A	B	C	D	E	F	G	H	I	J	K	L	M	N	O
1	Main
2		Brand Name	Jakafi (US), Jakavi (EU), fka INCB18424
3		Generic Name	ruxolitinib
4		Indication	Myelofibrosis, Polycythemia Vera. At one point studied in HRPC, Multiple Myeloma?
5			Myelofibrosis is a bone marrow disorder that results in collagen scarring in the marrow and other characteristics including spleen enlargement as well as anemia.
6			MPD patients have an abnormal accumulation of blood cells in the peripheral blood and bone marrow.
7			Polycythemia versa is excess blood cells, Essential thrombocytosis is excess platelets, Myelofibrosis is fibrosis in the bone marrow and CML is excess white blood cells in the marrow.
8			Primary myelofibrosis patients have myeloproliferation, bone marrow fibrosis, progressive anemia and marked hepatosplenomegaly.
9			"Post-PV" and "Post-ET" patients have PV/ET and have increasingly fibrotic/scarred bone marrow.
10		Incidence	10,000 myelofibrosis patients in the US.
11			65,000-100,000 and 71,000-80,000 prevalence for PV/ET. 20-30% of PV and 2-4% of ET will transform to MF (post-PV/ET). Ma et al 2008.
12		Mechanism	JAK1/2 inhibitor.
13			V617F mutation is acquired in MF patients.
14		Administration	Oral
15		Competition	Pfizer's Xeljanz (fka CP-690,550 (pan-JAK)). TG101209, Revlimid, Avastin, Vertex, Rigel, Cytopia. CEP-701, XL-019. allogeneic SCT, androgens, prednisone, ESAs, danazol, hydroxyurea, Thalidomide.
16			Hydroxyurea results in cytopenia?
17		Economics	100% US, NVS has ex-US rights. INCY has received $260 million in milestones, and is eligible for "tiered double digit" royalties ex-US.
18		IP	USP 7,598,257, filed December 12, 2006, expires 12/24/2027.
19			March 23, 2023 PDUFA for qd formulation
20		Preclinical
21				IC50
22				CYT387	SB1518	Jakafi	TG101348								Company expects < %5 medicaid
23			JAK1	11 nM	1280 nM	2.7 nM	> 50 nM								Expects to provide free drug for 10 to 15% of MF pts with no insurance
24			JAK2	18 nM	23 nM	4.5 nM	3 nM
25			JAK3	155 nM	520 nM	322 nM
26			JAK2 V618F	11 nM	19 nM		3 nM
27
28		Clinical Trials
29			INCY did obtain an SPA for comfort I in July 2009.
30			As of Oct. 27 2011, all 60 sales reps have been hired and trained.
31			Approved Nov. 16
32
33			Phase III COMFORT-1 - December 2010 results
34			Two primary endpoints will be necessary, one of which will be splenomegaly reduction. Degree of reduction is a question.
35			Avoidance of spleen removal is a positive aspect of the drug.
36			42% response rate versus 1% for placebo (p<0.0001)
37			n=309, primary endpt of % pts achieving 35% or greater reduction in spleen volume at Wk 24 as measured by MRI or CT vs placebo
38			secondary endpts also met stat sig, incl Myelofibrosis Symptom Assessment Form Diary
39			safety consistent w prev studies: reversible thrombocytopenia and anemia
40			detailed results at ASH2011 (ph2 results recently published in NEJM)
41			study not powered to detect OS
42
43			Double-blind, placebo controlled
44			% Reduction in spleen volume at week 24
45			< 10%	23/139
46			10% to 35%	51/139
47			>35%	65/139
48
49			41.9% of ttm pts had >35% reduction in spleen size, compared to 0.7% in pbo group.
50
51			45% thrombocytopenia
52			40.4% anemia (11% grade 3/4)
53			24% diarrhea
54			21.0% peripheral edema
55
56			Phase III COMFORT-II - early 2011 results
57			European study, n=219 randomized 2:1 open-label vs best avail tx
58			primary endpt: proportion of pts with >35% reduction spleen volume at Wk 48
59			study not powered to detect OS
60			% pts with >35% decreased in spleen volume (primary endpoint)
61			28% on TTM, versus 0 on control
62			51% of pts received at least 1 red blood cell transfusion on ttm, compared to 38% on control
63			Aes similar to COMFORT 1
64
65			In EORTC-QLQ-C30 (QOL measure), scores for Global health status and Role funtioning were improved.
66
67			Phase III RESPONSE - results expected June 2013
68			global study, n=300 polycythemia vera pts intolerant or resistant to hydroxyurea
69			primary endpt, at Wk 32: proportion of pts (1) absence of protocol-defined phlebotomy eligibility and (2) a 35% or greater reduction fr baseline in spleen volume
70			INCY has SPA
71
72			Phase IIa Rheumatoid Arthritis 28-day - EULAR 2008 report - Initiated October 2007
73			n=48 total patients. N=16 first cohort at 15mg bid and 4 placebo. N=32 is cohort 2 with 5mg, 25mg BID and 50mg QD.
74			n=16, 75%/50%/25%/17% ACR20/50/70/90. Responses seen as early as one week. Placebo was 50%/0%/0%/0%.
75			15mg twice daily dosing.
76			No dose response?
77
78			Phase I/II myelofibrosis - ASCO 2008, EHA 2008
79			Declines in spleen size but thrombocytopenia side effect.
80			n=93, n=43 evaluable, n=27 with 25mg BID, n=12 10mg BID, n=4 qd.
81			70% of 25mg BID had >50% reductions in spleen size. (n=19/27). 42% of the 10mg group had mean spleen reduction >50%.
82			7/27 required dose reduction due to myelosuppression. Reversible thrombocytopenia was managed with dose reduction/interruption.
83			Most responses ocurred within a month.
84			Patients had >50% reduction in symptoms (fatigue, pruritus, night sweats). Patients had significant weight gain but no hematological improvement.
85			Over 100 patients have been enrolled as of Q2 2008.
86			Patients had a median enlarged spleen size of 20cm above the LCM.
87
88			Phase II Polycythemia Vera/Essential Thrombocythemia - Initiated Q2 2008
89			n=100 planned to enroll in an open-label multi-dose study.
90
91			Phase IIa HRPC/Multiple Myeloma study - YE08 results
92
93
94			Phase IIa Psoriasis data - Presented 9/2008
95			Study "201" and "202" showed improvements in total lesion scores similar to the approved therapies Dovenex and Diprolene.
96
97
98			Phase III "REACH3" GvHD
99			50% ORR vs. 26% for BAT at 24 weeks
100
101			Phase III "REACH2" GvHD
102			62% ORR vs. 39% for BAT at day 28