NORTH CHICAGO, Ill.,
June 25, 2021 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced the European Medicines Agency's (EMA)
Committee for Medicinal Products for Human Use (CHMP) adopted a
positive opinion recommending the approval of RINVOQ®
(upadacitinib), an oral, selective and reversible JAK inhibitor,
for the expanded use in adults (15 mg or 30 mg, once daily) and
adolescents 12 years and older (15 mg, once daily) with moderate to
severe atopic dermatitis who are candidates for systemic
therapy. RINVOQ is being studied in several immune-mediated
inflammatory diseases.4-10
The CHMP positive opinion was supported by data from the global
Phase 3 program evaluating more than 2,500 patients with moderate
to severe atopic dermatitis across three global pivotal studies:
Measure Up 1, Measure Up 2 and AD Up.1,2 Across the
three studies, both doses of RINVOQ met all primary and secondary
endpoints, demonstrating rapid and significant improvement in skin
clearance and reduction in itch compared to placebo at week 16 and
other time points (p<0.001) in patients with moderate to severe
atopic dermatitis.1,2 The most commonly reported adverse
events in patients treated with RINVOQ were acne, nasopharyngitis
and upper respiratory tract infections.1,2
"This milestone is an important step forward in our journey to
improve care for people living with atopic dermatitis," said
Michael Severino, M.D., vice
chairman and president, AbbVie. "Despite available treatments, many
people with moderate to severe forms of this disease continue to
experience a relentless and burdensome cycle of skin and itch
symptoms. We are encouraged that the CHMP has recognized RINVOQ's
potential as an additional treatment option for these
patients."
The CHMP positive opinion is a scientific recommendation for
marketing authorization to the European Commission, which
authorizes marketing approval in the European Union. The Marketing
Authorization will be valid in all member states of the European
Union, as well as Iceland,
Liechtenstein, Norway and Northern
Ireland. If approved, this will be the fourth indication for
RINVOQ, and RINVOQ will be the first JAK inhibitor in the European
Union to treat moderate to severe atopic dermatitis
in both adults and adolescents 12 years and older.3
About Atopic Dermatitis
Atopic dermatitis is a chronic, relapsing inflammatory condition
characterized by a cycle of intense itching and scratching leading
to cracked, scaly, oozing skin.11,12 It affects up to an
estimated 10 percent of adults and 25 percent of
children.12,13 Between 20 and 46 percent of adults with
atopic dermatitis have moderate to severe disease.14 The
range of symptoms poses significant physical, psychological and
economic burden on individuals impacted by the
disease.12,15
About the RINVOQ Atopic Dermatitis Global Phase 3 Study
Program
The global Phase 3 program evaluated more than 2,500 patients
worldwide across three global pivotal studies: Measure Up 1,
Measure Up 2 and AD Up.1,2 The studies evaluated the
efficacy and safety of RINVOQ (15 mg and 30 mg, once daily), with
and without topical corticosteroids (TCS), in adults and
adolescents with moderate to severe atopic dermatitis who were
candidates for systemic therapy.1,2 The co-primary
endpoints across all three studies were at least a 75 percent
improvement in Eczema Area and Severity Index (EASI 75) and a
validated Investigator's Global Assessment for Atopic Dermatitis
(vIGA-AD) score 0/1 at week 16.1,2 Secondary endpoints
included reduction of itch defined as
≥4 point improvement in Worst Pruritus Numerical Rating
Scale (NRS) from baseline at week 16 and other
timepoints, as well as EASI 90 and EASI
100 at week 16.1,2 More information on this
program can be found at www.clinicaltrials.gov (NCT03569293,
NCT03607422, NCT03568318).
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 In human cellular assays, RINVOQ
preferentially inhibits signaling by JAK1 or JAK1/3 with functional
selectivity over cytokine receptors that signal via pairs of
JAK2.3 In August
2019, RINVOQ received U.S. FDA approval for adult patients
with moderately to severely active rheumatoid arthritis who have
had an inadequate response or intolerance to methotrexate. RINVOQ
is approved by the European Commission for the treatment of adult
patients 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 (DMARDs); 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; and for the treatment of active ankylosing spondylitis
(AS) in adult patients who have responded inadequately to
conventional therapy. The approved dose for RINVOQ in these
indications is 15 mg. Phase 3 trials of RINVOQ in axial
spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell
arteritis and Takayasu arteritis are
ongoing.4-10 Use of RINVOQ in atopic dermatitis is
not approved and its safety and efficacy are under evaluation by
regulatory authorities.
Important EU Safety Information about RINVOQ®
(upadacitinib)3
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.
Use in combination with other potent immunosuppressants is not
recommended.
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/oesophageal
candidiasis, and cryptococcosis have been reported with
upadacitinib. Prior to initiating upadacitinib, consider the risks
and benefits of treatment in patients with chronic or recurrent
infection or with a history of a serious or opportunistic
infection, in patients who have been exposed to TB or have resided
or travelled in areas of endemic TB or endemic mycoses, and in
patients with underlying conditions that may predispose them to
infection. Upadacitinib therapy should be interrupted if a patient
develops a serious or opportunistic infection. As there is a higher
incidence of infections in patients ≥65 years of age, caution
should be used when treating this population.
Patients should be screened for TB before starting upadacitinib
therapy. Anti-TB therapy should be considered prior to initiation
of upadacitinib in patients with previously untreated latent TB or
in patients with risk factors for TB infection.
Viral reactivation, including cases of herpes zoster, were
reported in clinical studies. The risk of herpes zoster appears to
be higher in Japanese patients treated with upadacitinib. Consider
interruption of therapy if a patient develops herpes zoster until
the episode resolves. Screening for viral hepatitis and monitoring
for reactivation should be performed before starting and during
therapy with upadacitinib.
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.
The risk of malignancies, including lymphoma is increased in
patients with rheumatoid arthritis (RA). Immunomodulatory medicinal
products may increase the risk of malignancies, including lymphoma.
The clinical data are currently limited and long-term studies are
ongoing. Malignancies, including non-melanoma 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.
Absolute neutrophil count <1000 cells/mm3,
absolute lymphocyte count <500 cells/mm3, or
haemoglobin levels <8 g/dL were reported in <1% of
patients in clinical trials. Treatment should not be initiated, or
should be temporarily interrupted, in patients with these
haematological abnormalities observed during routine patient
management.
RA patients have an increased risk for cardiovascular disorders.
Patients treated with upadacitinib should have risk factors (e.g.,
hypertension, hyperlipidaemia) managed as part of usual standard of
care.
Upadacitinib treatment was associated with increases in lipid
parameters, including total cholesterol, low-density lipoprotein
cholesterol, and high-density lipoprotein cholesterol. The effect
of these lipid parameter elevations on cardiovascular morbidity and
mortality has not been determined.
Treatment with upadacitinib was associated with an increased
incidence of liver enzyme elevation compared to placebo. If
increases in ALT or AST are observed during routine patient
management and drug-induced liver injury is suspected, upadacitinib
therapy should be interrupted until this diagnosis is excluded.
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. Risk factors that should be considered in
determining the patient's risk for DVT/PE include older age,
obesity, a medical history of DVT/PE, patients undergoing major
surgery, and prolonged immobilisation. If clinical features of
DVT/PE occur, upadacitinib treatment should be discontinued and
patients should be evaluated promptly, followed by appropriate
treatment.
The most commonly reported adverse drug reactions were upper
respiratory tract infections, bronchitis, nausea, blood creatine
phosphokinase (CPK) increased and cough. The most common serious
adverse reactions were serious infections.
Overall, the safety profile observed in patients with active
psoriatic arthritis treated with upadacitinib 15 mg was consistent
with rheumatoid arthritis. A higher incidence of acne and
bronchitis was observed in patients treated with upadacitinib
compared to placebo. A higher rate of serious infections and
hepatic transaminase elevations was observed in patients treated
with upadacitinib in combination with MTX compared to
monotherapy.
Please see the 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, 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 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:
- 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, randomized
controlled phase 3 studies. Lancet.
doi:10.1016/s0140-6736(21)00588-2.
- Reich K., 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
randomized, double-blind, placebo-controlled phase 3 trial. Lancet.
doi:10.1016/s0140-6736(21)00589-4.
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland
GmbH & Co. KG; May 2021.
Available at:
https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
- Pipeline – Our Science | AbbVie. AbbVie. 2021. Available
at: https://www.abbvie.com/our-science/pipeline.html. Accessed
on June 1, 2021.
- A Study to Compare Safety and Efficacy of Upadacitinib to
Dupilumab in Adult Participants With Moderate to Severe Atopic
Dermatitis (Heads Up). ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT03738397. Accessed
on June 1, 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 June 1, 2021.
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled
Study of ABT-494 for the Induction of Symptomatic and Endoscopic
Remission in Subjects With Moderately to Severely Active Crohn's
Disease Who Have Inadequately Responded to or Are Intolerant to
Immunomodulators or Anti-TNF Therapy. ClinicalTrials.gov. 2021.
Available at: https://clinicaltrials.gov/ct2/show/NCT02365649.
Accessed on Accessed on June 1, 2021.
- A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in
Participants With Moderately to Severely Active Ulcerative Colitis
(U-ACCOMPLISH). ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT03653026. Accessed
on June 1, 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 June 1, 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 June 1, 2021.
- Nutten S. Atopic Dermatitis: Global Epidemiology and Risk
Factors. Ann Nutr Metab 2015;66(suppl 1):8–16. doi:
10.1159/000370220.
- Weidinger, S., et al. Atopic dermatitis. Nat Rev Dis Primers 4,
1(2018). doi: 10.1038/s41572-018-0001-z.
- Eichenfield L.F., et al. Guidelines of care for the management
of atopic dermatitis: section 1. Diagnosis and assessment of atopic
dermatitis. J Am Acad Dermatol. 2014;70(2):338-351.
doi:10.1016/j.jaad.2013.10.010.
- Shrestha S., et al. Burden of Atopic Dermatitis in the United States: Analysis of Healthcare
Claims Data in the Commercial, Medicare, and Medi-Cal Databases.
Adv Ther. 2017;34(8):1989–2006.
- EFA. Atopic Eczema: Itching for Life Report. 2018. Available
at:
https://www.efanet.org/images/2018/EN_-_Itching_for_life_Quality_of_Life_and_costs_for_people_with_severe_atopic_eczema_in_Europe_.pdf.
Accessed on June 1, 2021.
View original
content:http://www.prnewswire.com/news-releases/chmp-recommends-approval-of-rinvoq-upadacitinib-for-the-treatment-of-atopic-dermatitis-301319936.html
SOURCE AbbVie