Incyte Corporation · NASDAQ:INCY
Incyte — ASCO 2011
19 slides from Incyte's conference presentation, Dec 3, 2011
Slide 1: Results of a Randomized Study of the JAK Inhibitor INC424 (Ruxolitinib) vs BAT in Myelofibrosis
Results of a Randomized Study of the JAK Inhibitor INC424 (Ruxolitinib) Compared With Best Available Therapy (BAT) in Primary Myelofibrosis (PMF), Post‐Polycythemia Vera Myelofibrosis (PPV‐MF) or Post‐Essential Thrombocythemia Myelofibrosis (PET‐MF) Claire Harrison, Jean‐Jacques Kiladjian, Haifa Kat
Slide 2: COMFORT-II Study Design
COMFORT‐II Study Design • Randomized, open‐label, multicenter phase III trial • Patients were stratified based on baseline IPSS risk category1 Patients with PMF, INC424 (ruxolitinib) PPV-MF, or PET‐ 15 or 20 mg oral BID MF with ≥ 2 IPSS Randomize n = 146 risk factors1 N = 219 2:1 Best available ther
Slide 3: COMFORT-II Endpoints
COMFORT‐II Endpoints • Primary endpoint – Proportion of patients achieving ≥ 35% reduction in spleen volume from baseline (BL) at week 48 as measured by MRI (assessed at weeks 12, 24, 36, and 48)* • Key secondary endpoint – Proportion of patients achieving a ≥ 35% reduction in spleen volume from BL
Slide 4: Demographics and Baseline Patient Characteristics
Demographics and Baseline Patient Characteristics Ruxolitinib BAT (n = 146) (n = 73) Age, median (years) 67 66 Male, n (%) 83 (57) 42 (58) Myelofibrosis type, n( %) PMF 77 (53) 39 (53) PPV‐MF 48 (33) 20 (27) PET‐MF 21 (14) 14 (19) High/intermediate‐2 IPSS risk 60% / 40% 59% / 40% JAK2V617F positive,
Slide 5: Patient Treatments on BAT Arm
Patient Treatments on BAT Arm ATC Class BAT (n = 73) n (%) • 49 (67%) patients Antineoplastic agents 37 (51) received one or more Hydroxyurea 34 (47) BAT medications Glucocorticoids 12 (16) • 24 (33%) patients Epoetin alfa 5 ( 7) received no medication Immunomodulators 5 (7) Purine analogs 4 (6) And
Slide 6: Patient Disposition
Patient Disposition Ruxolitinib BAT (n = 146) (n = 73) Patients n (%) n (%) Ongoing in randomized treatment phase 91 (62) 31 (42) Continued in extension† 29 (20) Crossed over to ruxolitinib* 18 (25) Discontinued 26 (18) 24 (33) Discontinued for adverse event(s) 12 (8) 4 (5) †Protocol‐defined disease
Slide 7: COMFORT-II Efficacy Results (ITT)
COMFORT‐II Efficacy Results (ITT) Primary Endpoint Key Secondary Endpoint Ruxolitinib 95% CI: 24.4, 40.2 % With ≥ 35% spleen volume reduction % With ≥ 35% spleen volume reduction Ruxolitinib 95% CI: 21.3, 36.6 P < .0001 P < .0001 28.5% 31.9% n = 41 n = 46 BAT BAT 95% CI: 0.0, 5.0 95% CI: 0.0, 5.0 0
Slide 8: Percent Change From Baseline in Spleen Volume At Week 48
Percent Change From Baseline in Spleen Volume 80 At Week 48 % Change from baseline at week 48 60 Ruxolitinib 40 P < .0001 20 0 ‐20 ‐40 Primary endpoint ‐60 ‐80 Ruxolitinib BAT Best response at any time on study Ruxolitinib BAT ↓ Spleen volume 132 (97%) 35 (56%) ↑ Spleen volume 4 (3%) 28 (44%)
Slide 9: Duration of Spleen Volume Reduction
Duration of Spleen Volume Reduction 1.0 Event* Censored 0.8 Probability 0.6 0.4 0.2 Observed events, n (%): 14 (20.3) Censored events, n (%): 55 (79.7) 0.0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Weeks From Onset Number at Risk 69 65 64 59 52 52 47 35 35 25 6 6 3 • 69 (47.9%) patients achieved a ≥ 35
Slide 10: Change in EORTC QLQ-C30 Scores at Week 48 Compared With Baseline
Change in EORTC QLQ‐C30 Scores at Week 48 Compared With Baseline 15 Ruxolitinib BAT 9.9 10 9.1 Mean change from baseline Improvement 5 3.4 0 n= 66 27 69 28 Worsening ‐5 ‐5.4 ‐10 Global health status/QoL Role functioning ‐15 • Improvements were seen by week 8 and continued through week 48
Slide 11: Change in Select EORTC QLQ-C30 Scores at Week 48 Compared With Baseline
Change in Select EORTC QLQ‐C30 Scores at Week 48 Compared With Baseline* Worsening Improvement 9.5 Appetite loss ‐8.2 6 Insomnia† ‐12.3 4.8 Dyspnea ‐6.3 3 Pain Ruxolitinib (n = 69) ‐1.9 BAT (n = 28) 0.4 Fatigue ‐12.8 15 10 5 0 ‐5 ‐10 ‐15 Mean change from baseline • Improvements were seen by week 8 a
Slide 12: Changes in FACT-Lym Subscale Scores Compared With Baseline Over Time
Changes in FACT‐Lym Subscale Scores Compared With Baseline Over Time n = 112 49 113 42 99 40 67 28 5.9 6.1 6.0 5.7 Ruxolitinib Mean change from baseline BAT Improvement 1.2 0.7 0.3 ‐0.4 Week 8 Week 16 Week 24 Week 48 • Mean change from baseline scores were higher (indicating better QoL) in the ruxol
Slide 13: Progression-Free Survival, Leukemia-Free Survival, and Overall Survival
Progression‐Free Survival, Leukemia‐Free Survival, and Overall Survival Ruxolitinib BAT Log‐rank HR* (n = 146) (n = 73) p‐value (95% CI) Progression‐free survival Event, n (%) 44 (30) 19 (26) 0.46 0.81 (0.47, 1.39) Censored, n (%) 102 (70) 54 (74) Leukemia‐free survival Event, n (%) 6 (4) 4 (5) 0.51
Slide 14: Anemia and Thrombocytopenia
Anemia and Thrombocytopenia Worst Lab Value on Study*,† Grade 1 Grade 2 Grade 3 Grade 4 n (%) n (%) n (%) n (%) Hemoglobin Ruxolitinib (n = 146) 24 (16) 55 (38) 50 (34) 12 (8) BAT (n = 70) 16 (23) 28 (40) 15 (21) 7 (10) Platelet count Ruxolitinib (n = 146) 46 (32) 41 (28) 9 (6) 3 (2) BAT (n = 69) 11
Slide 15: Red Blood Cell Transfusions During the Study
Red Blood Cell Transfusions During the Study Ruxolitinib BAT (n = 146) (n = 73) Patients receiving ≥ 1 PRBC 75 (51%) 28 (38%) transfusion while on treatment, n (%) Units transfused/month, mean 0.86 0.91
Slide 16: Nonhematologic Adverse Events Regardless of Study Drug Relationship
Nonhematologic Adverse Events Regardless of Study Drug Relationship (≥ 10% in Any Group) Ruxolitinib (n= 146) BAT (n = 73) All Grades Grades 3/4 All Grades Grades 3/4 Adverse Event* n (%) n (%) n (%) n (%) Diarrhea 34 (23) 2 (1) 8 (11) 0 Peripheral edema 32 (22) 0 19 (26) 0 Asthenia 24 (16) 2 (1) 7
Slide 17: Conclusions
Conclusions • The study met its primary and key secondary endpoints with statistical significance • Ruxolitinib demonstrated significant and sustained improvement in splenomegaly, disease‐related symptoms, functioning, and QoL • BAT‐treated patients experienced progressive splenomegaly and either no
Slide 18: COMFORT-II countries, sites
COMFORT‐II 9 countries, 56 sites Netherlands: Netherlands: 55 United United Kingdom: Kingdom: 44 Sweden: Sweden: 22 Belgium: Belgium: 10 10 France: France: Germany: 12 Germany: 12 10 10 Spain: Spain: 33 Austria: Austria: 44 Italy: Italy: 66
Slide 19: COMFORT-II Contributing Investigators
COMFORT‐II Contributing Investigators Austria France Italy Heinz Gisslinger, Vienna Jean‐Jacques Kiladjian, Paris Giovanni Barosi, Pavia Richard Greil, Salzburg Jean‐Yves Cahn, Grenoble Carlo Gambacorti‐Passerini, Monza Holger Rumpold, Linz Nathalie Cambier, Lille Francesco Passamonti, Pavia Dominik