HyperCKmia

- Study Did Not Meet Primary or Secondary Efficacy Endpoints in Hidradenitis Suppurativa - Overall Safety Pro PK/PD Generally Consistent with Observations in Prior Studies of Zunsemetinib WAYNE, Pa., March 06, 2023 (GLOBE NEWSWIRE) -- Aclaris Therapeutics Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, today announced preliminary topline results from a 12-week, Phase 2a, multicenter, randomized, placebo-controlled clinical study to investigate the efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of zunsemetinib (ATI-450), an investigational oral MK2 inhibitor, in patients with moderate to severe hidradenitis suppurativa (HS) (ATI-450-HS-201). Efficacy The study did not meet its primary endpoint of change from baseline in inflammatory nodule/abscess count (AN) of zunsemetinib 50mg BID versus placebo at week 12. The study also did not meet the secondary efficacy endpoints assessed in the topline data, including percentage of patients achieving HiSCR-50. The placebo effect observed across all efficacy endpoints was higher than what has been observed in other published HS studies reported to date. Safety Zunsemetinib was generally well tolerated. Safety findings were generally consistent with observations from prior clinical studies of zunsemetinib. The most common treatment-emergent adverse events in patients treated with zunsemetinib were dizziness (16.7%), diarrhea (12.5%), headache (12.5%), creatine phosphokinase (CPK) elevation (10.4%) and acne (10.4%), with a majority deemed mild to moderate in severity. Dizziness, diarrhea, headache and CPK elevation were generally transient in nature. Thirty-seven patients discontinued study treatment (22 on zunsemetinib and 15 on placebo), with 15 patients discontinuing treatment due to AEs (11 on zunsemetinib and 4 on placebo). No serious adverse events and no serious and/or opportunistic infections were observed with patients treated with zunsemetinib. Pharmacokinetics/Pharmacodynamics PK and PD were generally consistent with observations from prior clinical studies of zunsemetinib. A preliminary analysis of endogenous plasma cytokines and chemokines in patients with a confirmed dose of study treatment on the day of blood draw, demonstrated zunsemetinib dependent inhibition relative to placebo. Of the proinflammatory markers that were elevated at baseline relative to healthy donors, including IL6, IL8 and MIP1b, treatment-related median inhibition trends were observed across the 12-week dosing period. While the proinflammatory cytokine IL12/23p40 was not elevated at baseline relative to healthy donors, a median inhibition trend was observed in patients treated with zunsemetinib. In the subset of patients with quantifiable IL17A/F levels at baseline, the cytokine was elevated relative to healthy donors and an inhibition trend was observed with zunsemetinib treatment. Endogenous TNFα plasma levels were not elevated relative to healthy donors yet a small inhibition trend was observed in treated patients. The anti-inflammatory cytokine IL1RA was elevated at baseline and treatment-related inhibition was not observed. “We are incredibly grateful to the patients, investigators, our internal study team and all others who contributed to the execution of this clinical trial,” stated Doug Manion, M.D. Aclaris’ Chief Executive Officer. “Despite not producing the efficacy results we had hoped for in this particularly challenging disease, we are encouraged by the consistent demonstration of zunsemetinib’s mechanism of action and the strengthening of our safety data base and continue to look forward to our next data read out of our Phase 2b study of zunsemetinib in patients with moderate to severe rheumatoid arthritis.” About ATI-450-HS-201 Phase 2a Study (NCT05216224) ATI-450-HS-201 is a randomized, double-blind, placebo-controlled, multi-center Phase 2a study to investigate the efficacy, safety, tolerability, PK and PD of zunsemetinib (50 mg twice daily) in patients with moderate to severe HS. The study enrolled 95 patients who were randomized 1:1 to zunsemetinib (n=48) or placebo (n=47) across 19 clinical study sites in the US. The primary endpoint of the study is change from baseline in inflammatory nodule/abscess count at week 12. The topline efficacy analyses are based on the full analysis set. Healthy volunteer samples for PD analyses were obtained outside of the clinical trial setting. About Zunsemetinib (ATI-450) Zunsemetinib is an investigational oral mitogen-activated protein kinase-activated protein kinase 2 (MK2) inhibitor. This mechanism potentially leads to the inhibition of multiple cytokines, chemokines, matrix metalloproteases and other inflammatory signals. Key inflammatory cytokines driven by this mechanism include TNFα and interleukin-1α, -1β, -6, -8 and -17 (IL1α, IL1β, IL6, IL8 and IL17). Aclaris is developing zunsemetinib as a potential treatment for rheumatoid arthritis and psoriatic arthritis. About Aclaris Therapeutics, Inc. Aclaris Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates to address the needs of patients with immuno-inflammatory diseases who lack satisfactory treatment options. The company has a multi-stage portfolio of drug candidates powered by a robust R&D engine exploring protein kinase regulation. For additional information, please visit . Cautionary Note Regarding Forward-Looking Statements Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “believe,” “expect,” “intend,” “may,” “plan,” “potential,” “will,” and similar expressions, and are based on Aclaris’ current beliefs and expectations. These forward-looking statements include Aclaris’ expectations regarding the timing of reporting results from its clinical studies. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the conduct of clinical trials, Aclaris’ reliance on third parties over which it may not always have full control, Aclaris’ ability to enter into strategic partnerships on commercially reasonable terms, the uncertainty regarding the macroeconomic environment and the COVID-19 pandemic and other risks and uncertainties that are described in the Risk Factors section of Aclaris’ Annual Report on Form 10-K for the year ended December 31, 2022 and other filings Aclaris makes with the U.S. Securities and Exchange Commission from time to time. These documents are available under the “SEC Filings” page of the “Investors” section of Aclaris’ website at Any forward-looking statements speak only as of the date of this press release and are based on information available to Aclaris as of the date of this release, and Aclaris assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise. Aclaris Therapeutics Contact: Robert A. Doody Jr. Vice President, Investor Relations 484-639-7235 rdoody@aclaristx.com

With this approval, RINVOQ® (upadacitinib 15 mg, once daily) is the first and only Janus Kinase (JAK) inhibitor approved to treat patients across the spectrum of axial spondyloarthritis (nr-axSpA and ankylosing spondylitis) in the European Union (EU)1 Approval is supported by data from the Phase 3 SELECT-AXIS 2 pivotal clinical trial in which RINVOQ delivered meaningful disease control with nearly half of nr-axSpA patients achieving ASAS40 at week 14 (45 percent versus 23 percent; p<0.0001) compared to placebo2 NORTH CHICAGO, Ill., July 29, 2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the European Commission (EC) has approved RINVOQ® (upadacitinib 15 mg, once daily), an oral therapy, for the treatment of active non-radiographic axial spondyloarthritis (nr-axSpA) 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).*1 "For years, healthcare providers and patients have had limited treatment options to manage axial spondyloarthritis, which can cause back pain, stiffness, and irreversible damage to the spine," said Thomas Hudson, M.D., senior vice president of research and development, chief scientific officer, AbbVie. "AbbVie is proud to offer RINVOQ as a first-in-class treatment option now approved in the European Union for adults living with nr-axSpA with objective signs of inflammation and inadequate response to NSAIDs. RINVOQ is the first and only JAK inhibitor approved to treat patients across the spectrum of axial spondyloarthritis, which includes nr-axSpA and ankylosing spondylitis." Axial spondyloarthritis (axSpA) is a chronic, progressive and disabling inflammatory rheumatic disease that causes joint inflammation, leading to back pain and stiffness.3,4,5 AxSpA consists of two subsets that have been clinically defined as ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis (r-axSpA), and non-radiographic axial spondyloarthritis (nr-axSpA).6 Approximately 10-40 percent of patients eventually progress from nr-axSpA to r-axSpA over a 2- to 10-year period.7 "The European Commission's approval of RINVOQ for the treatment of nr-axSpA offers physicians in the European Union an important new therapeutic option with proven efficacy in both nr-axSpA and AS patient populations," said Filip Van den Bosch, M.D.,** SELECT-AXIS 2 investigator and professor in the Department of Rheumatology at the University Hospital of Ghent University. "Living with nr-axSpA can pose many challenges and significantly impact a patient's quality of life. Early and effective disease management of patients with active nr-axSpA is key to improving health outcomes." AbbVie previously disclosed topline results from the Phase 3 SELECT-AXIS 2 nr-axSpA clinical trial and the full results have been published in The Lancet. Study results show a significantly greater proportion of patients receiving RINVOQ 15 mg achieved an Assessment of SpondyloArthritis international Society 40 percent (ASAS40) response at week 14 (45 percent versus 23 percent; p<0.0001) compared to placebo.2 Statistical significance was also achieved in 12 of the 14 multiplicity-controlled secondary endpoints compared to placebo at week 14.2 Safety data were previously reported with no new risks identified compared to the known safety profile of RINVOQ.2 Through week 14, the proportion of patients who experienced an adverse event (AE) was similar between treatment groups (RINVOQ at 48 percent and placebo at 46 percent).2 The EC Marketing Authorization for nr-axSpA means that RINVOQ is approved in all member states of the European Union, as well as Iceland, Liechtenstein, Northern Ireland and Norway. RINVOQ also recently received a label enhancement in the EU for the already approved indication of AS to include data on patients with active AS who had an inadequate response to biologic disease-modifying anti-rheumatic drugs (bDMARDs) based on the results of the Phase 3 SELECT-AXIS 2 clinical trial in this population, as well as two-year results of the Phase 2/3 SELECT-AXIS 1 clinical trial that evaluated AS bDMARD-naïve patients.8,9 AbbVie previously disclosed topline results from the Phase 3 SELECT-AXIS 2 AS bDMARD-IR study, in which a significantly greater proportion of patients receiving RINVOQ 15 mg achieved an ASAS40 response at week 14 (45 percent versus 18 percent) compared to placebo.8 All 14 ranked secondary endpoints were met including those evaluating improvements from baseline in disease activity, pain (total and nocturnal back pain), function, MRI SPARCC score (spine), spinal mobility, enthesitis, and health-related quality of life.8 Safety data were previously reported with no new risks identified compared to the known safety profile of RINVOQ.8 Through week 14, the proportion of patients who experienced an AE was similar between treatment groups (RINVOQ at 41 percent and placebo at 37 percent).8 About the SELECT-AXIS 1 and SELECT-AXIS 2 trial programs2, 8 , 9 SELECT-AXIS 1 is a Phase 2/3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the safety and efficacy of RINVOQ in adult patients with active AS who are bDMARD-naïve and had inadequate response to at least two NSAIDs or intolerance to/contraindication for NSAIDs. Period 2 is an open-label extension period to evaluate the long-term safety and efficacy of RINVOQ in subjects who completed Period 1. More information on this trial can be found at (2017-000431-14) in the EU, and at (NCT03178487) in the U.S. SELECT-AXIS 2 (NCT04169373) was conducted under a master protocol and includes two separate studies (SELECT-AXIS 2 AS (bDMARD-IR) study, or Study 1 and SELECT-AXIS 2 nr-axSpA study, or Study 2). Study 1: SELECT-AXIS 2 AS (bDMARD-IR) study8 A randomized, double-blind, placebo-controlled Phase 3 trial, which evaluated the efficacy and safety of RINVOQ compared with placebo, in 420 patients with a clinical diagnosis of AS who fulfilled the modified New York criteria, had BASDAI score ≥4 and total back pain score ≥4 (based on a numerical scale of 0-10), and had an inadequate response to bDMARD therapy. Study 2: SELECT-AXIS 2 nr-axSpA study2 A randomized, double-blind, placebo-controlled, Phase 3 trial which evaluated the efficacy and safety of RINVOQ compared with placebo, in 314 patients with a clinical diagnosis of nr-axSpA. Patients enrolled in the study had active signs of inflammation as indicated by MRI + sacroiliac joint inflammation, and/or high sensitivity C-reactive protein (hs-CRP) >upper limit of normal (2.87 mg/L) at screening, and who had BASDAI score ≥4 and a total back pain score ≥4 (based on a numerical scale of 0-10). More information on the SELECT-AXIS 2 program is available at (2019-003229-12) in the EU, and at (NCT04169373) in the U.S. About Axial Spondyloarthritis (axSpA) Axial spondyloarthritis is a chronic inflammatory disease that affects the spine, causing back pain, limited mobility, and structural damage.6 It consists of two subsets that have been clinically defined as radiographic axial SpA (ankylosing spondylitis) and non-radiographic axial spondyloarthritis (nr-axSpA).6 In ankylosing spondylitis, patients have definitive structural damage of the sacroiliac joints visible on X-rays. Non-radiographic axial spondyloarthritis is clinically defined by the absence of definitive X-ray evidence of structural damage to the sacroiliac (SI) joint by plain X-ray.6 About RINVOQ ® (upadacitinib) 1 Discovered and developed by AbbVie scientists, RINVOQ is a selective JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. 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. In the EU, RINVOQ is approved for the treatment of adults 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; 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; for the treatment of active non-radiographic axial spondyloarthritis in adult patients with objective signs of inflammation as indicated by elevated CRP and/or MRI, who have responded inadequately to NSAIDs; for the treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy; for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate to severe atopic dermatitis; and 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.1 Phase 3 trials of RINVOQ in atopic dermatitis, axial spondyloarthritis, Crohn's disease, giant cell arteritis and Takayasu arteritis are ongoing.10,11,12,13,14,15 EU Indications and Important Safety Information about RINVOQ® (upadacitinib)1 Indications Ulcerative colitis RINVOQ 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. Rheumatoid arthritis RINVOQ 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 arthritis RINVOQ 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 spondyloarthritis Non-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 dermatitis RINVOQ 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. Important Safety Information Contraindications 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. Special warnings and precautions for use Immunosuppressive medicinal products Use in combination with other potent immunosuppressants is not recommended. Serious infections 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/esophageal candidiasis, and cryptococcosis have been reported with upadacitinib. As there is a higher incidence of infections in patients ≥65 years of age, caution should be used when treating this population. Upadacitinib should be interrupted if a patient develops a serious or opportunistic infection. Tuberculosis Patients 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 reactivation Viral 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 upadacitinib. Consider interruption of upadacitinib if patient develops herpes zoster. Vaccinations 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. Malignancy The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Malignancies, including nonmelanoma 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. Hematological abnormalities Treatment should not be initiated, or should be temporarily interrupted, in patients with hematological abnormalities observed during routine patient management. Diverticulitis Upadacitinib should be used with caution in patients with diverticular disease and especially in patients chronically treated with concomitant medications associated with an increased risk of diverticulitis. Cardiovascular risk RA patients have an increased risk for cardiovascular disorders. Patients treated with upadacitinib should have risk factors (e.g., hypertension, hyperlipidemia) managed as part of usual standard of care. Lipids Upadacitinib treatment was associated with dose-dependent increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hepatic transaminase elevations Treatment with upadacitinib was associated with an increased incidence of liver enzyme elevation. If alanine transaminase (ALT) or aspartate transaminase (AST) increases are observed and drug-induced liver injury is suspected, upadacitinib should be interrupted until this diagnosis is excluded. Venous thromboembolisms 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. If clinical features of DVT/PE occur, upadacitinib should be discontinued and patients should be evaluated and treated appropriately. Elderly There is an increased risk of adverse reactions with the upadacitinib dose of 30 mg once daily in patients aged 65 years and older. The recommended dose for long-term use is 15 mg once daily for this patient population. Adverse reactions The most commonly reported adverse reactions in RA, PsA, and axSpA clinical trials (≥2% of patients in at least one of the indications) with upadacitinib 15 mg were upper respiratory tract infections, blood creatine phosphokinase (CPK) increased, ALT increased, bronchitis, nausea, cough, AST increased, and hypercholesterolemia. Overall, the safety profile observed in patients with psoriatic arthritis or active axial spondyloarthritis treated with upadacitinib 15 mg was consistent with the safety profile observed in patients with RA. The most commonly reported adverse reactions in atopic dermatitis trials (≥2% of patients) with upadacitinib 15 mg or 30 mg were upper respiratory tract infection, acne, herpes simplex, headache, CPK increased, cough, folliculitis, abdominal pain, nausea, neutropenia, pyrexia, and influenza. Dose-dependent increased risks of infection and herpes zoster were observed with upadacitinib. The safety profile for upadacitinib 15 mg in adolescents was similar to that in adults. The safety and efficacy of the 30 mg dose in adolescents are still being investigated. The most commonly reported adverse reactions in UC trials (≥3% of patients) with upadacitinib 45 mg, 30 mg or 15 mg were upper respiratory tract infection, blood CPK increased, acne, neutropaenia, rash, herpes zoster, hypercholesterolemia, folliculitis, herpes simplex, and influenza. The overall safety profile observed in patients with ulcerative colitis was generally consistent with that observed in patients with RA. The most common serious adverse reactions were serious infections. The safety profile of upadacitinib with long term treatment was generally similar to the safety profile during the placebo-controlled period across indications. This is not a complete summary of all safety information. See RINVOQ full summary of product characteristics (SmPC) at . 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 . 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 . 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, 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 2021 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. *This recommendation is without prejudice to the final conclusions of the ongoing referral procedure under Article 20 of Regulation (EC) No 726/2004 resulting from pharmacovigilance data. **Dr. Van den Bosch is a consultant and advisor for AbbVie. References: 1 AbbVie, Ltd. RINVOQ (upadacitinib) [summary of product characteristics]. . Accessed July 28, 2022. 2 Deodhar, A, et al. Efficacy and Safety of Upadacitinib in Patients with Active Non-Radiographic Axial Spondyloarthritis: a Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial. EULAR 2022 Congress; 2534. 3 Crossfield SSR, Marzo-Ortega H, Kingsbury SR, et al. Changes in ankylosing spondylitis incidence, prevalence and time to diagnosis over two decades. RMD Open 2021;7:e001888. doi: 10.1136/rmdopen-2021-001888. 4 Mayo Clinic. Ankylosing Spondylitis. 2019. Available at: . Accessed June 2022. 5 Dean, LE, et al. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford). 2014 Apr;53(4):650-7. doi: 10.1093/rheumatology/ket387. Epub 2013 6 Deodhar AA, Understanding Axial Spondyloarthritis: A Primer for Managed Care. Am J Manag Care. 2019;25:S319-S330. 7 Protopopov M, Poddubnyy D. Radiographic progression in non-radiographic axial spondyloarthritis. Expert Rev Clin Immunol. 2018;14(6):525-533. 8 Van der Heijde, D, et al. Efficacy and Safety of Upadacitinib in Patients With Active Ankylosing Spondylitis Refractory to Biologic Therapy: a Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial. EULAR 2022 Congress; 2518. 9 Van der Heijde D, et al. Efficacy and Safety of Upadacitinib in Patients with Active Ankylosing Spondylitis: 2-Year Results from a Randomized, Double-Blind, Placebo-Controlled Study with Open-Label Extension [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10). 10 Evaluation of Upadacitinib in Adolescent and Adult Patients With Moderate to Severe Atopic Dermatitis (Eczema) (Measure Up 1). ClinicalTrials.gov. 2021. Available at: . Accessed June 2022. 11 A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT-AXIS 2). ClinicalTrials.gov. 2021. Available at: . Accessed June 2022. 12 A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Biologic Therapy. ClinicalTrials.gov. 2021. Available at: . Accessed June 2022. 13 A Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UC). ClinicalTrials.gov. 2021. Available at: . Accessed June 2022. 14 A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2021. Available at: . Accessed June 2022. 15 A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (TAK) (SELECT-TAK). ClinicalTrials.gov. 2021. Available at: . Accessed June 2022. SOURCE AbbVie

NORTH CHICAGO, Ill., June 27, 2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended the approval of upadacitinib (RINVOQ® 15 mg, once daily) for the treatment of active non-radiographic axial spondyloarthritis (nr‑axSpA) 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).* "Patients with axSpA often experience delayed diagnosis and once they do receive a diagnosis, there are limited therapies available to help control disease symptoms, such as inflammation, back pain and stiffness," said Neil Gallagher, M.D., Ph.D., vice president, development, chief medical officer, AbbVie. "The CHMP's recommendation to approve upadacitinib for patients with nr-axSpA is an important milestone in providing a new treatment option to patients in need." The CHMP positive opinion is a scientific recommendation for marketing authorization to the European Commission (EC), which will review it and issue a Commission decision that will be valid in all member states of the European Union (EU), as well as Iceland, Liechtenstein, Northern Ireland and Norway. AbbVie's application for the approval of upadacitinib in nr-axSpA is supported by results from the Phase 3 SELECT-AXIS 2 study, for which AbbVie disclosed topline results in 2021. In the Phase 3 clinical study, the SELECT-AXIS 2 nr-axSpA study met the primary endpoint of Assessment of SpondyloArthritis international Society 40 percent response criteria (ASAS40), and the first 12 of 14 ranked secondary endpoints.1 Safety data were previously reported with no new risks identified compared to the known safety profile of upadacitinib.1 Upadacitinib is currently approved for use in the EU in patients with moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderate to severe atopic dermatitis.5 The use of upadacitinib in nr-axSpA is not approved in the U.S. or EU. Its efficacy and safety remain under review. About the SELECT-AXIS 2 program SELECT-AXIS 2 (NCT04169373) was conducted under a master protocol and includes two separate studies (SELECT-AXIS 2 AS (bDMARD-IR) study, or Study 1 and SELECT-AXIS 2 nr-axSpA study, or Study 2). More information on the SELECT-AXIS 2 program is available at https://www.clinicaltrialsregister.eu/ (2019-003229-12) in the EU, and at www.clinicaltrials.gov (NCT04169373) in the U.S. Study 1: SELECT-AXIS 2 AS (bDMARD-IR) study6 A randomized, double-blind, placebo-controlled Phase 3 trial, which evaluated the efficacy and safety of upadacitinib compared with placebo, in 420 patients with a clinical diagnosis of AS who fulfilled the modified New York criteria, had BASDAI score ≥4 and total back pain score ≥4 (based on a numerical scale of 0-10), and had an inadequate response to bDMARD therapy. Study 2: SELECT-AXIS 2 nr-axSpA study1 A randomized, double-blind, placebo-controlled, Phase 3 trial which evaluated the efficacy and safety of upadacitinib compared with placebo, in 314 patients with a clinical diagnosis of nr-axSpA. Patients enrolled in the study had active signs of inflammation as indicated by MRI + sacroiliac joint inflammation, and/or high sensitivity C-reactive protein (hs-CRP) >upper limit of normal (2.87 mg/L) at screening, and who had BASDAI score ≥4 and a total back pain score ≥4 (based on a numerical scale of 0-10). About Axial Spondyloarthritis (axSpA) Axial spondyloarthritis is a chronic inflammatory disease that affects the spine, causing back pain, limited mobility, and structural damage.4 It consists of two subsets that have been clinically defined as radiographic axial SpA (ankylosing spondylitis) and non-radiographic axial spondyloarthritis (nr-axSpA).4 In ankylosing spondylitis, patients have definitive structural damage of the sacroiliac joints visible on X-rays.4 Non-radiographic axial spondyloarthritis is clinically defined by the absence of definitive X-ray evidence of structural damage to the sacroiliac joint by plain X-ray.4 About RINVOQ® (upadacitinib)5 Discovered and developed by AbbVie scientists, RINVOQ is a selective JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.5 In the EU, RINVOQ is approved for the treatment of adults 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; 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; for the treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy; and for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate to severe atopic dermatitis.5 Phase 3 trials of RINVOQ in axial spondyloarthritis, Crohn's disease, giant cell arteritis and Takayasu arteritis are ongoing.7,8,9,10 Use of RINVOQ in nr-axSpA is not approved and remains under review by regulatory authorities. EU Indications and Important Safety Information about RINVOQ® (upadacitinib)5 Indications Rheumatoid arthritis RINVOQ 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. Psoriatic arthritis RINVOQ is indicated for the treatment of active psoriatic arthritis 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. Ankylosing spondylitis RINVOQ is indicated for the treatment of active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy. Atopic dermatitis RINVOQ is indicated for the treatment of moderate to severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy. Important Safety Information Contraindications 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. Special warnings and precautions for use Immunosuppressive medicinal products Use in combination with other potent immunosuppressants is not recommended. Serious infections 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/esophageal candidiasis, and cryptococcosis have been reported with upadacitinib. As there is a higher incidence of infections in patients ≥65 years of age, caution should be used when treating this population. Viral reactivation Viral 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 upadacitinib. Vaccinations 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. Malignancy The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Malignancies, including nonmelanoma 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. Hematological abnormalities Treatment should not be initiated, or should be temporarily interrupted, in patients with hematological abnormalities observed during routine patient management. Diverticulitis Upadacitinib should be used with caution in patients with diverticular disease and especially in patients chronically treated with concomitant medications associated with an increased risk of diverticulitis. Cardiovascular risk RA patients have an increased risk for cardiovascular disorders. Patients treated with upadacitinib should have risk factors (e.g., hypertension, hyperlipidemia) managed as part of usual standard of care. Lipids Upadacitinib treatment was associated with dose-dependent increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hepatic transaminase elevations Treatment with upadacitinib was associated with an increased incidence of liver enzyme elevation compared to placebo. Venous thromboembolisms 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. Adverse reactions The most commonly reported adverse reactions in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis clinical trials (≥2% of patients in at least one of the indications) with upadacitinib 15 mg were upper respiratory tract infections, blood creatine phosphokinase (CPK) increased, alanine transaminase (ALT) increased, bronchitis, nausea, cough, aspartate transaminase (AST) increased, and hypercholesterolemia. The most commonly reported adverse reactions in atopic dermatitis trials (≥2% of patients) with upadacitinib 15 mg or 30 mg were upper respiratory tract infection, acne, herpes simplex, headache, CPK increased, cough, folliculitis, abdominal pain, nausea, neutropenia, pyrexia, and influenza. The most common serious adverse reactions were serious infections. The safety profile of upadacitinib 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 psoriatic arthritis or active ankylosing spondylitis treated with upadacitinib 15 mg was consistent with the safety profile observed in patients with RA. In atopic dermatitis, dose-dependent increased risks of infection and herpes zoster were observed with upadacitinib. Based on limited data, there was a higher rate of overall adverse reactions with the upadacitinib 30 mg dose compared to the 15 mg dose in patients aged 65 years and older. The safety profile for upadacitinib 15 mg in adolescents was similar to that in adults. The safety and efficacy of the 30 mg dose in adolescents are still being investigated. Dose-dependent changes in ALT increased and/or AST increased (≥ 3 x ULN), lipid parameters, CPK values (> 5 x ULN), and neutropenia (ANC 9 cells/L) associated with upadacitinib treatment were similar to what was observed in the rheumatologic disease clinical studies. This is not a complete summary of all safety information. See RINVOQ full summary of product characteristics (SmPC) at www.ema.europa.eu/en. 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.