- ACR20 scores up to 73% as once-daily
monotherapy at 12 weeks
- Statistically significant ACR20 and ACR50 responses at all
dose levels
- Onset of efficacy within first week of treatment in this
trial
- Safety profile in DARWIN 2 consistent with previous
filgotinib RA studies
Webcast presentation of the results to be held on
28 April 2015, 16.00 CET/10 AM EDT/ 8 AM PDT, +32 2 620 0138,
access code 6206795, more
call number info further down
MECHELEN, Belgium, April 27, 2015 (GLOBE
NEWSWIRE) -- Galapagos NV (Euronext:GLPG) announced today
that the selective JAK1 inhibitor filgotinib as once-daily
monotherapy showed rapid improvements in signs and symptoms of
moderately severe, active rheumatoid arthritis (RA) and met key
efficacy endpoints after 12 weeks of treatment in the DARWIN 2
Phase 2B study. The study achieved its primary endpoint at
all doses and demonstrated statistically significant improvements
in ACR20 response versus placebo after 12 weeks of treatment.
In addition, statistically significant ACR50 response and
DAS28(CRP) decrease were achieved with all dose levels.
Filgotinib was well tolerated in this study. Hemoglobin
levels increased. These first 12 week results in the ongoing
24 week study are consistent with the efficacy and safety profile
of filgotinib observed in prior clinical studies.
DARWIN 2 is an ongoing, 24 week, double-blind,
placebo-controlled evaluation of filgotinib, as once-daily
administration (QD dosing) at 3 dose levels. Results were reported
for 283 patients with moderate to severe rheumatoid arthritis who
showed an inadequate response to methotrexate. Filgotinib or
placebo was given as monotherapy. The patients were evaluated up to
12 weeks, the time of the primary endpoint of the study.
Galapagos expects to report the full 24 week results for DARWIN 2
in the 3rd quarter of this year.
Summary of the ACR responses and DAS28(CRP)
changes at 12 weeks of once-daily monotherapy:
|
Placebo n=72 |
50 mg n=72 |
100 mg n=70 |
200 mg n=69 |
ACR20 responders, NRI, % |
31 |
67*** |
66*** |
73*** |
ACR50 responders, NRI, % |
11 |
36** |
34** |
44*** |
ACR70 responders, NRI, % |
4 |
8 |
19* |
13 |
DAS28(CRP), LOCF, mean change from baseline |
-1.0 |
-1.7*** |
-2.0*** |
-2.3*** |
* p< 0.05 vs. placebo; ** p<0.01 vs.
placebo; *** p<0.001 vs. placebo ACR responses based on
intent to treat (ITT) analysis, with non-responder imputation
(NRI). Mean baseline DAS28(CRP) varied between 6.0 and 6.2. The
DAS28(CRP) is analyzed by ITT with last observation carried forward
(LOCF).
The results from this study show a rapid onset
of efficacy, with ACR20 response, investigator's assessment of
disease and patient-reported improvements (global assessment of
disease and pain) reaching statistical significance after one week
of treatment.
Over all dose groups including placebo, 1.8% of
patients stopped treatment during the study for safety reasons.
Within this low number of discontinuations, the distribution across
treatment groups is not disclosed to avoid individual treatment
unblinding while the study is ongoing. Serious (2% overall)
and non-serious treatment-emergent adverse events overall were
evenly spread over the dose groups including placebo. Infections
and infestations were the most common (15% for filgotinib vs 10%
for placebo), with only 2 (0.7%) serious infections which remain
blinded for the treatment group. Consistent with its
selective JAK1 inhibition, filgotinib treatment led to a
dose-dependent improvement in hemoglobin (up to 0.4 g/dL, or 3.4%
increase from baseline). A decline in neutrophils,
consistent with anti-inflammatory activity, was observed during the
first 4 weeks, with stable levels in the normal range
thereafter. No discontinuations due to anemia, neutropenia,
or increase in transaminases were reported. Dose-dependent,
well-balanced increases in LDL and HDL were observed.
"The results from the DARWIN 2 study are truly
exciting, with consistent efficacy meeting key endpoints across the
different geographical regions. If confirmed in longer-term
studies, selective inhibition of JAK1 by filgotinib may lead to a
differentiated safety profile without compromising efficacy," said
Professor Arthur Kavanaugh, MD, Professor of Medicine at the
University of California, San Diego (UCSD) School of Medicine, and
Principal Investigator for DARWIN 2.
"Once-daily monotherapy in DARWIN 2 led to
similar efficacy as that observed at the high doses in DARWIN 1,
where patients took once- or twice-daily filgotinib with
methotrexate. And we found the same fast onset of
action. These data support our belief that filgotinib could
be used prior to initiating anti-TNF therapy," said Dr Piet
Wigerinck, Chief Scientific Officer of Galapagos. "Selective
inhibition of JAK1 increases hemoglobin, which is important to
improve the patient's fatigue and thereby overall condition.
These 12-week monotherapy results in RA further support our belief
that filgotinib has a promising future to address a significant
medical need. We look forward to the final 24 week data for
both DARWIN 1 and 2, later this year."
About the DARWIN 2 trial and its measures
The primary endpoint of the DARWIN 2 study is efficacy in terms of
percentage of subjects achieving an ACR20 response after 12 weeks
of treatment. In accordance with the protocol for the DARWIN
2 study, at week 12, all subjects on placebo and those who received
50 mg once-daily filgotinib but did not achieve a 20% improvement
in swollen joint count and tender joint count have been
re-randomized to a 100 mg once-daily dose. Other subjects
will maintain their randomized treatment until week 24.
Secondary trial objectives include efficacy in terms of the
percentage of subjects achieving an ACR20 response at week 24,
ACR50 and ACR70 response and other disease activity measures, as
well as safety and tolerability and effects on fatigue and quality
of life.
The improvement of rheumatoid arthritis can be
assessed using composite scores as recommended by the American
College of Rheumatology, or ACR. The ACR criteria measure
improvement in tender and swollen joint counts and include other
parameters which take into account the patient's and physician's
assessment of disease, pain, and an anti-inflammatory biomarker.
These clinical and laboratory disease activity parameters are
combined to form a composite score and are expressed as percentages
of clinical response that are known as ACR20, ACR50, and ACR70. An
ACR20 score represents at least a 20% improvement in these criteria
and is considered a modest improvement in a patient's disease. An
ACR50 and ACR70 represent a minimal 50% and 70% improvement in the
response criteria, respectively, and each is considered evidence of
a substantial improvement in a patient's disease.
The DAS28(CRP), or the Disease Activity Score,
considers 28 tender and swollen joint counts, general health, plus
levels of an inflammatory biomarker, being CRP. DAS28(CRP) is
used to give an overall picture of the disease state, resulting in
a score on a scale from 0 to 10 indicating current RA disease
activity, whereby remission is less than or equal to 2.6, low
disease activity is less than or equal to 3.2, moderate
disease activity is less than or equal to 5.1, and high
disease activity is greater than 5.1.
Conference call and webcast presentation
Galapagos will conduct a conference call open to
the public tomorrow, 28 April 2015, at 16:00 CET/10 AM EDT/8 AM
PDT, which will also be webcast. To participate in the
conference call, please call one of the following numbers ten
minutes prior to commencement:
|
Confirmation Code: |
6206795 |
|
|
|
|
|
|
|
London, United Kingdom: |
+44 20 3478 5300 |
Toll free - United Kingdom: |
0800 279 4841 |
New York, NY, USA: |
+1 718 354 1357 |
Toll free - USA: |
1 877 280 1254 |
Amsterdam, Netherlands: |
+31 20 713 2790 |
Toll free - Netherlands: |
0800 020 2576 |
Brussels, Belgium: |
+32 2 620 0138 |
Toll free - Belgium: |
0800 58032 |
Paris, France: |
+33 1 76 77 22 29 |
Toll free - France: |
0805 631 580 |
A question and answer session will follow the
presentation of the results. Go to www.glpg.com to access the
live audio webcast. The archived webcast, PDF of the slides,
and a transcript will also be available on the Galapagos website
later in the day.
About Galapagos Galapagos
(Euronext:GLPG) (OTC:GLPYY) is a clinical-stage biotechnology
company specialized in the discovery and development of small
molecule medicines with novel modes of action, with a pipeline
comprising three Phase 2 programs, two Phase 1 trials, five
pre-clinical studies, and 25 discovery small-molecule and antibody
programs in cystic fibrosis, inflammation, and other
indications. In the field of inflammation, AbbVie and
Galapagos signed a collaboration agreement for the development and
commercialization of filgotinib. Filgotinib is an
orally-available, selective inhibitor of JAK1 for the treatment of
rheumatoid arthritis and potentially other inflammatory diseases,
currently in Phase 2B studies in RA and in Phase 2 in Crohn's
disease. Galapagos reported good activity and a favorable
safety profile at 12 weeks in both the DARWIN 1 and 2 trials in
RA. AbbVie and Galapagos also signed a collaboration
agreement in cystic fibrosis to develop and commercialize molecules
that address mutations in the CFTR gene. Potentiator GLPG1837
is currently in a Phase 1 trial, and corrector GLPG2222 is at the
pre-clinical candidate stage. GLPG1205, a first-in-class
inhibitor of GPR84 and fully-owned by Galapagos, is currently being
tested in a Phase 2 proof-of-concept trial in ulcerative colitis
patients. GLPG1690, a fully proprietary, first-in-class
inhibitor of autotaxin, has shown favorable safety in a Phase 1
trial and is expected to enter Phase 2 in idiopathic pulmonary
fibrosis. The Galapagos Group, including fee-for-service
subsidiary Fidelta, has approximately 400 employees, operating from
its Mechelen, Belgium headquarters and facilities in The
Netherlands, France, and Croatia. Further information at:
www.glpg.com
CONTACT
Galapagos NV Elizabeth Goodwin, Head of
Corporate Communications & IR Tel: +31 6 2291 6240
ir@glpg.com
Galapagos forward-looking statements This release may
contain forward-looking statements, including, without limitation,
statements concerning anticipated progress, objectives and
expectations regarding the commercial potential of our product
candidates, intended product development, clinical activity timing,
and other objectives and explanations, all of which involve certain
risks and uncertainties. These statements are often, but are not
always, made through the use of words or phrases such as
"believes," "anticipates," "expects," "intends," "plans," "seeks,"
"estimates," "may," "will," "could," "stands to," "continues," "we
believe," "we intend," as well as similar expressions. Such
forward-looking statements may involve known and unknown risks,
uncertainties and other factors which might cause the actual
results, financial condition, performance or achievements of
Galapagos, or industry results, to be materially different from any
historic or future results, financial conditions, performance or
achievements expressed or implied by such forward-looking
statements. Among the factors that may result in differences are
the inherent uncertainties associated with competitive
developments, clinical trial and product development activities,
regulatory approval requirements and estimating the commercial
potential of our product candidates. Given these uncertainties, the
reader is advised not to place any undue reliance on such
forward-looking statements. These forward-looking statements
speak only as of the date of publication of this document.
Galapagos expressly disclaims any obligation to update any such
forward-looking statements in this document to reflect any change
in its expectations with regard thereto or any change in events,
conditions or circumstances on which any such statement is based,
unless required by law or regulation.
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