– Seventh approved indication for RINVOQ in the
European Union (EU) and the first and only oral Janus Kinase (JAK)
inhibitor approved to treat adult patients with moderately to
severely active Crohn's disease
– Third gastroenterology indication approved
across AbbVie's Inflammatory Bowel Disease portfolio in less than a
year
– A significantly higher proportion of patients treated
with RINVOQ achieved the co-primary endpoints of endoscopic
response and clinical remission and the key secondary endpoint of
corticosteroid-free clinical remission at weeks 12 and 52 compared
to placebo1-4; safety results in Crohn's disease were
generally consistent with the known safety profile of
RINVOQ1,5-9
– Crohn's disease is a chronic, systemic disease that
manifests as inflammation within the gastrointestinal tract and is
progressive, potentially producing complications that
require urgent medical care, including
surgery10,11
NORTH
CHICAGO, Ill., April 17,
2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced the European Commission (EC) approved
RINVOQ® (upadacitinib, 45 mg [induction dose] and
15 mg and 30 mg [maintenance doses]) as the first oral Janus Kinase
(JAK) inhibitor 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.1-4
"The EC approval of RINVOQ in Crohn's disease is a significant
milestone in offering patients the first and only once-daily oral
treatment that can provide endoscopic improvement, and sustained
symptom relief, making a difference in their daily lives,"
said Thomas Hudson, M.D., senior vice president, research and
development, chief scientific officer, AbbVie. "With existing
therapies, not all patients are able to achieve adequate disease
control to meet their treatment goals, which is why we continue to
embrace the challenge of expanding our IBD portfolio with new
treatment options."
The EC approval is supported by data from two induction studies,
U-EXCEED and U-EXCEL, and the U-ENDURE maintenance
study.1 Statistical significance was achieved for the
co-primary endpoints and key secondary endpoints with RINVOQ 45 mg
in the induction studies and RINVOQ 15 mg and 30 mg in the
maintenance study compared to placebo.1-4
Co-Primary Endpoint Results from the Phase 3 program
include1-4:
- Endoscopic response*: In U-EXCEED and
U-EXCEL, 35% and 46% of patients treated with RINVOQ 45 mg achieved
endoscopic response at week 12, respectively, compared to 4% and
13% of patients receiving placebo.1 In U-ENDURE, 28% and
40% of patients treated with RINVOQ 15 mg and 30 mg achieved
endoscopic response at week 52, respectively, compared to 7% of
patients receiving placebo.1
- Clinical remission†: In
U-EXCEED and U-EXCEL, 40% and 51% of patients treated with RINVOQ
45 mg achieved clinical remission at 12 weeks, respectively,
compared to 14% and 22% of patients receiving placebo.1
Additionally, in U-ENDURE, 36% and 46% patients treated with RINVOQ
15 mg and 30 mg achieved clinical remission at 52 weeks,
respectively, compared to 14% of patients receiving
placebo.1
Key Secondary and Additional Endpoints include:
- Corticosteroid-free clinical
remission‡: In U-EXCEED and U-EXCEL,
37% and 44% of patients treated with RINVOQ 45 mg achieved
steroid-free remission at week 12, respectively, compared to 7% and
13% of patients receiving placebo. In U-ENDURE, 35% and 45% of
patients treated with RINVOQ 15 mg and 30 mg achieved steroid-free
remission at week 52, respectively, compared to 14% of patients
receiving placebo.1
- Mucosal healing§: Additionally, in
U-EXCEED and U-EXCEL, 17% and 25% of patients treated with RINVOQ
45mg achieved SES-CD ulcerated surface subscore of 0 at week 12,
respectively, compared to 0% and 5% of patients receiving placebo.
In U-ENDURE, 13% and 24% of patients treated with RINVOQ 15 mg and
30 mg achieved SES-CD ulcerated surface subscore of 0 at week 52
compared to 4% of patients receiving placebo (all with nominal
p-value<0.001).1
"Crohn's disease is a burden that can present patients with
daily, often uncomfortable challenges," said Laurent
Peyrin-Biroulet, M.D., Ph.D., professor of gastroenterology and
head of the Inflammatory Bowel Disease group at the
Gastroenterology Department, University Hospital of Nancy,
France. "These studies demonstrated RINVOQ's ability to
achieve key treatment targets, including endoscopic outcomes and
symptomatic relief, that are critical for patients and beneficial
for long-term care."
The safety profile of RINVOQ in Crohn's disease was generally
consistent with the known safety profile of
RINVOQ.1-4 Similar rates of serious adverse events
including serious infections, were observed between patients
receiving RINVOQ and placebo.1-4 The most common adverse
events included nasopharyngitis, acne and COVID-19 in the RINVOQ
treatment group.1-4 Reports of malignancy, major
cardiovascular events, venous thromboembolic events and
gastrointestinal perforation were infrequently observed (<1.0
Events/100 Patient-Years).
RINVOQ is approved in the EU for the treatment of adults with
radiographic axial spondyloarthritis, non-radiographic axial
spondyloarthritis, psoriatic arthritis, rheumatoid arthritis,
ulcerative colitis, adults and adolescents with atopic dermatitis
and now Crohn's disease.1,5-9
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.10,11It 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.10,11 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.10,11
About the U-EXCEED and U-EXCEL Inductions Studies, and the
U-ENDURE Maintenance Study1-4
The three Phase 3
studies are multicenter, randomized, double-blind,
placebo-controlled studies to evaluate the efficacy and safety of
RINVOQ 45 mg as induction therapy and RINVOQ 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 February
2022. Topline results of the U-ENDURE maintenance study were
announced in May 2022. More information can be found
on www.clinicaltrials.gov (U-EXCEED: NCT03345836 ,
U-EXCEL: NCT03345849 , U-ENDURE: NCT03345823).
About RINVOQ® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a
selective and reversible Janus Kinase (JAK) inhibitor.1
In human cellular assays, RINVOQ preferentially inhibits signaling
by JAK1 or JAK1/3 with functional selectivity over cytokine
receptors that signal via pairs of JAK2.1
Phase 3 trials of upadacitinib (RINVOQ) in giant cell arteritis
and Takayasu arteritis are ongoing.1,12-14
EU Indications and Important Safety Information about
RINVOQ®
(upadacitinib)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.
Crohn's disease
RINVOQ 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
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
RINVOQ 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 older
Considering 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 products
Use in combination with other potent immunosuppressants is not
recommended.
Serious infections
Serious 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.
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 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.
Vaccination
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 RINVOQ, in agreement with
current immunization guidelines.
Malignancy
Lymphoma 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 abnormalities
Treatment should not be initiated, or should be temporarily
interrupted, in patients with hematological abnormalities observed
during routine patient management.
Gastrointestinal Perforations
Events 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 events
MACE 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.
Lipids
RINVOQ 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 RINVOQ 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, RINVOQ should be interrupted until this
diagnosis is excluded.
Venous thromboembolism
Events 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 reactions
Serious 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.
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 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. The safety and efficacy of the 30 mg dose in adolescents
are still being investigated.
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, neutropaenia,
rash, pneumonia, hypercholesterolemia, bronchitis, aspartate
transaminase increased, fatigue, folliculitis, alanine transaminase
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 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, 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 2022 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:
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland
GmbH & Co. KG; March 2023.
https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf
- Colombel JF, Panes J, Lacerda AP, Peyrin-Biroulet L. Efficacy
and safety of upadacitinib induction therapy in patients with
moderately to severely active Crohn's disease who failed prior
biologics: results form a randomized phase 3 U-EXCEED study.
Gastroenterology. 2022;162(7):S-1394.
doi:10.1016/S0016-5085(22)64061-7
- Loftus EV, Colombel LF, Lacerda AP, 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. United European Gastroenterol J.
2022;10(8):103-104. doi: 10.1002/ueg2.12293.
- Panes J, Loftus E, Lacerda AP, Peyrin-Biroulet L, D'Haens G,
Panaccione R. 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.
- 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. 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. [published
correction appears in Ann Rheum Dis. 2021 May;80(5):e83]. Ann
Rheum Dis. 2021;80(3):304-311.
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. Ann
Rheum Dis. 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. Lancet.
2022;399(10341):2113-2128. doi: 10.1016/S0140-6736(22)00581-5.
- Crohn's disease. Symptoms and causes. Mayo Clinic. Accessed
March 8,
2023. https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304
- The facts about inflammatory bowel diseases. Crohn's &
Colitis Foundation of America. Accessed March 8, 2023.
https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf
- Pipeline. AbbVie. Accessed March 3, 2023.
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. 2022. Updated March 21, 2023. Accessed March
21, 2023. https://clinicaltrials.gov/ct2/show/NCT03725202
- A study to evaluate the efficacy and safety of upadacitinib in
participants with Takayasu arteritis (TAK) (SELECT-TAK).
ClinicalTrials.gov. Updated November 28, 2022. Accessed March 6,
2023. https://clinicaltrials.gov/ct2/show/NCT04161898
* Endoscopic response is defined as a decrease in simple
endoscopic score for Crohn's disease (SES-CD) of >50% from
baseline (or at least a 2-point reduction from baseline in patients
with a baseline score of 4) of the
induction.
† Clinical remission per SF/AP is defined as average
daily very soft or liquid stool frequency ≤2.8 AND abdominal pain
score ≤1.0 and neither greater than baseline.
‡ Corticosteroid-free clinical remission is defined as
discontinuation of corticosteroid and achievement of clinical
remission among subjects on corticosteroid at baseline in the
induction studies and is defined as without corticosteroid use for
90 days and achievement of clinical remission in the maintenance
study.
§ Mucosal healing is defined as SES-CD ulcerated surface
subscore of 0 in patients with SES-CD ulcerated surface subscore ≥
1 at baseline. Mucosal healing was a prespecified endpoint, not
controlled for multiplicity.
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