- ACR20 scores up to 80% at 12 weeks
- Statistically significant ACR50 and DAS28(CRP) scores
with all doses
- Patient-reported improvements observed after one week
of treatment
- Safety profile is consistent with previous filgotinib
RA studies
Webcast presentation of the results to be held on
15 April 2015, 16.00 CET/10 AM EDT/7 AM PDT, +32 2 789
2126, access code 5188327
, more call number info further down
Galapagos NV (Euronext: GLPG) announced today that the
selective JAK1 inhibitor filgotinib showed improvements in signs
and symptoms of active rheumatoid arthritis and met key efficacy
endpoints after 12 weeks of treatment with filgotinib as an add-on
to methotrexate, or MTX, in the DARWIN 1 Phase 2B
study. The study achieved its primary endpoint with a statistically
significant improvement in ACR20 score versus placebo after 12
weeks of treatment at a daily dose of 200 mg. Statistically
significant ACR50 scores were achieved with all dose levels and
dose regimens. Statistically significant improvement in DAS28(CRP)
was seen within one week. In this study, filgotinib was well
tolerated. Hemoglobin levels increased. The total
cholesterol over HDL ratio improved with
dose. These first results in the ongoing 24 week study are
consistent with the efficacy/safety profile of filgotinib observed
in the prior 4-week clinical studies.
DARWIN 1 is an ongoing, 24 week, double-blind,
placebo-controlled evaluation of filgotinib, as once- and
twice-daily administration (QD and BID dosing) at 3 daily dose
levels. Results were reported for 594 patients with moderate to
severe rheumatoid arthritis who showed an inadequate response to
methotrexate and who remained on their background therapy of
methotrexate. These patients received filgotinib or placebo
and 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 1 around the middle of the year.
Summary of the ACR/DAS28(CRP) scores at 12 weeks
treatment:
|
|
Once-daily dosing |
Twice-daily dosing |
|
Placebo n=86 |
50 mg n=82 |
100 mg n=85 |
200 mg n=86 |
25 mg n=86 |
50 mg n=85 |
100 mg n=84 |
ACR20 responders, NRI, % |
45 |
56 |
62 |
69* |
57 |
59 |
80*** |
ACR50 responders, NRI, % |
15 |
32* |
39** |
43*** |
28* |
34* |
55*** |
ACR70 responders, NRI, % |
8 |
16 |
20 |
24* |
14 |
19 |
31** |
DAS28(CRP), mean change from baseline, LOCF § |
-1.2 |
-1.8* |
-2.2*** |
-2.5*** |
-1.9** |
-2.1*** |
-2.8*** |
* p< 0.05 vs. placebo; ** p<0.01 vs.
placebo; *** p<0.001 vs. placebo; ACR scores 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 on a last observation carried
forward (LOCF) basis.
Overall, there were no statistically relevant
differences for the once-daily and twice-daily dosing regimens.
The results suggest a rapid onset of activity, already after
one week of treatment.
Over all dose groups including placebo, 1.7% of
patients stopped treatment during the study for safety reasons.
Because of the low number of discontinuations, the actual
distribution across treatment groups is not disclosed to prevent
individual treatment unblinding while the study is still ongoing.
Serious (1.3% overall) and non-serious treatment-emergent
adverse events were evenly spread over the dose groups including
placebo. The rare frequency adverse events remain blinded for
the treatment group and include 3 cases (0.5% of patients) of
serious infections. Consistent with its selective JAK1
inhibition, filgotinib treatment led to a dose-dependent
improvement in hemoglobin (up to 0.4 g/dL, or 3.7% increase from
baseline). All lipid fractions including HDL and LDL
increased, with the largest percentage increase in HDL leading to
an improved total cholesterol over HDL ratio (atherogenic index) at
200 mg/day.
"The last decade saw an important progress in RA
treatment with biologicals," said Prof. René Westhovens from the
University of Leuven, Belgium, and Principal Investigator for
DARWIN 1. "The current data with this oral drug spell hope
for a potential future treatment option that combines fast onset of
action and ease of administration. I am particularly
impressed by the rapid improvement reported by the patients.
Also the increase in hemoglobin is important for my patients,
as this may lessen fatigue and enhance their overall
well-being."
"I am very pleased to see that filgotinib
treatment in DARWIN 1, one of the largest Phase 2 studies in RA to
date, shows consistent efficacy with fast onset of action. Its
selective inhibition of JAK1 also leads to a differentiated safety
profile, as measured by an improvement in hemoglobin and overall
lipid profile. Today's results with 12 weeks' treatment with
filgotinib met the key efficacy endpoints and are in line with what
Galapagos showed in two previous 4-week studies in RA
patients. Based on these 12-week results in RA, we believe
that filgotinib has a promising future to address a significant
medical need. We look forward to seeing the DARWIN 2
monotherapy results in just a few weeks," said Dr Piet Wigerinck,
Chief Scientific Officer of Galapagos.
About the DARWIN 1 trial and its
measures The primary endpoint of the DARWIN 1 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 1 study, at week 12, subjects on placebo or
lower doses of filgotinib who have not achieved 20% improvement in
swollen joint count and tender joint count will be re-randomized
automatically to another treatment arm with either a 50 mg (twice
daily) or 100mg (once daily) dose. Subjects in the other
groups 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. 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 >5.1.
Conference call and webcast presentation
Galapagos will conduct a conference call open to
the public tomorrow, 15 April 2015, at 16:00 CET/10 AM EDT/7 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: |
5188327 |
|
|
|
|
London, United Kingdom: |
+44 20 3427 1903 |
|
Toll free - United Kingdom: |
0800 279 4977 |
|
New York, United States of America: |
+1646 254 3366 |
|
Toll free - United States of America: |
1877 280 1254 |
|
Amsterdam, Netherlands: |
+31 20 716 8256 |
|
Toll free - Netherlands: |
0800 020 2577 |
|
Brussels, Belgium: |
+32 2 789 2126 |
|
Toll free - Belgium: |
0800 58032 |
|
Paris, France: |
+33 1 76 77 22 24 |
|
Toll free - France: |
0805 631 579 |
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 20 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. 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
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believe," "we intend," as well as similar expressions. Such
forward-looking statements may involve known and unknown risks,
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results, financial condition, performance or achievements of
Galapagos, or industry results, to be materially different from any
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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
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unless required by law or regulation.
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