Srdan (Serge) Verstovsek M.D., Ph.D. Professor of Medicine Department of Leukemia University of...
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Srdan (Serge) Verstovsek M.D., Ph.D. Professor of Medicine Department of Leukemia University of Texas MD Anderson Cancer Center Houston, Texas, USA JAK
Srdan (Serge) Verstovsek M.D., Ph.D. Professor of Medicine
Department of Leukemia University of Texas MD Anderson Cancer
Center Houston, Texas, USA JAK inhibitors and low blood cell
count
Slide 2
JAK inhibitorDiseases and studies CEP701 MF: phase II finished
and I/II (new formulation) ongoing ET/PV: phase II completed
AZD1480MF: phase I finished, development stopped XL019MF: phase I
finished, development stopped NS-018MF: phase I ongoing
BMS-911543MF: phase I/II ongoing LY2784544ET/PV/MF: phase I
finished; MF: phase II ongoing CYT387 MF: phase I/II QD completed;
phase I/II BID completed; phase III planned SB1518MF: phase I/IIx2
completed, phase III ongoing SAR302503/TG101348 MF: phase I/II
completed; phase II completed, phase III completed; phase II second
line ongoing ET/PV: phase II ongoing; PV: phase III planned
INCB018424/Ruxolitinib MF: approved; phase II (low platelets)
ongoing ET/PV: phase II completed; PV: phase III completed
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JAK2 Inhibitor Side Effects from Phase II Studies GI Anemia
Platelets X X X X X X X Neuropathy X
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Ruxolitinib vs. Placebo: COMFORT-I Background
Placebo-controlled, randomized, double-blind, phase III study
Ruxolitinib starting doses: Baseline platelet count 100-20010 9 /L:
15 mg BID Baseline platelet count >20010 9 /L: 20 mg BID Doses
individually titrated based on safety and efficacy Ruxolitinib
treatment significantly reduced spleen size and improved
myelofibrosis (MF_-related symptoms and QoL and was also associated
with a survival advantage relative to placebo 1 Objective To
describe long-term efficacy and safety of ruxolitinib with 1 year
of additional follow-up beyond previously published data Data
cutoff for current analysis: March 1, 2012. 1. Verstovsek S, et al.
N Engl J Med. 2012;366(9):799-807. Verstovsek S, et al. Blood.
2012;120: Abstract 800.
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Patient Disposition at Current Analysis Patients, n (%)
Ruxolitinib (n = 155) Placebo (n = 151) Placebo Ruxolitinib (n=111)
Still on treatment100 (64.5)073 (65.8) Discontinued55 (35.5)40
(26.5)38 (34.2) Crossed over111 (73.5) Primary reasons for
discontinuation Death13 (8.4)10 (6.6)11 (9.9) Adverse event11
(7.1)9 (6.0)7 (6.3) Consent withdrawn9 (5.8)6 (4.0)9 (8.1) Disease
progression12 (7.7)12 (7.9)5 (4.5) Other10 (6.5)3 (2.0)5 (4.5)
Noncompliance with study medication 1 (0.9) All patients receiving
placebo at the primary analysis crossed over or discontinued within
3 months of the primary analysis Median time to crossover: 41.1
weeks Verstovsek S, et al. Blood. 2012;120: Abstract 800.
Slide 6
Incidence of New Onset Grade 3 or 4 Anemia and Thrombocytopenia
Over Time AnemiaThrombocytopenia All patients receiving placebo at
the primary analysis crossed over or discontinued within 3 months
of the primary analysis; therefore, data for patients receiving
placebo is shown for 0