NORTH CHICAGO, Ill., Aug. 24,
2021 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced the
European Commission (EC) approved RINVOQ®
(upadacitinib), an oral, selective and reversible JAK inhibitor,
for the treatment of moderate to severe atopic dermatitis in adults
and adolescents 12 years and older who are candidates for systemic
therapy.1 The recommended dose of RINVOQ for atopic
dermatitis in adults is 15 mg or 30 mg once daily based on
individual patient presentation, and 15 mg once daily for
adolescents (12-17 years of age) and adults 65 years and
older.1 RINVOQ can be used with or without topical
corticosteroids (TCS).1
"This is a significant milestone for AbbVie in our pursuit to
transform care in atopic dermatitis," said Michael Severino, M.D., vice chairman and
president, AbbVie. "We are excited to provide an additional
treatment option in Europe to help alleviate the burden of
unrelenting itch and rash that many of these patients struggle with
in daily life, despite available treatment options."
The EC approval is supported by data from one of the largest
registrational Phase 3 programs in atopic dermatitis with more than
2,500 adults and adolescents with moderate to severe
disease.1 These studies evaluated the efficacy and
safety of RINVOQ monotherapy (Measure Up 1 [MU1] and Measure Up 2
[MU2]) and with topical corticosteroids (AD Up [AU]) compared to
placebo.1 In all three studies, the co-primary endpoints
were at least a 75 percent improvement in the Eczema Area and
Severity Index (EASI 75) and validated Investigator's Global
Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 (clear or
almost clear) at week 16.1
"As a dermatologist researching and treating atopic dermatitis
for more than 25 years, I've seen first-hand the debilitating
impact this disease can have on a person's daily life," said
Alan Irvine, M.D., D.Sc., professor
of dermatology, Trinity College Dublin,
Ireland, and RINVOQ clinical study investigator. "Clinicians
need more tools to help them treat and manage this complex disease.
The degree and early onset of skin clearance and itch relief in the
RINVOQ Phase 3 clinical studies are very encouraging. The outcomes
have the potential to advance treatment goals for patients with
moderate to severe atopic dermatitis."
Highlights From the Global Phase 3 Atopic Dermatitis Clinical
Trial Program1
Across the Phase 3 studies, all primary and secondary
endpoints were met with 15 mg and 30 mg doses of RINVOQ
compared to placebo. Highlights include:
- Significantly more patients achieved EASI 75 at week 16 in the
RINVOQ 15 mg group (MU1: 70%; MU2: 60%; AU: 65%) and the RINVOQ 30
mg group (MU1: 80%; MU2: 73%; AU: 77%), compared to placebo (MU1:
16%; MU2: 13%; AU: 26%).
- Significantly more patients achieved vIGA-AD 0/1 at week 16 in
the RINVOQ 15 mg group (MU1: 48%; MU2: 39%; 40: 31%) and the RINVOQ
30 mg group (MU1: 62%; MU2: 52%; AU: 59%) compared to placebo (MU1:
8%; MU2: 5%; AU: 11%).
- Significantly more patients achieved clinically meaningful itch
reduction (improvement in Worst Pruritus NRS ≥4) in the RINVOQ 15
mg group (MU1: 52%; MU2: 42%; AU: 52%) and the RINVOQ 30 mg group
(MU1: 60%; MU2: 60%; AU: 64%) compared to placebo (MU1: 12%; MU2:
9%; AU: 15%) at week 16.
- Clinically meaningful itch reduction (improvement in Worst
Pruritus NRS ≥4) and skin clearance (EASI 75) were observed as
early as week 1 and week 2, respectively, in patients treated with
either dose of RINVOQ compared to those treated with placebo.
- Results at week 16 continued to be maintained through week 52
in patients treated with either dose of RINVOQ.
The most commonly reported adverse reactions (≥5% of patients)
with RINVOQ 15 mg or 30 mg were upper respiratory tract infection
(25.4%), acne (15.1%), herpes simplex (8.4%), headache (6.3%) and
increased blood creatine phosphokinase (CPK; 5.5%).1 The
most common serious adverse reactions were serious infections
(<1.0%).1
The Marketing Authorization means that RINVOQ is approved in all
member states of the European Union, as well as Iceland, Liechtenstein, Norway and Northern
Ireland. RINVOQ is already approved for the treatment of
moderate to severe atopic dermatitis in Russia, Saudi
Arabia, United Arab
Emirates, New Zealand and
Chile, and is currently under
review in the U.S. by the Food and Drug Administration (FDA).
*10,500 patients includes all patients across all arms (active
treatment and placebo) in 8 Phase 3 trials in rheumatoid arthritis,
2 in psoriatic arthritis, 1 in ankylosing spondylitis and 5 in
atopic dermatitis.2-9 This includes 344 adolescent
patients (aged 12 to 17 years) in the Phase 3 Measure Up 1, Measure
Up 2 and, AD Up studies in atopic dermatitis.1,2,5 Of
the total number of patients included in these trials, 6,280 were
randomized to receive RINVOQ at either dose.2-9
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.1,10-20 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 RINVOQ 15 mg is also approved by the U.S.
Food and Drug Administration (FDA) for adults with moderately to
severely active rheumatoid arthritis, and by the European
Commission for adults with moderate to severe active rheumatoid
arthritis, adults with active psoriatic arthritis (PsA) and adults
with active ankylosing spondylitis (AS). 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.12-20
Important EU Indications and Safety Information about
RINVOQ® (upadacitinib)1
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.
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.
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
increased, bronchitis, nausea, cough, aspartate transaminase
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.
Ankylosing spondylitis:
Overall, the safety profile observed in patients with active
ankylosing spondylitis treated with upadacitinib 15 mg was
consistent with the safety profile observed in patients with
RA.
Psoriatic arthritis:
Overall, the safety profile observed in patients with active
psoriatic arthritis treated with upadacitinib 15 mg was consistent
with the safety profile observed in patients with RA. A higher
incidence of acne and bronchitis was observed in patients treated
with upadacitinib 15 mg (1.3% and 3.9%, respectively) compared to
placebo (0.3% and 2.7%, respectively). A higher rate of serious
infections (2.6 events per 100 patient-years and 1.3 events per 100
patient-years, respectively) and hepatic transaminase elevations
(ALT elevations Grade 3 and higher rates 1.4% and 0.4%,
respectively) was observed in patients treated with upadacitinib in
combination with MTX therapy compared to patients treated with
monotherapy. There was a higher rate of serious infections in
patients ≥65 years of age, although data are limited.
Atopic dermatitis:
Dose-dependent changes in ALT increased and/or AST increased (≥ 3 x
ULN), lipid parameters, CPK values (> 5 x ULN), and neutropenia
(ANC < 1 x 109 cells/L) associated with
upadacitinib treatment were similar to what was observed in the
rheumatologic disease clinical studies. Based on limited data in
atopic dermatitis patients aged 65 years and older, there was a
higher rate of overall adverse reactions with the upadacitinib 30
mg dose compared to the 15 mg dose. 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.
This is not a complete summary of all safety
information.
Please see the RINVOQ full SmPC for complete prescribing
information at http://www.EMA.europa.eu.
Globally, prescribing information varies; refer to the
individual country product label for complete information.
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, 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 2020 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.
References:
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland
GmbH & Co. KG; August 2021. Available at:
https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
- Guttman-Yassky E., 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.
- Blauvelt A., et al. Efficacy and Safety of Upadacitinib vs
Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A
Randomized Clinical Trial. JAMA Dermatol. Published online
August 4, 2021.
doi:10.1001/jamadermatol.2021.3023.
- EPAR: RINVOQ [European Public Assessment Report]. AbbVie
Deutschland GmbH & Co. KG. June
2021. Available at:
https://www.ema.europa.eu/en/medicines/human/EPAR/rinvoq.
- Reich K, Teixeira HD, Bruin-Weller, et al. Safety and efficacy
of upadacitinib in combination with topical corticosteroids in
adolescents and adults with moderate-to-severe atopic dermatitis
(AD Up): results from a randomised, double-blind,
placebo-controlled, phase 3 trial. Lancet. 2021; 397(10290):
2169-2181.
- Zeng, X., et al. SAT0160 Efficacy and Safety of Upadacitinib In
Patients From China, Brazil, And
South Korea With Rheumatoid Arthritis Who Have Had Inadequate
Response To Conventional Synthetic Disease-Modifying Antirheumatic
Drugs. Ann Rheum Dis. 2020. 79:1020-1021.
- Rubbert-Roth A., et al. Trial of Upadacitinib or Abatacept in
Rheumatoid Arthritis. N Engl J Med. 2020;383(16):1511-1521.
doi:10.1056/NEJMoa2008250.
- Kameda H., et al. Efficacy and safety of upadacitinib in
Japanese patients with rheumatoid arthritis (SELECT-SUNRISE): a
placebo-controlled phase llb/lll study. Rheumatology (Oxford).
2020;59(11):3303-3313. doi:10.1093/rheumatology/keaa084.
- A Study to Evaluate Safety of Upadacitinib in Combination With
Topical Corticosteroids in Adolescent and Adult Participants With
Moderate to Severe Atopic Dermatitis (Rising Up).
ClinicalTrials.gov. 2020. Available at:
https://clinicaltrials.gov/ct2/show/NCT03661138. Accessed on
August 19, 2021.
- Cohen S., et al. Safety profile of upadacitinib in rheumatoid
arthritis: integrated analysis from the SELECT phase III clinical
programme. Ann Rheum Dis. 2020 Oct 28;80(3):304-11.
- Mease, P.J., et al. Upadacitinib in Patients with Psoriatic
Arthritis and Inadequate Response to Biologics: 56-Week Data from
the Randomized Controlled Phase 3 SELECT-PsA 2 Study. Rheumatol
Ther. 2021 Apr 28. doi: 10.1007/s40744-021-00305-z. Online ahead of
print.
- Pipeline – Our Science | AbbVie. AbbVie. 2021. Available
at: https://www.abbvie.com/our-science/pipeline.html. Accessed
on July 27, 2021.
- A Study to Evaluate Efficacy and Safety of Upadacitinib in
Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2).
ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed
on July 27, 2021.
- Evaluation of Upadacitinib in Adolescent and Adult Patients
With Moderate to Severe Atopic Dermatitis (Eczema) (Measure Up 1).
ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/ NCT03569293. Accessed
on July 27, 2021.
- 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: https://clinicaltrials.gov/ct2/show/NCT03345836. Accessed
on Accessed on July 27, 2021.
- 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: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed
on July 27, 2021.
- A Study Comparing Upadacitinib (ABT-494) to Placebo in Adults
With Rheumatoid Arthritis on a Stable Dose of Conventional
Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) Who Have
an Inadequate Response to csDMARDs Alone (SELECT-NEXT).
ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT02675426. Accessed
on July 27, 2021.
- A Study Comparing Upadacitinib (ABT-494) to Placebo and to
Adalimumab in Participants With Psoriatic Arthritis Who Have an
Inadequate Response to at Least One Non-Biologic Disease Modifying
Anti-Rheumatic Drug (SELECT - PsA 1). ClinicalTrials.gov. 2021.
Available at: https://clinicaltrials.gov/ct2/show/NCT03104400.
Accessed on July 27, 2021.
- A Study to Evaluate the Safety and Efficacy of Upadacitinib in
Participants With Giant Cell Arteritis (SELECT-GCA).
ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed
on July 27, 2021.
- A Study to Evaluate the Efficacy and Safety of Upadacitinib in
Subjects With Takayasu Arteritis (TAK) (SELECT-TAK).
ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT04161898. Accessed
on July 27, 2021.
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