NORTH CHICAGO, Ill.,
Oct. 29, 2020 /PRNewswire/
-- Late-breaking data analyses to be presented by AbbVie
(NYSE: ABBV) at the 29th European Academy of Dermatology
and Venereology (EADV) Virtual Congress show that significantly
more atopic dermatitis patients treated with upadacitinib (15
mg or 30 mg; once daily) monotherapy achieved improvement in
additional measures of skin clearance and reduction in itch
compared to placebo.1 These data are from the Phase 3
Measure Up 1 and Measure Up 2 studies, which support the recent
applications to the U.S. Food and Drug Administration and European
Medicines Agency, seeking approval for RINVOQ in adult and
adolescent patients with moderate to severe atopic dermatitis.
In both of the Measure Up 1 and 2 studies, significantly
more patients treated with either dose of upadacitinib achieved at
least a 90 percent improvement in the Eczema Area Severity Index
(EASI 90) compared to patients treated with placebo at week 16
(53/66 percent of patients receiving upadacitinib 15/30 mg versus 8
percent receiving placebo in Measure Up 1; 42/58 percent of
patients receiving upadacitinib 15/30 mg versus 5 percent receiving
placebo in Measure Up 2) [p<0.001]).1 Additionally,
for both doses of upadacitinib, the proportion of patients
achieving a clinically meaningful itch reduction was significantly
higher than placebo at week 4 and maintained through week
16.1 A clinically meaningful itch reduction was defined
as improvement in Worst Pruritus Numerical Rating Scale
(NRS)≥4.1
"I'm encouraged to see results showing a high proportion of
patients treated with upadacitinib achieved EASI 90, or almost
clear skin, and significant reduction in their itch," said lead
investigator Emma Guttman-Yassky,
M.D., Ph.D., professor of dermatology and immunology, director of
the center for excellence in eczema and laboratory for inflammatory
skin diseases and the incoming chair of the department of
dermatology at the Icahn School of Medicine at Mount Sinai in
New York.* "The speed and degree
of response with upadacitinib are meaningful to patients, many of
whom suffer from substantial burden of disease that can interfere
with daily life."
Earlier this year, AbbVie announced top-line data from Measure
Up 1 and Measure Up 2 showing upadacitinib (15 mg or 30 mg) met the
co-primary endpoints of EASI 75 and a validated Investigator's
Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1
(clear or almost clear) at week 16.1
At EADV, AbbVie will also present new analyses showing
significantly more patients reported improvements in quality of
life as measured by a Dermatology Life Quality Index (DLQI) score
of 0/1 after 16 weeks of treatment with either dose of
upadacitinib, compared to those on placebo.1 DLQI is a
measure of a patient's health-related quality of life, ranging from
0 to 30, with a score of 0 or 1 indicating the disease no longer
had an impact on their quality of life.5
These and additional data are being presented as part of the
"Late Breaking News" session (Abstract #D3T03.4B) on October 31 from 4:00-4:15
p.m. CET/10:00-10:15 a.m. CT,
during the EADV Virtual Congress.
Measure Up 1 and
Measure Up 2 Results**,1
|
|
Measure Up
1
|
Measure Up
2
|
|
Placebo
(n=281)
|
Upadacitinib 15
mg
(n=281)
|
Upadacitinib 30
mg
(n=285)
|
Placebo
(n=278)
|
Upadacitinib 15
mg
(n=276)
|
Upadacitinib 30
mg
(n=282)
|
EASI 75 at week
16a
|
16%
|
70%
|
80%
|
13%
|
60%
|
73%
|
vIGA-AD 0/1 at week
16b
|
8%
|
48%
|
62%
|
5%
|
39%
|
52%
|
EASI 90 at week
16c
|
8%
|
53%
|
66%
|
5%
|
42%
|
58%
|
Improvement in Worst
Pruritus NRS≥4 at week 4d
|
4%
|
51%
|
67%
|
4%
|
49%
|
61%
|
Improvement in Worst
Pruritus NRS≥4 at week 16d
|
12%
|
52%
|
60%
|
9%
|
42%
|
60%
|
DLQI 0/1 at week
16e
|
4%
|
30%
|
41%
|
5%
|
24%
|
38%
|
|
**Co-primary
endpoints were EASI 75 and vIGA-AD 0/1 at week 16. Co-primary
endpoints achieved p-values of <0.001. EASI 90 at week 16,
improvement in Worst Pruritus NRS≥4 at week 4 and DLQI 0/1 at week
16 were secondary endpoints. All secondary endpoints achieved
p-values of <0.001. Not all secondary endpoints are
shown.
|
a EASI 75 is defined as at least a 75
percent reduction in Eczema Area and Severity Index.
|
b vIGA-AD 0/1 is defined as a
validated Investigator Global Assessment for Atopic Dermatitis of
0/1 (clear or almost clear) with at least two grades of reduction
from baseline.
|
c EASI 90
is defined as at least a 90 percent reduction in Eczema Area and
Severity Index.
|
d Improvement in Worst Pruritus NRS≥4
is defined as an improvement (reduction) in Worst Pruritus NRS≥4.
The endpoint was analyzed for participants with pruritus NRS≥4 at
baseline.
|
e DLQI 0/1
was defined as a DLQI score of 0 or 1 among patients 16 years or
older with a DLQI≥1 at baseline.
|
No new safety risks were identified compared to those from
previous studies with RINVOQ.1-4 As previously reported,
during the 16-week placebo-controlled period in Measure Up 1,
serious adverse events (SAEs) were reported in 2.1 percent of
patients receiving upadacitinib 15 mg and 2.8 percent of patients
receiving either upadacitinib 30 mg or placebo.1 In
Measure Up 2, SAEs were reported in 1.8 percent of patients
receiving upadacitinib 15 mg, 2.5 percent of patients receiving
upadacitinib 30 mg and 2.9 percent of patients receiving
placebo.1 Serious infections were reported infrequently
in both Measure Up 1 and Measure Up 2.1 In Measure Up 1,
0.7 percent of patients receiving either upadacitinib 15 mg or 30
mg reported serious infections, and none were observed in patients
receiving placebo.1 In Measure Up 2, serious infections
were reported in 0.4 percent of patients receiving upadacitinib 15
mg and 0.7 percent of patients receiving either upadacitinib 30 mg
or placebo.1 No deaths, major adverse cardiac events
(MACE) or venous thromboembolic events (VTE) were reported in any
of the upadacitinib treatment groups in both
studies.1
Results from these studies are being submitted to journals for
publication.
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.6,7 It affects up to an
estimated 10 percent of adults and 25 percent of
adolescents.7,8 Between 20 and 46 percent of adults
with atopic dermatitis have moderate to severe
disease.9 The range of symptoms pose significant
physical, psychological and economic burden on individuals impacted
by the disease.7,10 Despite advancements in care,
patients continue to struggle with the signs and symptoms of the
disease.11
About the Measure Up 1 and Measure Up 2
Studies1
Measure Up 1 and Measure Up 2 are replicate Phase 3,
multicenter, randomized, double-blind, parallel-group,
placebo-controlled studies designed to evaluate the safety and
efficacy of upadacitinib monotherapy in adult and adolescent (12
years or older) patients with moderate to severe atopic dermatitis
who are candidates for systemic treatment. Patients were randomized
to upadacitinib 15 mg, upadacitinib 30 mg or placebo, followed by
either upadacitinib 15 mg or upadacitinib 30 mg at week 16.
The co-primary endpoints were the percentage of patients
achieving EASI 75 and a vIGA-AD score of 0/1 after 16 weeks of
treatment. Secondary endpoints included improvement in Worst
Pruritus NRS≥4 at week 4 and week 16, EASI 90 at week 16 and DLQI
0/1 at week 16. The trials are ongoing, and the long-term extension
period remains blinded to investigators and patients, to evaluate
the long-term safety, tolerability and efficacy of the two once
daily doses (15 mg and 30 mg) of upadacitinib in patients who have
completed the placebo-controlled period. More information on these
trials can be found at www.clinicaltrials.gov (NCT03569293 and
NCT03607422).
About RINVOQ™ (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is an
oral, once daily, selective and reversible JAK inhibitor studied in
several immune-mediated inflammatory diseases.1,12-19 It
was engineered to have greater inhibitory potency for JAK1 versus
JAK2, JAK3 and TYK2.2 In August
2019, RINVOQ received U.S. Food and Drug Administration
approval for adult patients with moderately to severely active
rheumatoid arthritis who have had an inadequate response or
intolerance to methotrexate. In December
2019, RINVOQ also received approval 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. The approved dose for RINVOQ in rheumatoid
arthritis is 15 mg. Phase 3 trials of RINVOQ in atopic dermatitis,
rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis,
Crohn's disease, ulcerative colitis, giant cell arteritis and
Takayasu arteritis are ongoing.1,13-19 Use of RINVOQ in
atopic dermatitis is not approved and its safety and efficacy have
not been evaluated by regulatory authorities.
Important Safety Information about RINVOQ™
(upadacitinib)20
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 ≥75 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. 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 are upper
respiratory tract infections (13.5%), nausea (3.5%), increased
blood creatine phosphokinase (2.5%), and cough (2.2%). The most
common serious adverse reactions were serious infections.
Please see the full SmPC for complete prescribing information
at www.EMA.europa.eu. Globally, prescribing information
varies; refer to the individual country product label for complete
information.
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 2019 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.
*Emma Guttman-Yassky, M.D.,
Ph.D., is a researcher/consultant for AbbVie.
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