Galapagos BE0003818359

Galapagos 2017. De inhoudelijke discussie

1. NielsjeB 25 september 2017 14:42

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   Helemaal gemist, de abstracts van de ACR 2017.
   
   2017 ACR/ARHP Annual Meeting, November 3 - 8 in San Diego, California acrabstracts.org/search/
   
   Late breaking abstracts komen nog (submission deadline 26 september).
   Bekijk voor alle tabellen/figuren e.d. de abstract via de links.
2. NielsjeB 25 september 2017 14:43

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   ABSTRACT NUMBER: 1189
   Favorable Human Safety, Pharmacokinetics and Pharmacodynamics of the Adamts-5 Inhibitor GLPG1972, a Potential New Treatment in Osteoarthritis
   Ellen van der Aar1, Sonia Dupont2, Liesbeth Fagard1, Marina De Smet1, David Amantini2, Staffan Larsson3, André Struglics3, L. Stefan Lohmander4, Frédéric Vanhoutte1 and Julie Desrivot2, 1Galapagos NV, Mechelen, Belgium, 2Galapagos SASU, Romainville, France, 3Clinical Sciences, Lund University, Lund, Sweden, 4Orthopaedics, Clinical Sciences Lund, Lund University, Lund, Sweden
   
   Background/Purpose:
   
   Increased aggrecanase activity is a well-known trigger factor for osteoarthritis (OA), initiating loss of cartilage aggrecan that precedes more severe cartilage degradation. A disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) is a key aggrecanase in humans and is a relevant target for the development of disease-modifying OA drugs (DMOADs).
   GLPG1972 is a potent small molecule inhibitor of ADAMTS-5 displaying high selectivity versus a number of other zinc metalloproteases. The anti-catabolic activity of GLPG1972 was shown in murine and human cartilage explants, and its DMOAD activity was demonstrated in the destabilization of the medial meniscus (DMM) mouse model.
   In the current study, the safety, tolerability, pharmacokinetics and pharmacodynamics of GLPG1972 in healthy male subjects were evaluated.
   
   Methods:
   
   GLPG1972 was administered as single oral doses (60 mg up to 2100 mg) or multiple doses (300 mg/day to 1050 mg/day for 14 days) formulated as a solution. Ascending single doses were evaluated in an alternating fashion between two panels of 8 male healthy subjects and multiple doses were evaluated sequentially in 3 groups of 8 male healthy subjects. In both parts, 6 subjects received GLPG1972 and 2 placebo. Plasma and urine were collected at several time points and intervals for the quantification of GLPG1972 by LC-MS/MS. Pharmacodynamics was assessed by measurement of the aggrecan ARGS neoepitope levels in plasma by an enzyme-linked immunosorbent assay.
   
   Results:
   
   Administration of single (up to 2100 mg) and multiple (up to 1050 mg q.d.) ascending oral doses of GLPG1972 in healthy subjects was well tolerated, with no clinically relevant effects on ECGs, vital signs or laboratory parameters.
   
   GLPG1972 given as a single oral dose in fasted state was rapidly absorbed with a median tmax range of 1 to 4 h and eliminated with a terminal half-life of approximately 10 h. The rate of absorption decreased with higher doses, whereas the plasma exposure in terms of AUC increased dose-proportionally. After once-daily dosing for 14 days in fed state, GLPG1972 plasma exposure (both Cmax and AUC) increased dose-proportionally over the entire dose range. Pharmacokinetic steady state was reached after 2 dosing days, with minimal accumulation. The excretion of unchanged GLPG1972 in urine over a 24 h period was low (<11% of the administered dose).
   
   The aggrecan ARGS neoepitope levels decreased progressively over time during treatment with GLPG1972 but not with placebo. The extent of the pharmacodynamic effect was similar for the 3 tested doses. The maximal reduction in plasma concentrations of aggrecan ARGS neoepitope was about 60% at day 14 versus baseline. No plateau had been attained on day 14, suggesting that it may take longer to obtain the maximum effect.
   
   Conclusion:
   
   GLPG1972 was shown to be safe and well-tolerated in healthy male subjects with a suitable pharmacokinetic profile and a marked decrease of the aggrecan ARGS neoepitope biomarker, indicating target engagement. These data and the preclinical data package confirm the potential of GLPG1972 to be a potential DMOAD treatment. GLPG1972 will be progressed to a Phase 2 study in osteoarthritis.
   
   acrabstracts.org/abstract/favorable-h...
3. NielsjeB 25 september 2017 14:43

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   • NielsjeB

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   ABSTRACT NUMBER: 497
   The JAK1 Selective Inhibitor Filgotinib Regulates Both Enthesis and Colon Inflammation in a Mouse Model of Psoriatic Arthritis
   Catherine Robin-Jagerschmidt1, Stéphanie Lavazais1, Florence Marsais1, Maté Ongenaert2, Alain Monjardet1, Angélina Cauvin1, Corinne Saccomani1, Isabelle Parent1, Didier Merciris1, Emilie Chanudet1, Roland Blanqué1, Monica Borgonovi1, Liên Lepescheux1, Marielle Auberval1, Sonia Dupont1, Philippe Clément-Lacroix1 and René Galien1, 1Galapagos SASU, Romainville, France, 2Galapagos NV, Mechelen, Belgium
   
   Background/Purpose:
   
   Because of their pleotropic role in cytokine signaling, Janus Kinases (JAKs) are key players in inflammatory diseases. Among the 4 members of the JAK family (JAK1, JAK2, JAK3, TYK2), JAK1 has been demonstrated as a validated target in inflammatory diseases with filgotinib (GLPG0634, GS-6034) displaying efficacy and safety in several phase 2 studies in rheumatoid arthritis (RA) patients. Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease characterized by the association of skeletal involvement and extra-skeletal symptoms such as psoriasis and Inflammatory Bowel Disease (IBD) with common findings including enthesitis and dactylitis. Current treatments include anti-TNFa, anti-IL-17 and anti-IL-12/IL-23 antibodies with varying success rates. The involvement of several pro-inflammatory cytokines suggests that therapies targeting JAKs may be effective. To gain insight in the potential of a JAK1-selective inhibitor in PsA, we evaluated filgotinib efficacy in a mouse model of PsA induced by the overexpression of IL-23.
   
   Methods:
   
   Overexpression of IL-23 was induced by hydrodynamic delivery of mIl23 enhanced Episomal Expression Vector (SBI) to male B10.RIII mice1. Evolution of paw and finger inflammation was assessed by clinical scoring as well as by in vivo molecular imaging (Bruker In-Vivo Xtreme imaging system). Enthesis, colon and fingers were collected for transcriptomic analysis. Using immunohistochemistry, infiltration of immune inflammatory cells and pSTAT3 positive cells, were analyzed in Achilles’ enthesis, subcutaneous area and skin. Colon was also collected for histology and gene expression analysis.
   
   Results:
   
   High levels of IL-23 were maintained during the time-course of the study and were correlated with severity of finger and paw swelling and asscociated with inflammation of enthesis and finger as observed in PsA patients. Only moderate inflammation of the colon was observed. Filgotinib significantly improved clinical scoring and tended to prevent neutrophil/granulocyte infiltration in paw (notably at earlier time points) while strongly decreasing immune cell infiltration in the skin. Transcriptomic analysis of enthesis, fingers and colon showed that filgotinib reversed the effect of IL-23 for a consistent number of genes. Notably, expression of some upregulated inflammatory genes in enthesis and/or fingers (CCL20, CXCL1, IL-22, MMP9 and TNFa) as well as the target-related gene Mx2 were reduced. Filgotinib also significantly counteracted pSTAT3 induction in the subcutaneous area and in the epidermis (mainly concentrated in proliferating keratinocytes) further demonstrating target engagement in the diseased tissue.
   
   Conclusion:
   
   In a mouse model of PsA, filgotinib improved global clinical score and decreased signs of inflammation in hindlimbs. Target engagement both in hindlimbs and colon was also demonstrated. These data support the evaluation of filgotinib in patients with PsA.
   
   References:
   
   1- Sherlock et al. 2012 Nature Med 7:1069–1076
   
   acrabstracts.org/abstract/the-jak1-se...
   
   ABSTRACT NUMBER: 504
   Monotherapy with Filgotinib, a JAK1-Selective Inhibitor, Reduces Disease-Related Biomarkers in Rheumatoid Arthritis Patients
   Peter C. Taylor1, René Galien2, Annegret Van der Aa3, Corinne Jamoul3, Pille Harrison3, Chantal Tasset3, Yang Pan4, Lovely Goyal4, Wanying Li4 and Jacqueline Tarrant4, 1Kennedy Institute of Rheumatology, London, United Kingdom, 2Galapagos SASU, Romainville, France, 3Galapagos NV, Mechelen, Belgium, 4Gilead Sciences, Foster City, CA
   
   Background/Purpose: The JAK1 selective inhibitor filgotinib (GLPG0634, GS-6034) has been evaluated in a 24-week phase 2B study (DARWIN 2) as monotherapy in active rheumatoid arthritis (RA) patients who were methotrexate inadequate responders and has shown a good safety and efficacy profile1. A broad range of serum biomarkers were measured to characterize the mode of action of filgotinib.
   
   Methods: Serum samples from RA patients who received either placebo (PBO), or filgotinib monotherapy at 100mg or 200mg once daily (QD) were collected at baseline, weeks 4 and 12 and analyzed for 35 biomarkers by validated single- or multi-plex immunoassays. Median % changes from baseline for biomarkers are reported. Wilcoxon rank-sum test assessed the significance of the difference between filgotinib treated groups and PBO.
   
   Results: Filgotinib monotherapy was associated with significant reductions in a broad panel of immune- and tissue-related biomarkers relevant to RA, compared to placebo (27/35 markers). The largest reductions were in the pro-inflammatory markers IL-6, SAA, and CRP (58-68% median reduction from baseline to week 12, p<0.01). Other top-ranked biomarkers by effect size were related to joint degradation (MMP1, 3, YKL-40), immune cell recruitment (CXCL10, CXCL13), and TH17/reg cells (IL-23 and IL-10) (reductions of 28-31%, p<0.05 for all). These effects were present from week 4 and were maintained at week 12. Other biomarker changes also support down-modulation of TH1 (IL-2, IFN-?, IL-12), TH2 (IL-4, IL-5, IL-13), B cell (CXCL13, IL-7, IL-21), and myeloid cells (GM-CSF, MIP-1a). Filgotinib monotherapy did not increase leptin above PBO-levels.
   
   Conclusion: Filgotinib reduces the systemic levels of pro-inflammatory and RA-associated tissue-derived biomarkers. These effects on biomarkers in multiple disease processes and immune cell subsets provide insight into the efficacy shown by filgotinib evaluated as monotherapy in the Phase 2B study1.
   
   References: 1Kavanaugh A, et al. Ann Rheum Dis 2017; 76: 1009–1019.
   
   acrabstracts.org/abstract/monotherapy...
   
4. NielsjeB 25 september 2017 14:44

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   • NielsjeB

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   ABSTRACT NUMBER: 510
   Association between Clinical Response and Normalization of Patient-Reported Outcome Measures in Rheumatoid Arthritis: Post-Hoc Analysis from Two Phase 2b Filgotinib Studies
   Mark C. Genovese1, Annegret Van der Aa2, Corinne Jamoul2, Chantal Tasset2, Pille Harrison2, René Westhovens3 and Arthur Kavanaugh4, 1Stanford University Medical Center, Palo Alto, CA, 2Galapagos NV, Mechelen, Belgium, 3University Hospitals Leuven on behalf of the CareRA Study Group, Leuven, Belgium, 4Medicine, University of California, San Diego, La Jolla, CA
   
   Background/Purpose:
   
   Filgotinib (GLPG0634, GS-6034) is an oral, selective JAK1 inhibitor that has demonstrated safety and efficacy data in two 24-week placebo-controlled phase 2B studies as add-on to methotrexate and as monotherapy in active rheumatoid arthritis (RA) patients with inadequate response to MTX (MTX-IR)1,2.
   
   The objective is to evaluate the association between normalization of patient-reported outcome measures (PRO) and clinical response (ACR20) in MTX-IR RA patients treated with either filgotinib or placebo, as add-on to methotrexate (DARWIN 1), or as monotherapy (DARWIN 2).
   
   Methods:
   
   Patients with active RA were randomized in a double-blind manner to placebo (PBO) or one of 3 daily doses of filgotinib (FIL, 50mg, 100mg or 200mg) as once daily (DARWIN 1 and DARWIN 2) or twice daily regimen (DARWIN 1) for 24 weeks .This post-hoc analysis at week 12 (W12) included patients treated FIL 100mg and 200mg QD (selected Phase 3 doses), and PBO. PRO included SF-36 (mental and physical components: MCS and PCS respectively; cut-off 50), FACIT-F (cut-off 40), and HAQ-DI (cut-off 0.5).
   
   Results:
   
   594 and 283 patients with active RA were randomized in DARWIN 1 and 2 respectively. In DARWIN 1, 44%, 64%, and 69% of patients on PBO, FIL 100mg QD and FIL 200mg QD respectively achieved ACR20 response at W12; in DARWIN 2 the respective response was 29%, 66%, and 72%. For all PRO parameters (SF-36 MCS, SF-36 PCS, FACIT-F and HAQ-DI) and in both studies, a higher proportion of patients with normalized scores was achieved in ACR20 responders compared to non-responders at W12 across treatment groups (Table 1). .
   
   Conclusion:
   
   This post-hoc analysis of two phase 2B studies in MTX-IR RA patients after 12 weeks of treatment suggests that normalization of PRO is associated with the ACR20 response, regardless of treatment with filgotinib and background MTX.
   
   References
   
   1Westhovens R, et al. Ann Rheum Dis 2017;76:998-1008; 2Kavanaugh A, et al.Ann Rheum Dis 2017;76:1009-1019.
   
   acrabstracts.org/abstract/association...
   
   ABSTRACT NUMBER: 519
   Filgotinib, a Selective Janus Kinase 1 Inhibitor, Has No Effect on QT Interval in Healthy Subjects
   Kacey Anderson1, Hao Zheng2, Chohee Yun3, Ellen Kwan4, Ann Qin1, Florence Namour5, Brian P. Kearney1 and Yan Xin1, 1Clinical Pharmacology, Gilead Sciences, Inc., Foster City, CA, 2Gilead Sciences, Inc., Foster City, CA, 3Clinical Research, Gilead Sciences, Inc, Foster City, CA, 4Clinical Operations, Gilead Sciences, Inc, Foster City, CA, 5Galapagos NV, Romainville, France
   
   Background/Purpose:
   
   Filgotinib is a potent and selective Janus kinase 1 (JAK1) inhibitor being developed to treat inflammatory diseases. Safety pharmacology studies and Phase 1 studies indicate that there is a low risk of QT prolongation by filgotinib treatment. This dedicated Phase 1 study was conducted to evaluate the potential effect of filgotinib on the QT interval prolongation in healthy subjects per the International Conference on Harmonization (ICH) E14 guidance.
   
   Methods:
   
   52 healthy adults were randomized to receive a single dose of moxifloxacin 400 mg (positive control) or once daily doses of filgotinib 200 mg (top therapeutic dose), filgotinib 450 mg (supratherapeutic dose), or placebo for 7 days. There was a washout period of 9 days between each dosing period. Digital ECGs were collected in triplicates within 5 minutes at matched time points on the 1st day (predose) and 7th day (postdose) with 24 hours measurements for each treatment on the 7th day. QTc (QTcF and QTcI) were derived and average of triplicates provided time-matched QTc. Subjects with large QTc or QTc change from baseline were summarized. Changes from baseline in time-matched QTc were fit to a mixed effect model, and difference of QTc change between filgotinib treatments or moxifloxacin vs placebo were quantified. PK of filgotinib was evaluated, and safety was monitored throughout study. The 90% confidence intervals (CIs) were constructed for the ratios of geometric least squares means of filgotinib PK parameters (AUCtau, Cmax, and Ctau) for 450 mg vs. 200 mg daily dose. The association between QTc and plasma concentrations of filgotinib was explored.
   
   Results:
   
   46 (88.5%) subjects completed study drug treatments. The mean (range) age of subjects was 38 (20-55) years, 39 (75%) subjects were female, 28 (53.8%) were white and 15 (28.8%) were hispanic or latino.
   
   Lack of QTcF prolongation has been demonstrated at both doses of filgotinib. The upper limits of the 2-sided 90% CI for mean difference in QTcF between 200 mg or 450 mg vs placebo were less than 10 msec (= 8.35 msec) at all time points. Similar results were observed with QTcI. Assay sensitivity was demonstrated using moxifloxacin at 400 mg, with the lower 96.7% CI for mean difference in QTcF above 5 msec (= 8.32 msec) at 2, 3, and 4 hours post dose. Filgotinib 450 mg provided 2.1-fold higher Cmax than 200 mg. There were no clinically relevant relationships between change from baseline (placebo-corrected) in QTcF/QTcI and plasma concentrations of filgotinib.
   
   Overall, 8 (15.7%), 15 (30.0%), 0 (0.0%), and 5 (10.0%) subjects experienced treatment-related AEs during filgotinib 200 mg, filgotinib 450 mg, placebo, and moxifloxacin treatment periods, respectively. No serious or severe (= Grade 3) AEs occurred, and the majority of the AEs reported were Grade 1 (mild) in severity. No Grade 4 laboratory abnormalities occurred. There were no clinically significant trends in vital signs, or safety ECG recordings.
   
   Conclusion:
   
   Filgotinib does not affect QTc interval by definition of a negative thorough QT study per ICH E14 guidance at 200 mg (top therapeutic dose) and 450 mg (supratherapeutic dose; 2.1-fold higher Cmax than 200 mg).
   
   acrabstracts.org/abstract/filgotinib-...
   
5. NielsjeB 25 september 2017 14:44

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   • NielsjeB

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   ABSTRACT NUMBER: 534
   Effect of Baseline MTX Dose on Clinical Efficacy and Safety in Rheumatoid Arthritis Patients Treated with Filgotinib: Post-Hoc Analysis from a Phase 2B Study
   René Westhovens1, Annegret Van der Aa2, Corinne Jamoul2, Chantal Tasset2 and Pille Harrison2, 1KU Leuven Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, Leuven, Belgium, 2Galapagos NV, Mechelen, Belgium
   
   Background/Purpose:
   
   Filgotinib (GLPG0634, GS-6034) is an oral, selective JAK1 inhibitor that has demonstrated safety and efficacy data in two 24-week placebo-controlled phase 2B studies as add-on to methotrexate and as monotherapy in active rheumatoid arthritis (RA) patients with inadequate response to MTX (MTX-IR)1,2.The objective was to assess the effect of MTX dose on clinical efficacy and safety in MTX-IR RA patients treated with filgotinib as add-on to background MTX for 24 weeks.
   
   Methods:
   
   Patients with active RA on stable dose of MTX were randomized in a double-blinded manner to receive either placebo (PBO) or one of 3 daily doses of filgotinib (50mg, 100mg or 200mg) as once or twice daily regimen for 24 weeks1. This post-hoc analysis includes patients treated with the selected Phase 3 filgotinib doses, 100mg and 200mg QD, and PBO for the efficacy parameters, and all dose groups for the safety analysis. MTX dose was categorized as low (=12.5mg/wk), medium (>12.5 to <17.5 mg/wk) or high (=17.5mg/wk).
   
   Results:
   
   Baseline disease activity was high and similar across the three MTX subgroups, with an overall mean DAS28(CRP) score of 6.10, mean HAQ-DI of 1.73, mean CDAI score of 42.10 and mean SDAI score of 44.57. Across all MTX subgroups, patients on filgotinib 100mg or 200mg QD for 24 weeks showed efficacy over PBO, as measured by change from baseline in DAS28(CRP), CDAI, SDAI, HAQ-DI, and ACR20 response. No pattern was observed to suggest that the baseline MTX dose had any effect on filgotinib efficacy. The incidences of TEAE and serious TEAE were comparable regardless of the MTX dose (Table 2).
   
   Conclusion:
   
   Post-hoc analysis of a phase 2B study in MTX-IR RA patients suggests that filgotinib treatment at 100mg and 200mg QD on the background of MTX is consistently associated with improved clinical outcomes compared to placebo, across all key efficacy parameters, irrespective of MTX dose. The safety profile was overall favorable and consistent with previous studies in RA with filgotinib, regardless of MTX dose.
   
   References
   
   1Westhovens R, et al. Ann Rheum Dis 2017;76:998-1008; 2Kavanaugh A, et al.Ann Rheum Dis 2017;76:1009-1019.
   
   acrabstracts.org/abstract/effect-of-b...
   
   ABSTRACT NUMBER: 537
   No Effect of Baseline Serum CRP Levels on Clinical Efficacy Parameters in Rheumatoid Arthritis Patients Treated with Filgotinib: Post Hoc Analysis from Two Phase 2B Studies
   Arthur Kavanaugh1, Annegret Van der Aa2, Corinne Jamoul2, Chantal Tasset2, Pille Harrison2 and René Westhovens3, 1Medicine, University of California, San Diego, La Jolla, CA, 2Galapagos NV, Mechelen, Belgium, 3Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium
   
   Background/Purpose:
   
   Filgotinib (GLPG0634, GS-6034) is an oral, selective JAK1 inhibitor that has demonstrated safety and efficacy data in two 24-week placebo-controlled phase 2B studies as add-on to methotrexate and as monotherapy in active rheumatoid arthritis (RA) patients with inadequate response to MTX (MTX-IR)1,2.
   
   The objective was to evaluate the effect of baseline serum CRP levels on clinical efficacy after 12 weeks of treatment, as assessed by the ACR and DAS28(CRP) subcomponents in MTX-IR RA patients treated with filgotinib.
   
   Methods:
   
   Patients were randomized in a double-blind manner to placebo (PBO) or one of 3 daily doses of filgotinib (50mg, 100mg or 200mg) for 24 weeks. In the DARWIN 1 study, filgotinib on MTX background was evaluated as once (QD) or twice daily treatment. In the DARWIN 2 study once-daily filgotinib was assessed as monotherapy. The inclusion criterion for CRP was amended during the studies and was decreased from 13.5 mg/L to 6.3 mg/L. This post-hoc analysis included patients treated with the selected Phase 3 filgotinib doses, 100mg and 200mg QD, and PBO. Efficacy outcomes were analyzed by baseline CRP level (low: =9 mg/L and high: >9 mg/L, with 9mg/L as ULN).
   
   Results:
   
   Baseline disease activity was high and balanced across the different treatment groups. Comparable baseline values were shown between both CRP subgroups, except for the mean CRP levels (Table 1).
   
   In both low and high CRP subgroups, patients on filgotinib at 100mg or 200mg QD for 12 weeks showed efficacy over PBO, as measured by change from baseline in different subcomponents of the ACR/DAS28(CRP) composite score (TJC68, SJC66, Pt pain, Pt GDA, Inv GDA, HAQ-DI and CRP) (Table 1). In both studies, there was no clear pattern suggesting that baseline CRP level had a consistent effect on filgotinib efficacy.
   
   Conclusion:
   
   This post-hoc analysis of two Phase 2B studies in MTX-IR RA patients suggests that filgotinib treatment once daily at 100mg and 200mg both on the background of MTX and as monotherapy was consistently associated with improved clinical outcomes compared to placebo at Week 12, regardless of baseline CRP levels, as measured by ACR and DAS28(CRP) subcomponents.
   
   References
   
   1Westhovens R, et al. Ann Rheum Dis 2017;76:998-1008; 2Kavanaugh A, et al.Ann Rheum Dis 2017;76:1009-1019.
   
   acrabstracts.org/abstract/no-effect-o...
   
6. NielsjeB 25 september 2017 14:44

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   • NielsjeB

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   ABSTRACT NUMBER: 1458
   Correlation of Multi-Biomarker Disease Activity Score with Clinical Disease Activity Measures for the JAK1-Selective Inhibitor Filgotinib As Monotherapy and in Combination with Methotrexate in Rheumatoid Arthritis Patients
   Mark C. Genovese1, René Galien2, Yang Pan3, Annegret Van der Aa4, Corinne Jamoul4, Pille Harrison4, Chantal Tasset4, Lovely Goyal3, Wanying Li3 and Jacqueline Tarrant3, 1Stanford University Medical Center, Palo Alto, CA, 2Galapagos SASU, Romainville, France, 3Gilead Sciences, Foster City, CA, 4Galapagos NV, Mechelen, Belgium
   
   Background/Purpose: The JAK1 selective inhibitor filgotinib (GLPG0634, GS-6034) was efficacious as both add-on to methotrexate (MTX) and monotherapy in two 24-week phase 2B studies in active rheumatoid arthritis (RA) patients with inadequate response to MTX (DARWIN 1 and 2)1. We evaluated the utility of a Multi Biomarker Disease Activity (MBDA) score in relation to clinical disease activity assessments in patients treated with filgotinib.
   
   Methods: Serum samples from RA patients receiving either a stable dose of MTX and PBO, filgotinib 100mg or 200mg QD (DARWIN 1), or placebo (PBO) or filgotinib monotherapy at 100mg or 200mg once daily (QD, DARWIN 2), were collected and analyzed at baseline and week 12 with the MBDA test (Crescendo Biosciences, CA, US). Spearman’s rank correlations between MBDA score and clinical measures (e.g. DAS28-CRP, SJC28, TJC28) were estimated at baseline and week 12 and for their changes from baseline to week 12.
   
   Results: At baseline, median MBDA scores were the same for both DARWIN 1 and 2 studies (58) with statistically significant correlation observed between MBDA score and DAS28-CRP (r=0.43, r=0.48, respectively, both p<0.001). There was weak correlation of MBDA score with SJC28 and TJC28 for DARWIN 1 (r=0.2, 0.11; p<0.01, ns) and DARWIN 2 (r=0.19, 0.17; both p<0.05). At week 12, statistically significant correlations were observed in 200mg filgotinib monotherapy cohort between MBDA score and DAS28, SJC28, and TJC28 (r=0.6, 0.36, 0.46; p<0.001, <0.01, <0.001) that were less so in 100mg (r=0.33, 0.16, 0.15; p<0.05, ns, ns) and PBO (r=0.49, 0.40, 0.22; p<0.001, <0.01, ns) treatment groups. When comparing change from baseline at week 12, the MBDA only correlated to DAS28-CRP for 200mg filgotinib monotherapy and PBO groups (r=0.36, 0.39; p<0.01). There was no statistically significant correlation between MBDA and clinical measures (or between their changes from baseline) for filgotinib on a background of MTX at week 12.
   
   Conclusion: The MBDA score significantly correlated with disease activity measures in subjects treated with filgotinib as monotherapy for 12 weeks. Despite similar baseline associations and treatment efficacy no correlation was observed between MBDA score and DAS28-CRP for filgotinib with MTX add-on.
   
   References: 1Westhovens R, et al. Ann Rheum Dis 2017; 76: 998-1008; Kavanaugh A, et al. Ann Rheum Dis 2017; 76: 1009–1019.
   
   acrabstracts.org/abstract/correlation...
   
   ABSTRACT NUMBER: 1909
   Long Term Safety of Filgotinib in the Treatment of Rheumatoid Arthritis: Week 84 Data from a Phase 2b Open-Label Extension Study
   Mark C. Genovese1, Arthur Kavanaugh2, Kevin Winthrop3, Maria Greenwald4, Lucia Ponce5, Favio Enriquez Sosa6, Mykola Stanislavchuk7, Minodora Mazur8, Alberto Spindler9, Regina Cseuz10, Natalya Nikulenkova11, Maria Glowacka-Kulesz12, Istvan Szombati13, Anna Dudek14, Neelufar Mozaffarian15, Joy Greer15, Xiao Ding15, Pille Harrison16, Annegret Van der Aa16, René Westhovens17 and Rieke Alten18, 1Stanford University Medical Center, Palo Alto, CA, 2Medicine, University of California, San Diego, La Jolla, CA, 3Oregon Health Sciences University, Portland, OR, 4Desert Medical Advances, Palm Desert, CA, 5Consulta Privada Dra. Lucia Ponce, Temuco, Chile, 6Clinstile SA de CV, Col., Mexico City, Mexico, 7Vinnitsa Regional Clinical Hospital, Vinnitsa, Ukraine, 8IMSP Inst. de Cardiologie, Chisinau, Moldova, The Republic of, 9Centro Médico Privado de Reumatología, Centro Médico Privado de Reumatología, Argentina, 10Revita Reumatologiai Rendelo, Budapest, Hungary, 11Vladimir Reg Clin Hosp, Vladimir, Russian Federation, 12Silesiana Centrum Medyczne, Wroclawska, Poland, 13QUALICLINIC Kft., Budapest, Hungary, 14Centrum Medyczne AMED Warszawa Targówek, Warszawa, Poland, 15Gilead Sciences, Inc, Foster City, CA, 16Galapagos NV, Mechelen, Belgium, 17KU Leuven Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, Leuven, Belgium, 18Internal Medicine, Rheumatology & Clinical Immunology, Schlosspark-Klinik, University Medicine Berlin, Berlin, Germany
   
   Background/Purpose: Filgotinib is an orally administered, selective inhibitor of Janus Kinase 1 (JAK1) currently in Phase 3 development for the treatment of rheumatoid arthritis (RA).
   
   Methods: Previously, two 24-week Phase 2b studies were conducted in subjects with moderately to severely active RA (DARWIN 1, DARWIN 2; Ref 1, 2). Upon completing one of these studies, subjects could receive open-label filgotinib in the DARWIN 3 long-term follow-up study, given as 200 mg QD (100 mg QD for males in the US) or 100 mg BID. This report summarizes safety data from the first dose of filgotinib in DARWIN 1, 2 or 3 until the time that the last subject completed 84 weeks of filgotinib dosing. Efficacy is summarized for all subjects through Week 84 of DARWIN 3.
   
   Results: Ninety percent of subjects (790 of 877) completed the Phase 2b studies, and 739 (84%) enrolled in DARWIN 3; 603 (82%) were female and the mean age was 53 years; 560 completed 84 weeks of filgotinib dosing. When the last subject completed 84 weeks in DARWIN 3, 520 (70.4%) subjects remained on study and 219 (29.6%) had discontinued. Most frequent reasons for discontinuation were positive/indeterminate QuantiFERON (10.3%; no active tuberculosis), protocol specified adverse event (AE) stopping rules (6.8%) and withdrawal of consent (5.8%). Cumulative patient years of exposure (PYE) were 1708 with a median time on study drug of 917 days (range 64 to 1329 days). A summary of safety events and laboratory abnormalities are summarized below. Based on ‘observed case’ analysis, 86%, 69%, and 47% of 560 subjects achieved ACR20/50/70, respectively, and 71% (386/543) achieved DAS28-CRP =3.2.
   
   Conclusion: Filgotinib long-term follow-up data demonstrate a favorable safety and durable efficacy profile in subjects with RA, consistent with prior reports.
   
   References
   
   1. Westhovens R, et al. Ann Rheum Dis 2017;76:998-1008; 2. Kavanaugh A, et al.Ann Rheum Dis 2017;76:1009-1019.
   
   acrabstracts.org/abstract/long-term-s...
7. NielsjeB 25 september 2017 14:45

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   En een bonus-abstract van Gilead over filgotinib:
   
   ABSTRACT NUMBER: 1459
   Lack of Drug-Drug Interaction between Filgotinib, a JAK-1 Selective Inhibitor, and a Representative Hormonal Contraceptive Medication, Levonorgestrel/Ethinyl Estradiol
   Rebecca Begley1, Kacey Anderson2, Timothy R. Watkins1, Jing Shen1, Hao Zheng1, Eugene Vass1, Ann Qin2, Brian P. Kearney2 and Yan Xin2, 1Gilead Sciences, Inc., Foster City, CA, 2Clinical Pharmacology, Gilead Sciences, Inc., Foster City, CA
   
   Background/Purpose:
   
   Filgotinib is a potent and selective JAK1 inhibitor in clinical development for treatment of inflammatory diseases, including rheumatoid arthritis and inflammatory bowel diseases. Filgotinib does not inhibit or induce CYP or UGT metabolic enzymes in vitro, and did not alter the pharmacokinetics (PK) of midazolam, a sensitive CYP3A substrate, in healthy subjects. In order to support the use of filgotinib in fertile women, this Phase I study was conducted to rule out unanticipated interactions of filgotinib on the PK of a representative oral contraceptive (OC), levonorgestrel (LEVO)/ethinyl estradiol (EE).
   
   Methods:
   
   This was an open-label, randomized, two-way crossover study in healthy female subjects. Subjects received a single dose of LEVO (150 ug)/EE (30 ug) alone (Treatment A; reference), or in combination with multiple-dose filgotinib (200 mg once daily; 15 days; Treatment B; test). PK sampling was performed for 120 hours following administration of the OC, and safety was assessed throughout the study. An analysis of variance using a mixed-effects model was applied to the natural logarithmic transformation of PK parameters (AUC and Cmax) for EE and LEVO. Geometric-least squares means (GLSM) ratios and 90% confidence intervals (90%CI) of PK parameters were estimated for the test vs reference treatments, and were compared against pre-specified lack of PK alteration boundaries of 70 to 143%. The PK of filgotinib was evaluated as well, and compared against historical values.
   
   Results:
   
   The study enrolled 24 subjects. All subjects completed study treatments; 1 subject discontinued after the last PK draw, due to withdrawal of consent. The mean (range) age of subjects was 37 (21-45) years, 21 (87.5%) were white, and 24 (100%) were of Hispanic or Latino ethnicity.
   
   Coadministration of OC with filgotinib resulted in comparable exposures of LEVO and EE. The GLSM ratios (90%CI) for AUCinf, AUClast and Cmax of LEVO were 94.9 (90.2, 99.8), 94.2 (89.1, 99.6) and 105 (94.8, 117), respectively; corresponding values for EE were 114 (109, 118), 113 (109, 117) and 114 (106, 122). The GLSM ratios (90%CI) were contained within the pre-specified lack of interaction bounds (70-143%), indicating a lack of interaction of filgotinib on OC. Exposures of filgotinib were consistent with historical data.
   
   Study treatments were generally well tolerated; 3 (12.5%) and 6 (25.0%) of subjects experienced an adverse event (AE) during Treatments A and B, respectively. No serious or severe AEs occurred; all AEs reported were Grade 1 (mild). Of the AEs reported only one (headache) was recorded as related to study drug (during Treatment B), and it was not distinctly attributed to LEVO/EE versus filgotinib. All laboratory abnormalities were Grade 1, and there were no clinically significant trends in laboratory abnormalities, vital sign measurements, or ECG recordings.
   
   Conclusion:
   
   Co-administration with filgotinib did not alter the PK of levonorgestrel/ethinyl estradiol. Hormonal contraceptives can be allowed as an effective contraception method for subjects on filgotinib treatment.
   
   acrabstracts.org/abstract/lack-of-dru...
8. NielsjeB 25 september 2017 14:51

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   En nog een bonus (let op de disclosures):
   
   ABSTRACT NUMBER: 2870
   Ex Vivo Comparison of Baricitinib, Upadacitinib, Filgotinib, and Tofacitinib for Cytokine Signaling in Human Leukocyte Subpopulations
   Iain B. McInnes1, Richard Higgs2, Jonathan Lee2, William L. Macias2, Songqing Na2, Robert A. Ortmann2, Guilherme Rocha2, Thomas Wehrman3, Xin Zhang2, Steven H. Zuckerman2 and Peter C. Taylor4, 1University of Glasgow, Glasgow, United Kingdom, 2Eli Lilly and Company, Indianapolis, IN, 3Primity Bio, Fremont, CA, 4NDORMS, University of Oxford, Oxford, United Kingdom
   
   Background/Purpose: Baricitinib (bari), an oral selective Janus kinase (JAK) 1/2 inhibitor, has been approved in the EU for the treatment of adults with moderately to severely active RA. We compared the in vitro cellular pharmacology of bari to upadacitinib (ABT), filgotinib (filgo), and tofacitinib (tofa), three JAK inhibitors (JAKis) currently approved or in clinical development.
   
   Methods: Peripheral blood mononuclear cells from healthy donors (n=6-12) were incubated with different JAKis over a 7-point concentration range. Following cytokine stimulation, levels of phosphorylated signal transducer and activator of transcription (pSTAT) were measured and IC50 calculated in phenotypically gated leukocyte subpopulations. Therapeutic dose relevance of the in vitro analysis was assessed using calculated mean concentration-time (CT) profiles over 24 h obtained from JAKi-treated subjects (bari 4 mg QD; ABT 15 & 30 mg QD; filgo 100 & 200 mg QD; tofa 5 & 10 mg BID). Time above IC50 (T>IC; h/day) and average daily % inhibition of pSTAT formation (%SI) were calculated for each JAKi, cytokine, and cell type.
   
   Results: The cytokines tested did not signal in all cell types (Table 1). When signaling was detected, IC50, %SI, and T>IC for a particular JAKi were similar across cell types and exhibited dose dependent inhibition (Tables 1 & 2). For JAK1/3 dependent signaling across 4 cytokines (IL-2, 4, 15, 21), IC50 for ABT and tofa were more potent than bari; filgo was the least potent. Overlaid on CT profiles, these results indicated generally higher %SI and longer T>IC for ABT and tofa compared to bari and filgo. For IL-6 (JAK1/2), %SI and T>IC was tofa > bari/ABT > filgo and for IL-10 (JAK1/TYK2), %SI was tofa > bari/ABT > filgo. IFN-? (JAK1/2) was modulated by bari, ABT, and tofa, but not by filgo. IFN-a (JAK1/TYK2) signaling was most potently inhibited with bari and ABT, and less with filgo. Filgo did not appear to modulate GM-CSF signaling (JAK2/2), while %SI and T>IC were similar between bari and ABT.
   
   Conclusion: JAKis display different in vitro pharmacologic profiles which, coupled to their in vivo pharmacokinetics, suggest that they modulate distinct cytokine pathways to differing degrees and durations over 24 h. Bari and filgo inhibited JAK1/3 signaling to a lesser extent than ABT and tofa. Consistent across JAKis, no agent potently or continuously inhibited an individual cytokine signaling pathway throughout the dosing interval as assessed by %SI or T>IC, respectively. These observations may have implications for the varying efficacy and safety profiles observed with JAKis across disease states.
   
   acrabstracts.org/abstract/ex-vivo-com...
9. NielsjeB 25 september 2017 23:30

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   ProQR Announces Positive Top-Line Results from a Phase 1b Study of QR-010 in Subjects with Cystic Fibrosis
   
   ir.proqr-tx.com/phoenix.zhtml?c=25370...
10. [verwijderd] 26 september 2017 18:18

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    Strategies for the etiological therapy of cystic fibrosis
    
    www.nature.com/cdd/journal/vaop/ncurr...
12. HansGarrincha 26 september 2017 18:57

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    quote:

    C200 schreef op 26 september 2017 18:18:

    Strategies for the etiological therapy of cystic fibrosis
    
    www.nature.com/cdd/journal/vaop/ncurr...
    

    Poeh...inhoudelijk zeker...
    En: merci Flosz!
    
    flosz? @floszcrxl 46m46 minutes ago
    
    Strategies for the etiological therapy of cystic fibrosis www.nature.com/cdd/journal/vaop/ncurr... … $VRTX $GLPG etc.
    
13. [verwijderd] 26 september 2017 19:23

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    quote:

    HansGarrincha schreef op 26 september 2017 18:57:

    [...]
    Poeh...inhoudelijk zeker...
    En: merci Flosz!
    
    flosz? @floszcrxl 46m46 minutes ago
    
    Strategies for the etiological therapy of cystic fibrosis www.nature.com/cdd/journal/vaop/ncurr... … $VRTX $GLPG etc.
    
    

    Inderdaad Hans, van Flosz. Die ken ik volgens mij nog wel.
    Een dame uit het Crucell tijdperk. Wel eens op een Crucell meeting ontmoet.
14. voda 26 september 2017 20:13

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    quote:

    C200 schreef op 26 september 2017 19:23:

    [...]
    
    Inderdaad Hans, van Flosz. Die ken ik volgens mij nog wel.
    Een dame uit het Crucell tijdperk. Wel eens op een Crucell meeting ontmoet.
    

    Pardon? Dé Grand Queen van het opzoeken van data en PB'S. Nooit meer zo'n vrouw meegemaakt die ook maar een x% in de buurt komt.
    
    Groet, de andere Hans. :-)
15. Nash equilibrium 27 september 2017 07:53

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    Galapagos and MorphoSys report first promising signs of clinical activity in a Phase 1 study with IL-17C antibody MOR106 in atopic dermatitis patients
    
    27 September 2017 at 07:30 CET
    Generally well-tolerated with no clinically relevant safety signals in Phase 1 study
    At the highest dose level, 5 out of 6 patients (83%) reached an improvement of at least 50% in atopic dermatitis symptoms (EASI-50) by week 4
16. [verwijderd] 27 september 2017 08:02

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    Galapagos and MorphoSys report first promising signs of clinical activity in a Phase 1 study with IL-17C antibody MOR106 in atopic dermatitis patients
    
    27 September 2017 at 07:30 CET
    Generally well-tolerated with no clinically relevant safety signals in Phase 1 study
    At the highest dose level, 5 out of 6 patients (83%) reached an improvement of at least 50% in atopic dermatitis symptoms (EASI-50) by week 4
    Results support progression to Phase 2 study
    GLPG's 3rd novel mechanism to show promising patient results
    MOR106 is the first human monoclonal antibody against IL-17C in clinical development worldwide
    Mechelen, Belgium and Planegg/Munich, Germany; 27 September 2017; 7.30 CET -Galapagos NV (Euronext & NASDAQ: GLPG) and MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) today announced Phase 1 results with their joint investigational antibody program MOR106 directed against IL-17C in patients with moderate-to-severe atopic dermatitis (AD). MOR106 was generated using MorphoSys's Ylanthia antibody platform and is based on a target discovered by Galapagos. IL-17C is a cytokine which has been related to dermal inflammation and shown to be distinct from other members of the IL-17 cytokine family.
    
    The Phase 1 study was a randomized, double-blind, placebo-controlled trial, evaluating single ascending doses (SAD) in healthy volunteers, and multiple ascending doses (MAD) in patients with moderate-to-severe atopic dermatitis. MOR106 was administered as an intravenous infusion. The primary objective of the Phase 1 study was to evaluate the safety and tolerability of MOR106. The study's secondary objective was to characterize the pharmacokinetic (PK) profile of MOR106 in patients. Exploratory objectives to measure early signs of efficacy were also included in the MAD part of the study. 24 patients, diagnosed with moderate-to-severe atopic dermatitis, received four weekly infusions of either placebo or MOR106 in a 1 to 3 ratio of placebo to MOR106. Patients were followed for 11 weeks after the last infusion.
    
    Galapagos and MorphoSys previously disclosed that the SAD "healthy volunteer" part of the Phase 1 study reported generally favorable safety findings. In the MAD portion in patients, all adverse drug reactions observed were mild-to-moderate and transient in nature and did not lead to clinically relevant safety signals. No serious adverse events (SAEs) and no infusion-related reactions (IRRs) were recorded. MOR106 reported a favorable PK profile with dose-dependent exposure and a half-life in patients in line with what was observed in healthy volunteers.
    
    Even though the study was not statistically powered to show differences in efficacy between treatment groups, at the highest dose level of MOR106, in 83% of patients (5 out of 6) an improvement of at least 50% in signs and symptoms of atopic dermatitis measured by the Eczema Area and Severity Index (EASI-50) was recorded at week 4. The onset of activity was rapid and occurred within few weeks and was maintained for over 2 months after the last treatment. Among patients receiving placebo, in 17% of patients (1 out of 6) an EASI-50 improvement was seen at week 4.
    
    "Moderate-to-severe atopic dermatitis is a chronic, debilitating disease affecting millions of patients worldwide with a clear unmet medical need for safe and efficacious treatments. In this Phase 1 study MOR106 was observed to be generally well-tolerated, with a favorable PK profile. In addition, we have seen first very promising signs of clinical activity, with a response sustained for months after stopping treatment," said Professor Diamant Thaçi MD, Direktor Institut für Entzündungsmedizin Universitätsklinikum Schleswig-Holstein Campus Lübeck and Independent Advisor for the study. "There is plenty of room in the clinicians' armamentarium for new treatments in this field, so I very much look forward to working further on the evaluation of this investigational compound and its potential role in treating atopic dermatitis."
    
    "Following JAK1 and autotaxin, IL-17C is the third mechanism out of our proprietary target discovery platform for which we are excited to pursue clinical development, underlining extracellular mechanisms of action as a new area of development for us," said Dr. Piet Wigerinck, CSO of Galapagos. "We are very pleased with the outcome of this initial patient study with the first novel mechanism antibody directed against IL-17C in the Galapagos pipeline. The Phase 1 results of MOR106 support its progression into Phase 2 development in patients. In parallel, we will evaluate the switch to subcutaneous administration."
    
    "We are delighted with these first Phase 1 clinical results from our joint antibody program with Galapagos in patients with moderate-to-severe atopic dermatitis. MOR106 is MorphoSys's fifth program in Morphosys' proprietary development portfolio and the first antibody from our Ylanthia technology platform in the clinic. These data further encourage us to develop MOR106 as a potential novel biologic therapy for patients suffering from this severe disease with high medical need together with our partner Galapagos", commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG.
    
    Galapagos and MorphoSys intend to present the clinical data from this study with MOR106 at a future medical conference.
    
    About Atopic Dermatitis
    Atopic dermatitis, also known as atopic eczema, is a chronic pruritic (itching) inflammatory skin disease that most frequently starts in early childhood, often persists into adulthood, but may also have an adult onset. According to GlobalData, there were 35 million atopic dermatitis patients in the US, the major EU nations and Japan in 2016, approximately 25 million of which were estimated to be moderate-to-severe cases. The main features of atopic dermatitis are the impairment of the skin barrier and dysfunction of the immune system accompanied with dry skin and severe pruritus that is associated with cutaneous hyperactivity to various environmental stimuli. The pruritus (itching) may lead to sleep loss, anxiety, depression and impaired social life and is therefore considered as highest therapeutic need in atopic dermatitis.
    
    About IL-17C
    IL-17C is a cytokine that is broadly expressed in human skin pathologies and is a checkpoint in innate skin immunology, distinct from other members of the IL-17 cytokine family. IL-17c plays a crucial role in human inflammatory conditions, including skin diseases.
    
    About MOR106 and the antibody collaboration
    MOR106 is an investigational human IgG1 monoclonal antibody currently being developed for treatment of inflammatory diseases. It is the first publicly disclosed human monoclonal antibody designed to selectively target IL-17C in clinical development worldwide. MOR106 arises from the strategic discovery and co-development alliance between Galapagos and MorphoSys, in which both companies contribute their core technologies and expertise. Galapagos provides the disease-related biology including cellular assays and targets discovered using its target discovery platform. MorphoSys contributes its Ylanthia antibody technology to generate fully human antibodies directed against the target and contributes full CMC development of this compound. Galapagos and MorphoSys will continue to co-develop MOR106 further in the clinic.
17. avantiavanti 27 september 2017 09:52

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    Morgan Stanley update 27/9
    
    Galapagos NV (GLPG.O)
    Competitive Signal In Initial Atopic Dermatitis Data
    
    Stock Rating Overweight
    Price Target $92.00
    
    Initial signal of 5/6 patients (~83%) with a 50%+ EASI reduction (versus 1/6 in pbo, ~17%) is similar to initial PhIb dupilumab data of 71% versus 19%. IV dosing for MOR106 is a commercial disadvantage, but subq plans are progressing. Clinical pipeline with at least initial data now at 5 compounds.
    Galapagos and partner MorphoSys report initial clinical data with MOR106: The PhI study included 24 patients in 3 cohorts of MOR106 and one placebo group, dosed by IV infusion weekly. The drug was given over 4 weeks with a 10 week follow-up. At the highest dose studied, mgt. indicated that MOR106 achieved an 83% (5/6) reduction in EASI 50%+ while placebo only achieved 17% (1/6). The efficacy was maintained through week 14. The study was not powered for statistical significance. Mgt. indicated that the drug was tolerable and safe, but no specific AEs were given.
    
    Signal appears similar to initial dupilumab Ph1b data: Initial dupilumab data from March 2013 (here) demonstrated a similar signal of 71% EASI 50%+ reduction (19% placebo) versus the 83% for MOR106 and 17% placebo. Importantly, dupilumab data included ~70 patients over 3 cohorts, compared to 24 for MOR106 generating a more robust signal. That said, the MOR106 data suggests a potentially competitive profile, except the inferior IV dosing (dupilumab is subq); however, mgt. has indicated that MOR106 is suitable for subq dosing and reformulation work is ongoing. We await detailed safety data and the PhII plan, but see this as another promising target in Galapagos' portfolio. We would expect GLPG to be up modestly (~5%) on today's news.
    
    
18. avantiavanti 27 september 2017 09:56

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    DeGroof Petercam update 27/9
    
    Galapagos (Buy) - MOR106 shows promising Phase I results (EUR 83 / TP EUR 96)
    
    Facts –Preliminary signs of efficacy
    
    Galapagos and partner MorphoSys reported results from the Phase I study with MOR106 in atopic dermatitis, a chronic inflammatory skin disease.
    The study was a randomized, double-blind, placebo-controlled trial, evaluating single ascending doses in healthy volunteers (56 patients), and multiple ascending doses in patients with moderate-to-severe atopic dermatitis (24 patients).
    
    The primary objective of this study was to evaluate the safety and tolerability of MOR106. The study’s secondary objective was to characterize the pharmacokinetic profile of MOR106 in patients.
    Exploratory objectives to measure early signs of efficacy were also included in the MAD part of the study. Here, 24 patients received four weekly infusions of either placebo or MOR106 in a 1 to 3 ratio.
    MOR106 was shown to be generally well-tolerated with no clinically relevant safety signals.
    
    At the highest dose level, 5 out of 6 patients (83%) reached an improvement of at least 50% in atopic dermatitis symptoms (EASI-50) by week 4.
    
    Our view – Third novel mechanism of action from discovery platform
    MOR106, the first human monoclonal antibody against IL-17C in clinical development, was designed by MorphoSys on their Ylanthia platform. The target represents the third novel mode of action discovered by Galapagos. This again demonstrates the great value that lies within Galapagos’ proprietary discovery platform.
    
    The antibody was previously shown to be well-tolerated in healthy volunteers and this has now been confirmed in atopic dermatitis patients. The preliminary efficacy results seem promising and are in line with what we were expecting (>40% EASI-50, placebo-corrected), with 83% of patients reaching EASI-50 in the highest dose level (vs. 17% placebo). This compares to 59% for dupilumab (vs. 19% placebo), the FDA-approved anti-IL-4/IL-13 antibody marketed by Regeneron.
    
    The data have convinced Galapagos and MorphoSys to go ahead with the clinical development and prepare for submission of the protocol for a large Phase II study in Q4 2017. In addition, the companies are evaluating the switch to subcutaneous administration, which is ready today, but will likely not yet be included in the next Phase II trial.
    
    Investment conclusion
    While still involving a small number of patients, the Phase I results give a first indication of efficacy. We await the full data set, which will be presented at an upcoming conference, to be able to fully evaluate the trial and the competitive advantages of MOR106. At this stage, MOR106 represents EUR 3.2 of our EUR 96 TP. The main weight of our valuation still results from filgotinib, currently in several Phase II and Phase III trials for the treatment of autoimmune diseases. We reiterate our Buy recommendation.
19. [verwijderd] 27 september 2017 10:56

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    quote:

    avantiavanti schreef op 27 september 2017 09:52:

    Morgan Stanley update 27/9
    ...
    Signal appears similar to initial dupilumab Ph1b data: Initial dupilumab data from March 2013 (here) demonstrated a similar signal of 71% EASI 50%+ reduction (19% placebo) versus the 83% for MOR106 and 17% placebo. Importantly, dupilumab data included ~70 patients over 3 cohorts, compared to 24 for MOR106 generating a more robust signal. That said, the MOR106 data suggests a potentially competitive profile, except the inferior IV dosing (dupilumab is subq)
    ...
    

    Wellicht is dit de kern van het matige enthousiasme op de beurs voor MOR106.
    Ja, de initiele resultaten zijn goed, want het lijkt safe en goed te werken.
    MAAR er is al een ander antibody voor dezelfde aandoening met een goede werking. En dat dupilumab van Regeneron heeft maar liefst een voorsprong van 4 1/2 jaar. Toelating ervan in USA en Europa in 2017 of 2018.
    
    ALS na phase II trials de resulaten van MOR106 nog steeds beter blijken te zijn en bijwerkingen vergelijkbaar of beter dan dupilumab, en MOR106 ook bij subcutane toedoening het goed blijkt te doen, zal het enthousiasme natuurlijk wel toenemen. Maar dan zijn we wel even verder.
20. [verwijderd] 27 september 2017 11:11

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    Overigens wordt dupilumab door Regeneron ook getest voor (in phase 3)
    asthma, pediatric asthma, pediatric atopic dermatitis, nasal polyps en Eosinophilic esophagitis (phase 2).
    
    Wellicht dus dat MOR106 ook breder ingezet kan worden.
    
    Merknaam voor atopic dermatitis in volwassenen is Dupixent
    www.regeneron.com/dupixent-injection
    
    De FDA heeft Dupixent goedgekeurd in maart 2017. In Europa heeft de CHMP een positieve opinie gegeven in juli 2017 en wordt er daarom een positieve beslissing over markttoegang verwacht.
    
    
21. HansGarrincha 27 september 2017 11:14

    auteur info

    • HansGarrincha

      Lid sinds: 22 mrt 2004

      Laatste bezoek: 04 aug 2023

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    Opvallend is dat MS refereert aan Dupilumab met 71% EASI 50%+ reduction, terwijl DeGroof Petercam het heeft over 59%...
    
    Iemand die hier duidelijkheid kan geven?