NORTH CHICAGO, Ill.,
April 25, 2018 /PRNewswire/ -- AbbVie
(NYSE: ABBV), a research-based global biopharmaceutical company,
today announced positive results from the ongoing Phase
2b/3 SELECT-SUNRISE clinical trial,
showing that at 12 weeks, all doses of upadacitinib (7.5 mg, 15 mg
and 30 mg, once-daily) met the study's primary endpoint of
ACR20a versus placebo.1 Certain key efficacy
endpoints were also achieved versus placebo.1 The study,
conducted in Japan, evaluates
upadacitinib, an investigational oral JAK1-selective inhibitor, in
adult Japanese patients with moderate to severe rheumatoid
arthritis who are on a stable dose of conventional synthetic
disease-modifying antirheumatic drugs (csDMARDs) and have had an
inadequate response to csDMARDs.1 These data will be
presented during an oral presentation at the Japan College of Rheumatology (JCR) 2018
Annual Scientific Meeting in Tokyo
on Saturday, April 28, 2018.
Upadacitinib is not approved by regulatory authorities and its
safety and efficacy have not been established.
SELECT-SUNRISE is a local dose-ranging study in Japanese
patients and is part of AbbVie's robust global upadacitinib SELECT
clinical trial program, which is evaluating more than 4,000
patients with moderate to severe rheumatoid arthritis.
"We are encouraged by these data, which show that upadacitinib
provides improvements in important measures such as achieving ACR
response and clinical remission, in people living with rheumatoid
arthritis in Japan," said
Michael Severino, M.D., executive
vice president, research and development and chief scientific
officer, AbbVie. "SELECT-SUNRISE reflects our continued commitment
to offering innovative solutions with the potential to improve the
lives of Japanese patients living with this serious, debilitating
condition."
Rheumatoid arthritis, which affects an estimated 1 million
people in Japan, is a chronic and
debilitating disease.16, 17 Despite increasing
availability of a range of treatments in Japan, some patients with rheumatoid arthritis
still do not achieve clinical remission or tight control of their
disease.16
Results at week 12 showed that of patients receiving an oral
once-daily dose of upadacitinib 7.5/15/30 mg, 76/84/80 percent achieved ACR20,
respectively, compared to 43 percent of patients receiving placebo
(p<0.001).1 As early as week one, significantly
more patients on upadacitinib achieved ACR20 compared to placebo
(31/25/34 percent in the 7.5/15/30 mg
upadacitinib groups, respectively, compared to 8 percent in the
placebo group, p<0.01/0.05/0.01).1 Additionally,
significantly more patients receiving upadacitinib also achieved
ACR50a and ACR70a responses compared to
placebo.1 Among upadacitinib patients receiving the
7.5/15/30 mg doses, ACR50 was
achieved by 41/65/58 percent, respectively, compared to 16 percent
with placebo (p<0.01/0.001/0.001), and ACR70 was achieved by
20/35/28 percent, respectively, compared to 2 percent with placebo
(p<0.01/0.001/0.001).1
The study also showed that a significantly higher proportion of
upadacitinib patients across all doses achieved low disease
activityc and clinical remissionb at week 12
compared to patients receiving placebo.1 Low
disease activity was achieved by 53/69/72 percent of upadacitinib
patients in the 7.5/15/30 mg groups,
respectively, compared to 18 percent in the placebo group
(p<0.001).1 Clinical remission was achieved by
37/57/50 percent of upadacitinib patients in the 7.5/15/30 mg groups, respectively, compared to 6
percent in the placebo group (p<0.001).1 Patients
receiving upadacitinib also had greater improvements in physical
function, as measured by the Health Assessment
Questionnaire-Disability Index (HAQ-DI), and decreased severity of
morning stiffness.1
SELECT-SUNRISE
Efficacy Results at Week 12†
|
|
Placebo
(n=49)
|
Upadacitinib
7.5 mg
(n=49)
|
Upadacitinib
15 mg
(n=49)
|
Upadacitinib
30 mg
(n=50)
|
ACR20a
|
43%
|
76%
|
84%
|
80%
|
ACR50a
|
16%
|
41%
|
65%
|
58%
|
ACR70a
|
2%
|
20%
|
35%
|
28%
|
Clinical Remission
(DAS28-CRP)b
|
6%
|
37%
|
57%
|
50%
|
Low Disease
Activity (DAS28-CRP)c
|
18%
|
53%
|
69%
|
72%
|
†All week 12 endpoints shown in the
table achieved p-values of <0.001 except ACR50/70 responses with
7.5 mg upadacitinib which achieved p-values of <0.01. Not all
secondary endpoints shown.
|
a
ACR20/50/70 is defined as American College of Rheumatology 20
percent/50 percent/70 percent improvements in both tender and
swollen joint counts, plus 3 of the following: patient assessments
of pain, global disease activity and physical function, physician
global assessment of disease activity and acute phase
reactant.
|
b Clinical
remission was based on Disease Activity Score with 28 joint counts
(C-reactive protein) (DAS28 [CRP]) less than less than
2.6.
|
c Low
disease activity was defined by a clinical response Disease
Activity Score with 28 joint counts (C-reactive protein) (DAS28
[CRP]) less than or equal to 3.2.
|
The safety profile of upadacitinib during the 12-week reporting
period was consistent with previously reported
results.1-7 No new safety signals were
detected.1 Serious adverse events occurred in
2/2/10 percent of the 7.5/15/30 mg upadacitinib groups, respectively,
compared to 0 percent in the placebo group.1 Serious
infection occurred in 0/2/6 percent of the upadacitinib
7.5/15/30 mg groups, compared to 0
percent in the placebo group.1 There were no major
adverse cardiovascular events reported in the trial.1
There were no deaths, no events of pulmonary embolism (PE) or deep
vein thrombosis (DVT) reported.1 Across the SELECT
rheumatoid arthritis program, including both the placebo-controlled
and extension periods, the rate of DVT and PE remains consistent
with the background rate for the RA patient population.1-5,
18-20
About SELECT-SUNRISE1
SELECT-SUNRISE is an ongoing Phase 2b/3 study designed to evaluate the safety and
efficacy of upadacitinib compared to placebo in adult Japanese
patients with moderate to severe rheumatoid arthritis who are on a
stable dose of csDMARDs and have an inadequate response to
csDMARDs. In addition, the study is also intended to confirm dose
response in the efficacy of upadacitinib 7.5 mg, 15 mg and 30 mg in
the Japanese population. The study includes two periods. The first
period of the study is a 12 week randomized, placebo-controlled,
double-blind period designed to compare the safety and efficacy of
a once-daily dose of upadacitinib (7.5 mg, 15 mg or 30 mg) versus
placebo. Period 2 is a blinded long-term extension period to
evaluate the long-term safety, tolerability and efficacy of
upadacitinib 30 mg, 15 mg, 7.5 mg in subjects who have completed
Period 1. At week 12, patients on placebo, were equally switched
(pre-assigned at baseline) to receive a once-daily dose of
upadacitinib 7.5 mg, 15 mg or 30 mg. The primary endpoint of the
study is the proportion of patients achieving an ACR20 response at
week 12. Other key efficacy endpoints include the proportion of
patients achieving ACR50, ACR70, clinical remission and low disease
activity at week 12 as well as the change from baseline to week 12
in Health Assessment Questionnaire-Disability Index (HAQ-DI) and
severity of morning stiffness. More information on this trial can
be found at www.clinicaltrials.gov (NCT02720523).
About the SELECT Study Program
The robust SELECT Phase 3 rheumatoid arthritis program evaluates
more than 4,000 patients with moderate to severe rheumatoid
arthritis in six studies. The studies include assessments of
efficacy, safety and tolerability across multiple rheumatoid
arthritis patient populations. Key measures of efficacy evaluated
include ACR responses, Disease Activity Score (DAS28-CRP) and
inhibition of radiographic progression. More information on these
trials can be found at www.clinicaltrials.gov (NCT02706847,
NCT03086343, NCT02629159, NCT02706873, NCT02706951, NCT02675426).
SELECT-SUNRISE is a Phase 2b/3
clinical trial program that is evaluating 197 patients with
moderate to severe rheumatoid arthritis in Japan. More information on SELECT-SUNRISE
trial can be found at www.clinicaltrials.gov (NCT02720523).
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.8,9 Phase 3 trials of
upadacitinib in rheumatoid arthritis, psoriatic arthritis and
Crohn's disease are ongoing and it is also being investigated to
treat ulcerative colitis, ankylosing spondylitis, atopic dermatitis
and giant cell arteritis.10-15,21
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 AbbVie. Data on File, ABVRRTI66173.
2 AbbVie. Data on File, ABVRRTI66053.
3 AbbVie. Data on File, ABVRRTI65458.
4 AbbVie. Data on File, ABVRRTI64730.
5 AbbVie. Data on File, ABVRRTI64466.
6 Kremer JM, et al. A Phase 2b study of ABT-494, a selective JAK1 inhibitor,
in patients with rheumatoid arthritis and an inadequate response to
anti-TNF therapy. Arthritis Rheumatol 2016;
(doi:10.1002/art.39801): July 7 [Epub
ahead of print].
7 Genovese MC, et al. A randomized Phase 2b study of ABT-494, a selective JAK1 inhibitor
in patients with rheumatoid arthritis and an inadequate response to
methotrexate. Arthritis Rheumatol 2016;(doi: 10.1002/art.39808):
July 7 [Epub ahead of print].
8 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
9 Pipeline – Our Science | AbbVie. AbbVie. 2017.
Available at:
https://www.abbvie.com/our-science/pipeline.html. Accessed on
April 18, 2018.
10 A Study Comparing ABT494 to Placebo in Subjects 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. 2018. Available at:
https://clinicaltrials.gov/ct2/show/NCT02675426. Accessed on
April 18, 2018.
11 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
April 18, 2018.
12 A Study of the Efficacy and Safety of Upadacitinib
(ABT-494) in Subjects With Moderately to Severely Active Crohn's
Disease Who Have Inadequately Responded to or Are Intolerant to
Biologic Therapy. Clinicaltrialsgov. 2018. Available at:
https://www.clinicaltrials.gov/ct2/show/NCT03345836. Accessed on
April 18, 2018.
13 A Study Evaluating the Safety and Efficacy of
Upadacitinib in Subjects With Active Ankylosing Spondylitis (SELECT
Axis 1). 2018. Available
at: https://clinicaltrials.gov/ct2/show/study/NCT03178487.
Accessed on April 18, 2018.
14 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 April 18, 2018.
15 A Study to Evaluate ABT-494 in Adult Subjects With
Moderate to Severe Atopic Dermatitis. ClinicalTrials.gov. 2018.
Available at: https://clinicaltrials.gov/ct2/show/NCT02925117.
Accessed on April 18, 2018.
16 Yamanaka H, et al. Estimates of the prevalence of and
current treatment practices for rheumatoid arthritis in
Japan using reimbursement data
from health insurance societies and the IORRA cohort (I). Mod
Rheumatol 2013. DOI 10.1007/s10165-013-0863-6. Available at
https://link.springer.com/article/10.1007/s10165-013-0863-6.
Accessed on April 18, 2018.
17 McInnes I, Schett G. The Pathogenesis of Rheumatoid
Arthritis. New England Journal of Medicine. 2011;365(23):2205-2219.
doi:10.1056/nejmra1004965.
18 Kim SC, et al. Risk of Venous Thromboembolism in
Patients with Rheumatoid Arthritis. Arthritis Care & Research.
Vol. 65, No. 10, October 2013, pp
1600–1607.
19 AbbVie. Data on File, ABVRRTI64959.
20 AbbVie. Data on File, ABVRRTI66056.
21 AbbVie's (ABBV) CEO Richard
Gonzalez on Q4 2017 Results - Earnings Call Transcript.
Available at:
https://seekingalpha.com/article/4140615-abbvies-abbv-ceo-richard-gonzalez-q4-2017-results-earnings-call-transcript.
Accessed on April 18, 2018.
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