex, headache, blood CPK increased, cough, folliculitis, abdominal pain, nausea, neutropenia, pyrexia, and influenza. Dose dependent increased risks of infection and herpes zoster were observed with RINVOQ. The safety profile for RINVOQ 15 mg in adolescents was similar to that in adults. With long-term exposure, skin papilloma was reported in adolescents in the RINVOQ 15 mg and 30 mg groups. The most commonly reported adverse reactions in the UC and CD trials (≥3% of patients) with RINVOQ 45 mg, 30 mg or 15 mg were upper respiratory tract infection, pyrexia, blood CPK increased, anemia, headache, acne, herpes zoster, neutropenia, rash, pneumonia, hypercholesterolemia, bronchitis, AST increased, fatigue, folliculitis, ALT increased, herpes simplex, and influenza. The overall safety profile observed in patients with UC was generally consistent with that observed in patients with RA. Overall, the safety profile observed in patients with CD treated with RINVOQ was consistent with the known safety profile for RINVOQ. The most common serious adverse reactions were serious infections. The safety profile of RINVOQ with long-term treatment was generally similar to the safety profile during the placebo-controlled period across indications. Overall, the safety profile observed in patients with GCA treated with RINVOQ 15 mg was generally consistent with the known safety profile for RINVOQ. This is not a complete summary of all safety information. See RINVOQ full Summary of Product Characteristics (SmPC) 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. Anchored by a longstanding commitment to discovering and delivering transformative therapies, we pursue cutting-edge science that improves our understanding of promising new pathways and targets, ultimately helping more people living with rheumatic diseases reach their treatment goals. For more information, visit AbbVie in rheumatology. About AbbVie AbbVie's mission is to discover and deliver innovative medicines and solutions 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 including immunology, oncology, neuroscience and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube. 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 and uses of future or conditional verbs, 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 expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, 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 2024 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, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. References Blockmans D, Penn SK, Setty AR, et al. A phase 3 trial of upadacitinib for giant-cell arteritis. N Engl J Med. Published online April 2, 2025; doi:10.1056/NEJMoa2413449. RINVOQ. Summary of Product Characteristics. AbbVie; 2025. Ameer MA, Peterfy RJ, Khazaeni B. Giant cell arteritis (temporal arteritis). Updated August 8, 2023. https://www.ncbi.nlm.nih.gov/books/NBK459376/ Mohammad AJ, Englund M, Turesson C, et al. Rate of Comorbidities in Giant Cell Arteritis: A Population-based Study. J Rheumatol. 2017;44(1):84-90. doi:10.3899/jrheum.160249 Weyand CM, Goronzy JJ. Immunology of giant cell arteritis. Circ Res. 2023;132(2):238-250. doi:10.1161/CIRCRESAHA.122.322128 Giant cell arteritis. Arthritis Foundation. Accessed January 9, 2025. https://www.arthritis.org/diseases/giant-cell-arteritis AbbVie. Data on file: ABVRRTI78418. Pipeline. AbbVie. 2023. Accessed January 9, 2025. https://www.abbvie.com/our-science/pipeline.html A study to evaluate the safety and efficacy of upadacitinib in participants with giant cell arteritis (SELECT-GCA). ClinicalTrials.gov identifier: NCT03725202. Accessed January 9, 2025. https://clinicaltrials.gov/ct2/show/NCT03725202 A study to evaluate the efficacy and safety of upadacitinib in participants with Takaysu arteritis (TAK) (SELECT-TAK). ClinicalTrials.gov identifier: NCT04161898. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT04161898 Program to assess adverse events and change in disease activity of oral upadacitinib in adult participants with moderate to severe systemic lupus erythematosus (SELECT-SLE). ClinicalTrials.gov identifier: NCT05843643. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT05843643 A study to assess change in disease activity and adverse events of oral upadacitinib in adult and adolescent participants with moderate to severe hidradenitis suppurativa who have failed anti-TNF therapy (Step-Up HS). ClinicalTrials.gov identifier: NCT05889182. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT05889182 A study to assess adverse events and effectiveness of upadacitinib oral tablets in adult and adolescent participants with vitiligo (Viti-Up). ClinicalTrials.gov identifier: NCT06118411. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT06118411 A study to evaluate the safety and effectiveness of upadacitinib tablets in adult and adolescent participants with severe alopecia areata (UP-AA). ClinicalTrials.gov identifier: NCT06012240. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT06012240 SOURCE AbbVie WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In

AbbVie Announces European Commission Approval of RINVOQ® (upadacitinib) for the Treatment of Adults with Giant Cell Arteritis

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