scholarly journals Efficacy and safety of filgotinib in combination with methotrexate in Japanese patients with active rheumatoid arthritis who have an inadequate response to methotrexate: Subpopulation analyses of 24-week data of a global phase 3 study (FINCH 1)

2021 ◽  
Author(s):  
Yoshiya Tanaka ◽  
Tsukasa Matsubara ◽  
Tatsuya Atsumi ◽  
Koichi Amano ◽  
Naoki Ishiguro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Japanese Patients ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Once Daily ◽  
American College Of Rheumatology ◽  
Grade 3

ABSTRACT Objectives Evaluate the efficacy and safety of the Janus kinase-1 inhibitor filgotinib in Japanese patients with rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX). Methods Data from 147 Japanese patients in FINCH 1, a 52-week global Phase 3 study, were analysed up to 24 weeks. Patients received once-daily filgotinib 200 or 100 mg, biweekly adalimumab, or placebo, all with stable background MTX. Results In the Japanese population, American College of Rheumatology 20% response rates at Week 12 (primary endpoint) were 77.5%, 65.9%, 53.6%, and 36.8% for filgotinib 200 mg, filgotinib 100 mg, adalimumab, and placebo. Proportions of patients achieving Disease Activity Score with 28 joints <2.6 at Week 24: filgotinib 200 mg, 65.0%; filgotinib 100 mg, 51.2%; adalimumab, 42.9%; and placebo, 5.3%. Incidence rates of serious infections: filgotinib 200 mg, 2.5%; filgotinib 100 mg, 0%; adalimumab, 10.7%; and placebo, 5.3%. Treatment-emergent laboratory abnormalities Grade ≥3 occurred in five (12.5%) filgotinib 200 mg, three (7.3%) filgotinib 100 mg, one (3.6%) adalimumab, and no placebo patients. No deaths were reported among Japanese patients. Conclusions Filgotinib once daily combined with MTX was effective and generally safe and well tolerated up to Week 24 in Japanese patients with RA and inadequate response to MTX.

scholarly journals Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III randomised, double-blind, placebo-controlled trial (RAJ4) in Japan

2019 ◽  
Vol 78 (10) ◽  
pp. 1305-1319 ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Yoshiya Tanaka ◽  
Sakae Tanaka ◽  
Atsushi Kawakami ◽  
Manabu Iwasaki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Japanese Patients ◽  
Janus Kinase ◽  
Phase Iii ◽  
Tolerability Profile ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
Once Daily

ObjectiveTo evaluate the efficacy and safety of the oral Janus kinase (JAK) inhibitor peficitinib versus placebo in Japanese patients with rheumatoid arthritis (RA).MethodsIn this multicentre, double-blind, parallel-group, placebo-controlled phase III study, patients with RA and inadequate response to methotrexate (MTX) were randomised 1:1:1 to placebo, peficitinib 100 mg once daily or peficitinib 150 mg once daily with MTX for 52 weeks. Based on baseline randomisation, at week 12, non-responders receiving placebo were switched to peficitinib until the end of treatment; the remaining patients were switched to peficitinib at week 28. Primary efficacy variables were American College of Rheumatology (ACR)20 response rate at week 12/early termination (ET) and change from baseline in van der Heijde-modified total Sharp score (mTSS) at week 28/ET.Results519 patients were randomised and treated. Significantly more (p<0.001) peficitinib (58.6%, 100 mg; 64.4%, 150 mg) than placebo (21.8%) recipients achieved ACR20 response at week 12/ET. Significantly lower (p<0.001) mean changes from baseline in mTSS at week 28/ET occurred in peficitinib (1.62, 100 mg; 1.03, 150 mg) than placebo (3.37) recipients. Peficitinib was associated with haematological and biochemical parameter changes, and increased incidence of serious infections and herpes zoster-related disease. One death from suicide occurred in a patient in the placebo group after switching to peficitinib 100 mg.ConclusionsIn Japanese patients with RA and inadequate response to MTX, peficitinib demonstrated significant superiority versus placebo in reducing RA symptoms and suppressing joint destruction. Peficitinib had an acceptable safety and tolerability profile, with no new safety signals compared with other JAK inhibitors.Trial registration numberNCT02305849.

scholarly journals Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to conventional DMARDs: a randomised, double-blind, placebo-controlled phase III trial (RAJ3)

2019 ◽  
Vol 78 (10) ◽  
pp. 1320-1332 ◽  
Author(s):  
Yoshiya Tanaka ◽  
Tsutomu Takeuchi ◽  
Sakae Tanaka ◽  
Atsushi Kawakami ◽  
Manabu Iwasaki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Response Rates ◽  
Janus Kinase ◽  
Phase Iii ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
Once Daily ◽  
Conventional Dmards

ObjectivesTo investigate the efficacy and safety of peficitinib, an oral Janus kinase inhibitor, in patients with rheumatoid arthritis (RA).MethodsIn this double-blind phase III study, patients with RA and an inadequate response to prior disease-modifying anti-rheumatic drugs (DMARDs) were randomised to peficitinib 100 mg once daily, peficitinib 150 mg once daily, placebo or open-label etanercept for 52 weeks’ treatment; placebo-treated patients were switched at week 12 to peficitinib 100 or 150 mg once daily. The primary endpoint was American College of Rheumatology (ACR)20 response at week 12/early termination (ET). Secondary endpoints (assessed throughout) included ACR20, ACR50 and ACR70 response, changes from baseline in disease activity scores (DAS)28 and ACR core parameters, adverse events (AEs) and changes in clinical or laboratory measurements.ResultsIn total, 507 patients received treatment. ACR20 response rates at week 12/ET were significantly higher in the peficitinib 100 mg (57.7%) and 150 mg (74.5%) groups versus placebo (30.7%) (p<0.001). ACR50/70 response rates were also higher for both peficitinib doses versus placebo. Improvements in ACR response were maintained until week 52. Changes from baseline in DAS28-C-reactive protein/erythrocyte sedimentation rate and the ACR core set were significantly greater for both peficitinib doses versus placebo at week 12/ET (p<0.001). AE incidence was similar across treatment arms. Incidence of serious infection and herpes zoster-related disease was higher with peficitinib versus placebo, but with no clear dose-dependent increase.ConclusionsIn patients with RA and inadequate response to DMARDs, peficitinib 100 mg once daily or 150 mg once daily was efficacious in reducing RA symptoms and was well tolerated compared with placebo.Trial registration numberNCT02308163.

scholarly journals Efficacy and safety of filgotinib alone and in combination with methotrexate in Japanese patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: Subpopulation analyses of 24-week data of a global phase 3 study (FINCH 3)

2021 ◽  
Author(s):  
Tatsuya Atsumi ◽  
Yoshiya Tanaka ◽  
Tsukasa Matsubara ◽  
Koichi Amano ◽  
Naoki Ishiguro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Event ◽  
Primary Endpoint ◽  
Active Rheumatoid Arthritis ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
American College Of Rheumatology ◽  
Remission Rates ◽  
Event Rates

ABSTRACT Objectives To evaluate the efficacy and safety of filgotinib for Japanese patients with rheumatoid arthritis (RA) and limited or no prior methotrexate (MTX) exposure. Methods Data up to 24 weeks were analysed for 71 Japanese patients from a 52-week global Phase 3 study. Patients with RA and limited or no prior MTX exposure were randomised in a 2:1:1:2 ratio to filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, or MTX. Maximum MTX dose was 15 mg/week. Primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 24. Results Week 24 ACR20 rates in Japanese patients were 82.6%, 90.9%, 83.3%, and 80.0% for filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, and MTX, respectively. Greater ACR20 rates with filgotinib vs MTX occurred at Week 2. Greater proportions receiving filgotinib vs MTX achieved DAS28-CRP &lt;2.6 at Weeks 12 and 24. Adverse event rates were comparable across treatments and between the Japanese and overall populations. Conclusions While Week 24 ACR20 rates were similar, filgotinib provided faster responses and higher remission rates vs MTX. In Japanese patients with RA and limited or no prior MTX exposure, filgotinib was generally well tolerated.

scholarly journals Efficacy and safety of upadacitinib over 84 weeks in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE)

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Hideto Kameda ◽  
Tsutomu Takeuchi ◽  
Kunihiro Yamaoka ◽  
Motohiro Oribe ◽  
Mitsuhiro Kawano ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Japanese Patients ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Dose Rates ◽  
American College Of Rheumatology

Abstract Background The objective of the study was to evaluate the efficacy and safety of upadacitinib over 84 weeks in Japanese patients with active rheumatoid arthritis (RA) and an inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs. Methods All patients completing a 12-week, randomized, double-blind treatment period entered a blinded extension and continued upadacitinib 7.5, 15, or 30 mg once daily (QD), or were switched from placebo to upadacitinib 7.5, 15, or 30 mg QD. Efficacy and safety were assessed over 84 weeks. Results Of 197 randomized patients, 187 (94.9%) completed the 12-week period and entered the blinded extension; 152 (77.2%) patients were ongoing at week 84. At week 84, the proportions of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR20) were 85.7%, 77.6%, and 58.0% with continued upadacitinib 7.5, 15, and 30 mg, respectively (nonresponder imputation), and were similar in patients who had switched from placebo. Favorable response rates were also observed for more stringent measures of response (ACR50/70) and remission (defined by the Disease Activity Score of 28 joints with C-reactive protein, Clinical Disease Activity Index, or Simplified Disease Activity Index). The 15 mg and 30 mg doses of upadacitinib were associated with more rapid and numerically higher initial responses for some measures of disease activity and remission compared with the 7.5 mg dose. Rates of adverse events, infection, opportunistic infection, serious infection, and herpes zoster were lower with upadacitinib 7.5 and 15 mg versus 30 mg. Conclusions Upadacitinib demonstrated sustained efficacy and was well tolerated over 84 weeks in Japanese patients with RA, with upadacitinib 15 mg offering the most favorable benefit–risk profile. Trial registration ClinicalTrials.gov NCT02720523. Registered on March 22, 2016.

scholarly journals POS1054 UPADACITINIB PHARMACOKINETICS AND EXPOSURE-RESPONSE RELATIONSHIPS FOR EFFICACY AND SAFETY IN PSORIATIC ARTHRITIS – ANALYSES OF THE PHASE 3 SELECT-PsA STUDIES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 805.2-806
Author(s):  
E. Muensterman ◽  
B. Engelhardt ◽  
S. Gopalakrishnan ◽  
J. Anderson ◽  
M. E. Mohamed
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Exposure Response ◽  
Serious Infections ◽  
Grade 3 ◽  
Using Data ◽  
Compare Study

Background:Upadacitinib (UPA) is an oral, reversible, JAK inhibitor approved for the treatment of rheumatoid arthritis (RA). The efficacy and safety profile of UPA in psoriatic arthritis (PsA) has been established in the SELECT-PsA program which includes two global Phase 3 studies.Objectives:These analyses characterize UPA pharmacokinetics and exposure-response relationships for efficacy and safety endpoints using data from the SELECT-PsA studies.Methods:The SELECT-PsA program enrolled patients with prior inadequate response (IR) or intolerance to ≥1 non-bDMARD1 (N=1705) and prior IR or intolerance to ≥1 bDMARD2 (N=642). Data from both trials was integrated for patients receiving placebo (PBO), UPA 15mg once daily (QD) and UPA 30mg QD; adalimumab data was excluded from this analysis. UPA pharmacokinetics were characterized in PsA patients using Bayesian population pharmacokinetics analyses and utilizing prior information from analyses in healthy subjects and RA patients. Exposure-response analyses were conducted using logistic regression to characterize the relationships between upadacitinib average plasma concentration during a dosing interval (Cavg) and the percentage of patients achieving ACR20/50/70 at Weeks 12 and 24, static Investigator Global Assessment of psoriasis (sIGA) of 0 or 1 (clear or almost clear) and at least a 2-point improvement from baseline, and PASI75 at Weeks 16 and 24 or experiencing selected clinically relevant safety events through week 24.Results:Analyses were conducted using data from 1694 subjects (for pharmacokinetics) and 1916 subjects (for exposure-response analyses). UPA model-estimated plasma exposures in subjects with PsA who received 15mg and 30mg QD doses were comparable to previously estimated exposures in subjects with RA. Body weight and methotrexate use had no clinically relevant effects on UPA exposures. There was a statistically significant relationship between UPA Cavg and the percentage of subjects who achieved Week 12 ACR50/70, Week 16 sIGA 0/1, and Week 24 sIGA 0/1 (Figure 1). No statistically significant exposure-response relationship was observed for Week 12 ACR20, Week 16 PASI75, or Week 24 ACR20/50/70 or PASI75, indicating that the 15mg QD exposures are approximately at the plateau of response for these endpoints. No statistically significant relationships were observed between upadacitinib Cavg and the percentage of subjects experiencing pneumonia, herpes zoster, hemoglobin < 8 g/dL, Grade ≥3 lymphopenia, Grade ≥3 neutropenia. There was a shallow but statistically significant exposure-response relationships with the occurrence of serious infections and decrease in hemoglobin from baseline (>2 g/dL and >2 g/dL in combination with hemoglobin < lower limit for normal).Figure 1.Observed and Model Predicted Efficacy Responses at Week 12 (for ACR50/70) or at Weeks 16 and Week 24 (for sIGA 0/1) Versus Upadacitinib Plasma ExposuresConclusion:Exposure-response analyses demonstrated that plasma exposures associated with UPA 15 mg QD achieves robust efficacy in subjects with PsA with limited effects on the evaluated safety endpoints. UPA plasma exposures associated with UPA 15 and 30mg QD are predicted to provide similar ACR responses by week 24 while a small additional efficacy benefit with UPA 30mg is predicted for the achievement sIGA 0/1.References:[1]van Vollenhoven R, et al. Monotherapy with Upadacitinib in MTX-naïve Patients with Rheumatoid Arthritis: Results at 48 Weeks from the SELECT-EARLY Study. 2019 EULAR; THU0197[2]Fleischmann R, et al. Safety and Effectiveness of Upadacitinib or Adalimumab in Patients with Rheumatoid Arthritis: Results at 48 weeks from the SELECT-COMPARE Study. 2019 EULAR; FRI0147Disclosure of Interests:Elena Muensterman Shareholder of: AbbVie, Employee of: AbbVie, Benjamin Engelhardt Shareholder of: AbbVie, Employee of: AbbVie, Sathej Gopalakrishnan Shareholder of: AbbVie, Employee of: AbbVie, Jaclyn Anderson Shareholder of: AbbVie, Employee of: AbbVie, Mohamed-Eslam Mohamed Shareholder of: AbbVie, Employee of: AbbVie.

scholarly journals Efficacy and safety of baricitinib in Japanese patients with rheumatoid arthritis: Subgroup analyses of four multinational phase 3 randomized trials

2017 ◽  
Vol 28 (4) ◽  
pp. 583-591 ◽  
Author(s):  
Yoshiya Tanaka ◽  
Tatsuya Atsumi ◽  
Koichi Amano ◽  
Masayoshi Harigai ◽  
Taeko Ishii ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Randomized Trials ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Subgroup Analyses

scholarly journals Baricitinib inhibits structural joint damage progression in patients with rheumatoid arthritis—a comprehensive review

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Paul Emery ◽  
Patrick Durez ◽  
Axel J. Hueber ◽  
Inmaculada de la Torre ◽  
Esbjörn Larsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Janus Kinase ◽  
X Rays ◽  
Phase 3 ◽  
Once Daily ◽  
Positive Effects ◽  
Damage Progression ◽  
Structural Joint

AbstractBaricitinib is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 that has proved effective and well tolerated in the treatment of rheumatoid arthritis (RA) in an extensive programme of clinical studies of patients with moderate-to-severe disease. In a phase 2b dose-ranging study of baricitinib in combination with traditional disease-modifying antirheumatic drugs (DMARDs) in RA patients, magnetic resonance imaging showed that baricitinib 2 mg or 4 mg once daily provided dose-dependent suppression of synovitis, osteitis, erosion and cartilage loss at weeks 12 and 24 versus placebo. These findings correlated with clinical outcomes and were confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM and RA-BUILD) using X-rays to assess structural joint damage. In patients naïve to DMARDs (RA-BEGIN study), baricitinib 4 mg once daily as monotherapy or combined with methotrexate produced smaller mean changes in structural joint damage than methotrexate monotherapy at week 24. Differences versus methotrexate were statistically significant for combined therapy. In patients responding inadequately to methotrexate (RA-BEAM study), baricitinib 4 mg plus background methotrexate significantly inhibited structural joint damage at week 24 versus placebo, and the results were comparable to those observed with adalimumab plus background methotrexate. In patients responding inadequately to conventional synthetic DMARDs (csDMARDs; RA-BUILD study), baricitinib 4 mg again significantly inhibited radiographic progression compared with placebo at week 24. Benefits were also observed with baricitinib 2 mg once daily, but the effects of baricitinib 4 mg were more robust. The positive effects of baricitinib 4 mg on radiographic progression continued over 1 and 2 years in the long-term extension study RA-BEYOND, with similar effects to adalimumab and significantly greater effects than placebo. Findings from the phase 3 studies of patients with RA were supported by preclinical studies, which showed that baricitinib has an osteoprotective effect, increasing mineralisation in bone-forming cells. In conclusion, baricitinib 4 mg once daily inhibits radiographic joint damage progression in patients with moderate-to-severe RA who are naïve to DMARDs or respond inadequately to csDMARDs, including methotrexate, and the beneficial effects are similar to those observed with adalimumab.

SAT0149 EXPOSURE-RESPONSE RELATIONSHIPS FOR EFFICACY AND SAFETY OF FILGOTINIB AND ITS METABOLITE GS-829845 IN SUBJECTS WITH RHEUMATOID ARTHRITIS BASED ON PHASE 2 AND PHASE 3 STUDIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1013-1014
Author(s):  
A. Meng ◽  
K. Anderson ◽  
C. Nelson ◽  
B. Kirby ◽  
L. Ni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Response Rates ◽  
High Response ◽  
Phase 2 ◽  
Phase 3 ◽  
Once Daily ◽  
Exposure Response ◽  
Serious Infections ◽  
Wide Range ◽  
Grade 3

Background:Filgotinib is an orally administered small molecule that provides selective inhibition of JAK1, a signaling molecule that helps drive inflammatory pathways underlying rheumatoid arthritis (RA).Objectives:Exposure-response (ER) analyses were performed for efficacy following completion of Phase 2 studies over a wide range of doses to support evaluation of 200mg and 100 mg once daily in Phase 3 studies. ER analyses were subsequently performed by using Phase 3 efficacy data to support selection of the proposed registrational dose. ER analyses for safety based on pooled Phase 2 and Phase 3 studies were conducted to examine the safety of evaluated doses.Methods:Population PK analyses were conducted to estimate plasma exposures of filgotinib and GS-829845 (major circulating active metabolite of filgotinib) in both Phase 2 (DARWIN 1 and DARWIN 2) and Phase 3 studies (FINCH 1, FINCH 2, and FINCH 3) encompassing a dose range of 25 to 100 mg twice daily and 50 to 200 mg once daily. As both filgotinib and GS-829845 contribute to efficacy via JAK1 inhibition, their exposures were combined into single parameters, AUCeff and Ctau-eff (effective area under the curve and effective concentration at trough, by accounting for relative inhibition potency and molecular weight) in the ER analyses for various efficacy endpoints (e.g ACR20/50/70 responses) at Week 12 and Week 24. The ER analyses for safety endpoints (the 5 most frequent treatment-emergent adverse events [TEAEs] and Grade 3 or 4 laboratory abnormalities, serious TEAEs, and serious infections) were performed separately for filgotinib and GS-829845 exposures to characterize the individual safety profile of each analyte. The 5 evaluated TEAEs were nausea, nasopharyngitis, upper respiratory tract infection, headache, and hypertension; the 5 Grade 3/4 laboratory abnormalities included lymphocytes decrease, glucose increase, phosphate decrease, triacylglycerol lipase increase, and creatine kinase increase.Results:In the ER analyses for efficacy based on Phase 2 studies, high response rates were demonstrated in ACR20/50/70 across all octile groups in subjects with RA receiving filgotinib and the ER supported further evaluation of both 200 mg and 100 mg once daily doses in Phase 3 clinical studies. Similarly, ER relationships based on pooled Phase 3 studies across various endpoints (e.g ACR20/50/70) consistently revealed high response rates across the exposure range for both the filgotinib 200 mg and 100 mg doses. A trend of increasing response with increasing exposure was observed over the exposure range for multiple secondary efficacy endpoints including ACR50 and ACR70 with the effective exposures at filgotinib 200 mg primarily residing on the plateau of the ER curves.Filgotinib was generally well-tolerated with no individual TEAE or Grade 3 or 4 laboratory abnormality > 5% in the filgotinib 200 mg once daily group up to Week 12. No relationships were observed between filgotinib and GS-829845 exposures (AUC0-24 and Cmax) and the most frequent TEAEs, Grade 3/4 laboratory abnormalities, serious TEAEs, or serious infections up to Week 52.Conclusion:ER analyses demonstrate that both the 200 mg and 100 mg once daily filgotinib doses are efficacious in subjects with moderately to severely active RA without clear dose-dependent effects on safety. The trend towards greater efficacy with higher exposures for some secondary endpoints (ACR50 and ACR70) and a lack of exposure-safety relationship supports a dose of 200 mg once daily over 100 mg once daily since it presents the best benefit/risk ratio among the doses tested.Disclosure of Interests: :Amy Meng Shareholder of: Gilead Sciences, Employee of: Gilead, Kacey Anderson Shareholder of: Gilead Sciences, Employee of: Sciences, Cara Nelson Shareholder of: Gilead, Employee of: Gilead, Brian Kirby Shareholder of: Gilead, Employee of: Gilead, Liyun Ni Shareholder of: Gilead, Employee of: Gilead, Shu-Min Chuang Shareholder of: Gilead, Employee of: Gilead, Brian Kearney Shareholder of: Gilead, Employee of: Gilead, Anita Mathias Shareholder of: Gilead, Employee of: Gilead

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