NORTH CHICAGO, Ill.,
Feb. 17, 2018 /PRNewswire/
-- AbbVie (NYSE: ABBV), a global research and
development-based biopharmaceutical company, today presented new
positive results from a Phase 2b
dose-ranging study evaluating upadacitinib, an investigational,
once-daily oral JAK1-selective inhibitor, in adult patients with
moderate to severe atopic dermatitis. These results were featured
during the "Late-Breaking Research: Clinical Trials" session at the
2018 American Academy of Dermatology (AAD) Annual Meeting in
San Diego. Upadacitinib is not
approved by regulatory authorities and its safety and efficacy have
not been established.
In September of 2017, AbbVie announced positive top-line results
from this Phase 2b study, including
an evaluation of the primary endpoint – mean percent change in
Eczema Area and Severity Index (EASI) at week 16 versus
placebo.1 The press release is available here.
In today's presentation, across all doses (30/15/7.5 mg
once-daily), additional exploratory results showed significant
reduction of select symptoms of atopic dermatitis in upadacitinib
patients, including reduction in itch (pruritus) at week 1 and
improvement in the extent and severity of skin lesions at week
2.1
"Patients living with atopic dermatitis are seeking relief from
the intense itching and skin lesions - which can have a profound
impact," said Emma Guttman-Yassky,
M.D., Ph.D., Professor of Dermatology and Immunology, Icahn School
of Medicine at Mount Sinai Medical Center and lead study
investigator. "For this patient population, given the severity of
their disease and available targeted therapies, additional options
are needed."
Evaluation of Signs and Severity (Eczema Area and
Severity Index)
- In an exploratory analysis, results at week 2 of treatment with
upadacitinib showed all dose groups (30/15/7.5 mg once-daily)
achieved significant improvement in extent and severity of atopic
dermatitis, as measured by the mean percent change in Eczema Area
and Severity Index (EASI) score.1
Mean Percentage
Change from Baseline in EASI Score***
|
Dose
|
Week
2
|
Week 16 (Primary
Endpoint)
|
30 mg
(n=42)
|
59%*
|
74%*
|
15 mg
(n=42)
|
56%*
|
62%*
|
7.5 mg
(n=42)
|
39%*
|
39%**
|
Placebo
(n=39)
|
9% (n=37)
|
23%
|
*P<0.001,
**P<0.05
|
***Eczema Area and
Severity Index (EASI) score is a tool used to measure the extent
(area) and severity of atopic eczema.
|
Evaluation of Reduction in Itch (Pruritus)
- In an exploratory analysis, results at week 1 showed reduction
in itch in patients treated with upadacitinib, as measured by the
pruritus numerical rating scale (NRS).1
Mean Percent
Change from Baseline in Pruritus (Itch) Numerical Rating
Scale*****
|
Dose
|
Week
1
|
Week
2
|
Week
16
|
30 mg
(n=42)
|
36%*
|
58%*
|
69%*
|
15 mg
(n=37)
|
28%*
|
46%*
|
48%*
|
7.5 mg
(n=40)
|
19%*(n=39)
|
29%*
(n=39)
|
40%****
|
Placebo
(n=37)
|
-1%
|
-2%
|
10%
|
*P<0.001,
****P<0.01
|
*****Itch will be
rated from 0 (no itch) to 10 (worst imaginable itch).
|
The most common adverse events were upper respiratory tract
infection, atopic dermatitis worsening and acne.1
Serious adverse events across treatment groups occurred in 0/1/2
patients in the 30/15/7.5 mg groups compared to 1 patient on
placebo.1 No herpes zoster, malignancies, deaths or
cases of pulmonary embolism (PE) or deep vein thrombosis (DVT)
occurred in the first 16 weeks of this Phase 2b study.1
"This study showed that upadacitinib significantly reduced itch
and improved skin lesions supporting its potential to be a
meaningful treatment option for patients," said Marek Honczarenko, M.D., Ph.D., vice president,
immunology development, AbbVie. "We strive to make a remarkable
impact on patients' lives and we look forward to advancing this
development program into registration-enabling studies this
year."
About Atopic Dermatitis
Atopic dermatitis, a chronic
inflammatory skin disease, is characterized by skin erosion, oozing
and crusting, redness, intense itching and dry skin.10
Symptoms can appear as a rash on the skin, or the skin may become
thickened and leathery.11
About the Phase 2b Upadacitinib
Study1
This dose-ranging study is an ongoing
88-week Phase 2b, randomized,
double-blind, parallel-group, placebo-controlled multicenter study
designed to evaluate the safety and efficacy of upadacitinib in
adult patients with moderate to severe atopic dermatitis not
adequately controlled by topical treatments, or for whom topical
treatments were not medically advisable. In Period 1, subjects were
randomized in a 1:1:1:1 ratio to one of four treatment groups
(three dosing groups, 30/15/7.5 mg once-daily, and one placebo
group) for 16 weeks. The primary endpoint of the study was mean
percentage change from baseline in Eczema Area and Severity Index
(EASI) score at 16 weeks in comparison with placebo. Secondary
endpoints included proportion of patients achieving EASI 90, EASI
75, an Investigator Global Assessment (IGA) of 0 or 1 and percent
change in pruritus/itch numerical rating scale from day 1
(baseline) to week 16 in comparison with placebo. More information
on this trial can be found at www.clinicaltrials.gov
(NCT02925117).
About Upadacitinib
Discovered and developed by
AbbVie, upadacitinib is an investigational oral agent engineered to
selectively inhibit JAK1, which plays an important role in the
pathophysiology of immune-mediated disorders.2,3 Phase 3
trials of upadacitinib in rheumatoid arthritis, psoriatic arthritis
and Crohn's disease are ongoing.4-6 Upadacitinib is also
being evaluated as a potential treatment for ankylosing
spondylitis.7 AbbVie plans to begin
registration-enabling studies in atopic dermatitis, ulcerative
colitis and giant cell arteritis this year.8,9
In January 2018, the U.S. Food and
Drug Administration granted Breakthrough Therapy Designation for
upadacitinib in adult patients with moderate to severe atopic
dermatitis who are candidates for systemic therapy. Breakthrough
Therapy Designation is intended to expedite the development and
review of medicines with preliminary clinical evidence that
indicate that the investigational treatment may demonstrate
substantial improvement over existing therapies on one or more
clinically significant endpoints.12
Upadacitinib is an investigational oral agent and is not
approved by regulatory authorities. Safety and efficacy have not
been established.
About AbbVie
AbbVie is a global, research and
development-based biopharmaceutical company committed to developing
innovative advanced therapies for some of the world's most complex
and critical conditions. The company's mission is to use its
expertise, dedicated people and unique approach to innovation to
markedly improve treatments across four primary therapeutic areas:
immunology, oncology, virology and neuroscience. In more than
75 countries, AbbVie employees are working every day to advance
health solutions for people around the world. For more information
about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on
Twitter, Facebook or 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, 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 2017 Annual Report on Form
10-K, which has been filed with the Securities and Exchange
Commission. 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.
_______________________
1 Guttman-Yasky, E et al. Primary Results from a Phase
2b, Randomized, Placebo-Controlled
Trial of Upadacitinib for Patients with Atopic Dermatitis. American
Academy of Dermatology. February
2018.
2 Voss, J, et al; Pharmacodynamics Of a Novel Jak1
Selective Inhibitor In Rat Arthritis and Anemia Models and In
Healthy Human Subjects. [abstract]. Arthritis Rheum 2013;65 Suppl
10 :2374. DOI: 10.1002/art.2013.65.issue-s10
3 Pipeline – Our Science | AbbVie. AbbVie. 2017.
Available at: https://www.abbvie.com/our-science/pipeline.html.
Accessed on January 29, 2018.
4 A Study Comparing ABT494 to Placebo in Subjects With
Rheumatoid Arthritis on a Stable Dose of Conventional Synthetic
DiseaseModifying Antirheumatic Drugs (csDMARDs) Who Have an
Inadequate Response to csDMARDs Alone (SELECT-NEXT).
ClinicalTrials.gov. 2018. Available at:
https://clinicaltrials.gov/ct2/show/NCT02675426. Accessed on
January 29, 2018.
5 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.
2018. Available at:
https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on
January 29, 2018.
6 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. 2018. Available at:
https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on
January 29, 2018.
7 A Study Evaluating the Safety and Efficacy of
Upadacitinib in Subjects With Active Ankylosing Spondylitis (SELECT
Axis 1). ClinicalTrials.gov. 2018. Available
at: https://clinicaltrials.gov/ct2/show/study/NCT03178487.
Accessed on January 29, 2018.
8 A Study to Evaluate the Safety and Efficacy of ABT-494
for Induction and Maintenance Therapy in Subjects With Moderately
to Severely Active Ulcerative Colitis. ClinicalTrials.gov. 2018.
Available at:
https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed
on January 29, 2018.
9 Phase 2b AD Dose Ranging
Study (40wk) N=160. ClinicalTrials.gov. 2018. Available
at: https://clinicaltrials.gov/ct2/show/NCT02925117. Accessed
on January 29, 2018.
10 Hebert AA. Review of pimecrolimus cream 1% for
the treatment of mild to moderate atopic dermatitis. Clin Ther. 2006;28(12): 1972-82.
11 Williams HC. Clinical practice. Atopic dermatitis. N
Engl J Med. 2005;352(22):2314-24. 12 U.S. Food and Drug
Administration.
12 Fact Sheet: Breakthrough Therapies.
https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm.
Accessed on January 29, 2018.
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SOURCE AbbVie