AbbVie Receives Positive CHMP Opinion for Upadacitinib (RINVOQ®) for the Treatment of Adults with Moderate to Severe Crohn's Disease
AbbVie announced a positive recommendation from the European Medicines Agency's CHMP for upadacitinib (RINVOQ) to treat adults with moderately to severely active Crohn's disease. This recommendation is based on results from two induction studies and one maintenance study, which showed significant improvements in clinical remission and endoscopic response compared to placebo. If approved by the European Commission, this will be the seventh indication for upadacitinib in the EU and the first JAK inhibitor for Crohn's disease. Upadacitinib's safety profile was consistent with previous findings, with no new significant risks identified.
- CHMP's positive opinion for upadacitinib bolsters AbbVie's gastroenterology portfolio.
- Upadacitinib demonstrated significant clinical remission and endoscopic response in studies.
- None.
- The positive CHMP opinion for upadacitinib is based on results from two induction studies and one maintenance study1-4
- Crohn's disease is a chronic, systemic disease that manifests as inflammation within the gastrointestinal tract, causing persistent diarrhea and abdominal pain5,6
- If approved by the
European Commission (EC), this will be the seventh indication for upadacitinib in theEuropean Union (EU), and the first JAK inhibitor for Crohn's disease, adding to AbbVie's gastroenterology portfolio
"The recent CHMP recommendation to approve upadacitinib for use in Crohn's disease is a momentous step, bringing us closer to offering a first-of-its-kind, once-daily oral treatment that can make a difference for people living with this disease," said Roopal Thakkar, M.D., senior vice president, development, regulatory affairs and chief medical officer, AbbVie. "We remain steadfast in our commitment to researching and developing treatment options as part of a diverse portfolio of therapies for those living with inflammatory bowel diseases."
AbbVie's application for the approval of upadacitinib in Crohn's disease is supported by data from two induction studies, U-EXCEED and U-EXCEL, and one maintenance study, U-ENDURE.1 Patients receiving upadacitinib were treated with 45 mg once daily for the induction studies, and were randomized to receive either 15 mg or 30 mg once-daily doses for the maintenance study.1-4 Across all three Phase 3 studies, a significantly greater proportion of patients treated with upadacitinib achieved the co-primary endpoints of clinical remission per SF/AP (defined as average daily stool frequency [SF] ≤2.8 and abdominal pain [AP] score ≤1.0 and neither greater than baseline) and endoscopic response (defined as decrease in simple endoscopic score for Crohn's disease [SES-CD] >
In all three studies, a statistically significant greater proportion of patients treated with upadacitinib achieved the key secondary endpoint of endoscopic remission (defined as SES-CD ≤4 and at least a 2-point reduction vs. baseline and no subscore >1). Additionally, more upadacitinib-treated patients achieved SES-CD ulcerated surface subscore of 0 at weeks 12 and 52 (nominal p-value<0.001) in patients with SES-CD ulcerated surface subscore ≥1 at baseline.1-4,* Absence or disappearance of ulceration coupled with improvements seen by endoscopy are associated with mucosal healing.7-10
The safety profile of upadacitinib in Crohn's disease was generally consistent with the known safety profile of upadacitinib.1-4 Similar rates of serious adverse events including serious infections were observed between patients receiving upadacitinib and placebo. Reports of malignancy, major cardiovascular events, venous thromboembolic events and gastrointestinal perforation were infrequently observed (<1.0 Events/100 Patient-Years).
"The impact of Crohn's disease extends beyond the gut to include systemic symptoms such as fatigue, bowel symptoms and social and emotional functioning. Treatment options that achieve critical endpoints such as clinical remission and endoscopic response can make a difference in managing the challenging symptoms of this condition and health-related outcomes related to quality of life," said Jean-Frédéric Colombel, M.D., professor of medicine and director of Inflammatory Bowel Disease Center,
RINVOQ is approved in the EU for the treatment of adults with radiographic axial spondylarthritis, non-radiographic axial spondylarthritis, psoriatic arthritis, rheumatoid arthritis, moderately to severely active ulcerative colitis and adults and adolescents with atopic dermatitis.1,11-15
Use of upadacitinib in Crohn's disease is approved in
About Crohn's Disease
Crohn's disease is a chronic, systemic disease that manifests as inflammation within the gastrointestinal tract, causing persistent diarrhea and abdominal pain.5,6 It is a progressive disease, meaning it gets worse over time in a substantial proportion of patients or may develop complications that require urgent medical care, including surgery.5,6 Because the signs and symptoms of Crohn's disease are unpredictable, it causes a significant burden on people living with the disease—not only physically, but also emotionally and economically.5,6
About the U-EXCEED and U-EXCEL Inductions Studies, and the U-ENDURE Maintenance Study 1-4
The three Phase 3 studies are multicenter, randomized, double-blind, placebo-controlled studies to evaluate the efficacy and safety of upadacitinib 45 mg as induction therapy and upadacitinib 15 mg and 30 mg as maintenance therapy in patients with moderately to severely active Crohn's disease. Topline results of the U-EXCEED and U-EXCEL induction studies were announced in December 2021 and
About Upadacitinib (RINVOQ®)
Discovered and developed by AbbVie scientists, upadacitinib (RINVOQ) is a selective and reversible Janus Kinase (JAK) inhibitor.1 In human cellular assays, upadacitinib preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.1
Phase 3 trials of RINVOQ in Crohn's disease, giant cell arteritis and Takayasu arteritis are ongoing.1,16-18
EU Indications and Important Safety Information about Upadacitinib (RINVOQ®)1
Indications
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.
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.
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.
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 upadacitinib. Upadacitinib 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 the 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.
Hypersensitivity reactions
Serious hypersensitivity reactions such as anaphylaxis and angioedema have been reported in patients receiving upadacitinib. If a clinically significant hypersensitivity reaction occurs, discontinue upadacitinib and institute appropriate therapy.
Adverse reactions
The most commonly reported adverse reactions in RA, PsA, and axSpA clinical trials (≥
The most commonly reported adverse reactions in atopic dermatitis trials (≥
The most commonly reported adverse reactions in UC trials (≥
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 www.ema.europa.eu
Globally, prescribing information varies; refer to the individual country product label for complete information.
About AbbVie in Gastroenterology
With a robust clinical trial program, AbbVie is committed to cutting-edge research to drive exciting developments in inflammatory bowel diseases (IBD), like ulcerative colitis and Crohn's disease. By innovating, learning and adapting, AbbVie aspires to eliminate the burden of IBD and make a positive long-term impact on the lives of people with IBD. For more information on AbbVie in gastroenterology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/gastroenterology.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 our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram.
Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, 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
References:
Abbvie, Ltd. RINVOQ (upadacitinib) [summary of product characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf. Accessed onDecember 7, 2022 .- Colombel, J.F., Panes, J., Lacerda, A.P., et al. Efficacy and Safety of Upadacitinib Induction Therapy in Patients with Moderately to Severely Active Crohn's Disease Who Failed Prior Biologics: Results from a Randomized Phase 3 U-EXCEED Study.
UEG Journal . 2022;S-1934. Accessed onDecember 12, 2022 . - Loftus, E., Colombel, L.F., Lacerda, A.P., et al. Efficacy and Safety of Upadacitinib Induction Therapy in Patients with Moderately to Severely Active Crohn's Disease: Results from a Randomized Phase 3 U-EXCEL Study.
UEG Journal . 2022; 10(8): 103-104. doi/10.1002/ueg2.12293. Accessed onDecember 12, 2022 . - Panes, J., Loftus, E., Lacerda, A.P., et al. Efficacy and Safety of Upadacitinib Maintenance Therapy in Patients with Moderately to Severely Active Crohn's Disease: Results from a Randomized Phase 3 U-ENDURE Maintenance Study.
American College of Gastroenterology . 2022: 1-14. Accessed onDecember 12, 2022 . - Crohn's disease. Symptoms and Causes.
Mayo Clinic . Available at: https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304. Accessed onDecember 7, 2022 . - The Facts about Inflammatory Bowel Diseases.
Crohn's & Colitis Foundation of America . 2014. Available at: https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf. Accessed onDecember 7, 2022 . - Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on the selecting therapeutic targets in inflammatory bowel disease (STRIDE) initiative of the
International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021;160(5):1570-1583. doi:10.1053/j.gastro.2020.12.031. - Dave M, Loftus EV. Mucosal healing in inflammatory bowel disease—a true paradigm of success? Gastroenterol Hepatol. 2012;8(1):29-38.
- Daperno M, Castiglione F, de Ridder L, et al. Results of the 2nd part
Scientific Workshop of the ECCO. II: Measures and markers of prediction to achieve, detect, and monitor intestinal healing in inflammatory bowel disease. J Crohns Colitis. 2011;5(5):484-498. doi:10.1016/j.crohns.2011.07.003. European Medicines Agency . Guideline on the Development of New Medicinal Products for the Treatment of Ulcerative Colitis.EMA Committee for Medicinal Products for Human Use (CHMP); 2018:18. AccessedFebruary 20, 2022 . https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-development-new-medicinal-products-treatment-ulcerative-colitis-revision-1_en.pdf.Guttman-Yassky E , Teixeira HD, Simpson EL, 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, randomised controlled phase 3 trials.The Lancet . 2021;397(10290):2151-2168. doi:10.1016/S0140-6736(21)00588-2- Cohen SB, van Vollenhoven RF, Winthrop KL, et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. Published online
October 28 , 2020:annrheumdis-2020-218510. doi:10.1136/annrheumdis-2020-218510 van der Heijde D , Song IH, Pangan AL, et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial.Lancet . 2019;394(10214):2108-2117. doi:10.1016/S0140-6736(19)32534-6- Mease PJ, Lertratanakul A, Anderson JK, et al. Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. Annals of the Rheumatic Diseases. 2021;80(3):312-320. doi:10.1136/annrheumdis-2020-218870
- Danese, S, Vermeire, S, Zhou, W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials.
The Lancet . 2022;399(10341):2113-2128. doi: 10.1016/S0140-6736(22)00581-5. - Pipeline – Our Science | AbbVie. AbbVie. 2022. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on December 7, 2022.
- A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed on December 7, 2022.
- A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (TAK) (SELECT-TAK). ClinicalTrials.gov. 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT04161898. Accessed on December 7, 2022.
* Mucosal healing was a prespecified endpoint, not controlled for multiplicity.
View original content:https://www.prnewswire.com/news-releases/abbvie-receives-positive-chmp-opinion-for-upadacitinib-rinvoq-for-the-treatment-of-adults-with-moderate-to-severe-crohns-disease-301756139.html
SOURCE AbbVie
FAQ
What is the significance of the CHMP's positive opinion for ABBV stock?
When will the European Commission make a decision on upadacitinib?
How does upadacitinib work for Crohn's disease?
What previous approvals does upadacitinib have?
What were the results of the Phase 3 studies for upadacitinib?