- RINVOQ (upadacitinib) is now approved by the European
Commission for the treatment of adult patients with moderately to
severely active ulcerative colitis who have had an inadequate
response, lost response or were intolerant to either conventional
therapy or a biologic agent1
- The approval is based on the results of three Phase 3
studies: two for induction and one for
maintenance1,2
- In these clinical trials, RINVOQ achieved the primary
endpoint of clinical remission (per Adapted Mayo Score) at week 8
in induction studies and week 52 in the maintenance study, and all
secondary endpoints, including clinical response and mucosal
healing1,2
- Safety results in ulcerative colitis were generally
consistent with the known safety profile of RINVOQ, with no new
important safety risks observed2,3-6
- Ulcerative colitis is a chronic, immune-mediated
inflammatory bowel disease (IBD) that can lead to substantial
burden and often disability among
patients.7-9 At least 6.8 million people
worldwide live with IBD, including ulcerative
colitis10
- The approval represents RINVOQ's fifth therapeutic
indication in the EU
NORTH
CHICAGO, Ill., July 26,
2022 /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]) for the treatment of adult patients with
moderately to severely active ulcerative colitis who have had an
inadequate response, lost response or were intolerant to either
conventional therapy or a biologic agent.*
"Our years of experience and long-term investment in IBD
research have given us invaluable insights into the challenges that
ulcerative colitis patients face, and a deep understanding of the
ongoing need for additional treatment options to help those still
suffering," said Thomas Hudson,
M.D., senior vice president, research and development, chief
scientific officer, AbbVie. "We celebrate today's approval of
RINVOQ by the EC as it meaningfully expands our ability to help
indicated patients in need of relief from ulcerative colitis."
The EC approval is supported by data from two induction studies,
U-ACHIEVE induction and U-ACCOMPLISH, and one maintenance study,
U-ACHIEVE maintenance.2 Statistical significance was
achieved for the primary endpoint and all secondary endpoints with
RINVOQ 45 mg in the two induction studies and both RINVOQ 15 mg and
30 mg in the maintenance study.
Clinical Remission†
- During the U-ACHIEVE and U-ACCOMPLISH induction trials, 26
percent and 33 percent of patients treated with RINVOQ 45 mg
achieved clinical remission at week 8, the primary endpoint,
compared to 5 percent and 4 percent of patients who received
placebo.2,11,12
- During the U-ACHIEVE maintenance trial, 42 percent and 52
percent of patients treated with RINVOQ 15 mg or 30 mg,
respectively, achieved clinical remission at week 52, the primary
endpoint, compared to 12 percent of patients who received
placebo.2,13
- Additionally, 57 percent and 68 percent of patients receiving
RINVOQ 15 mg or 30 mg, respectively, achieved corticosteroid-free
remission, defined as clinical remission (per Adapted Mayo Score)
and corticosteroid free for ≥90 days immediately preceding week 52
among patients who achieved clinical remission at the end of the
induction treatment, compared to 22 percent of patients on
placebo.2,13
Clinical Response & Mucosal Healing‡§
- Seventy-three and 74 percent of patients treated with RINVOQ 45
mg achieved clinical response (per Adapted Mayo Score) at week 8
compared to 27 and 25 percent of patients receiving placebo during
the U-ACHIEVE and U-ACCOMPLISH induction trials, respectively.
1,2,11,12,14
- In both trials, a significantly greater proportion of patients
experienced clinical response per partial Adapted Mayo Score
(symptomatic response) as early as week 2 (U-ACHIEVE: 60 percent vs
27 percent and U-ACCOMPLISH: 63 percent vs 26
percent).1,2,11,12,14
- Mucosal healing was observed in 36 percent and 44 percent of
patients treated with RINVOQ 45 mg in U-ACHIEVE and U- ACCOMPLISH,
respectively, at week 8, compared to 7 percent and 8 percent of
patients, respectively, who received placebo.1,2
- In the maintenance study at week 52, mucosal healing was
observed in 49 percent and 62 percent of patients treated with
RINVOQ 15 mg and 30 mg, respectively, compared to 14 percent who
received placebo.1,2,13
"Patients with ulcerative colitis live with unpredictable, often
painful symptoms that significantly impact their quality of life,
including emotional, social and economic impacts," said Séverine
Vermeire, M.D., Ph.D., professor of gastroenterology at University
Hospital Leuven in Leuven, Belgium. "RINVOQ demonstrated the ability to
help patients experience improvements in disease parameters such as
durable clinical remission and mucosal healing at week eight of
induction therapy and week 52 of maintenance therapy. These results
represent an exciting possibility for patients who continue to
experience active disease despite treatment with conventional or
biologic therapy."
In the placebo-controlled ulcerative colitis induction and
maintenance clinical trials, the overall safety findings were
generally consistent with the known safety profile of upadacitinib;
no new important safety risks were observed.1 The rates
of overall adverse events (AE), serious AEs, and AEs resulting in
treatment discontinuation were lower with upadacitinib compared to
placebo.1 The most commonly reported adverse reactions
(≥5 percent of patients) with RINVOQ 45 mg, 30 mg or 15 mg were
upper respiratory tract infection, blood CPK increased, acne,
neutropaenia, and rash.1 In the overall clinical
program, major cardiovascular events, thrombotic events, malignancy
excluding non-melanoma skin cancer, and gastrointestinal
perforation were reported infrequently (all <1.0 cases per 100
patient-years in patients who received at least one RINVOQ
dose).1
About the U-ACHIEVE Induction, U-ACCOMPLISH and U-ACHIEVE
Maintenance Studies2,6,15,16
The three Phase 3 studies are multicenter, randomized,
double-blind, placebo-controlled studies to evaluate the efficacy
and safety of RINVOQ 45 mg once daily as induction therapy, and
RINVOQ 15 mg and 30 mg once daily as maintenance therapy in
subjects with moderate to severe ulcerative colitis. The results of
these studies were published in The Lancet in May 2022. More information can be found on
http://www.clinicaltrials.gov (NCT03006068, NCT03653026,
NCT02819635).
About RINVOQ® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a
selective and reversible JAK inhibitor that is being studied in
several immune-mediated inflammatory
diseases.1,2,3-6,17,18 In human cellular assays, RINVOQ
preferentially inhibits signalling by JAK1 or JAK1/3 with
functional selectivity over cytokine receptors that signal via
pairs of JAK2.1
Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic
dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn's
disease, ulcerative colitis, giant cell arteritis and Takayasu
arteritis are ongoing.4-6,15-22
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.
Ankylosing spondylitis
RINVOQ is indicated for the treatment of active ankylosing
spondylitis (AS) 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 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. 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 compared to placebo. If alanine
transaminase (ALT) or aspartate transaminase (AST) increases are
observed and drug-induced liver injury is suspected, upadacitinib
should be interrupted until the 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 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 AS
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. 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.
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 serious 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
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 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.
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and maintenance therapy for moderately to severely active
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AbbVie News Center. Published March 16,
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* This approval 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.
† Clinical remission (per Adapted Mayo Score) is defined as
stool frequency subscore (SFS) ≤1 and not greater than baseline,
rectal bleeding subscore (RBS) of 0 and endoscopic subscore ≤1
without friability.
‡ Clinical response (per Adapted Mayo Score) is defined as a
decrease from baseline in the Adapted Mayo score ≥2 points and ≥30
percent from baseline, plus a decrease in RBS ≥1 or an absolute RBS
≤1.
§ Mucosal healing is defined as endoscopic subscore ≤1 without
friability.
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