Filgotinib as monotherapy also hits primary endpoint in DARWIN 2 trial

  • 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

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Source:Galapagos NV