A	B	C	D	E	F	G	H	I	J	K	L	M	N	O	P	Q	R	S	T	U	V	W	X	Y	Z	AA	AB	AC	AD	AE	AF	AG	AH	AI	AJ	AK	AL	AM	AN	AO	AP	AQ	AR	AS	AT	AU	AV	AW	AX	AY	AZ	BA	BB	BC	BD	BE	BF	BG	BH	BI	BJ	BK	BL
1	Main
2		Brand Name	Remicade, fka cA2.
3		Generic Name	infliximab
4		Administration	IV infusion only.
5		Label	Rheumatoid Arthritis, Psoriasis, Ulcerative Colitis, Crohn's Disease, AS, PSA, pediatric Crohn's.
6		IP	2018?? Cabilly II infringement claim by Genentech. JNJ does not pay royalties. August 2014 in EU as per SGP 10-Q. Golimumab replacement strategy.
7			5,641,651, 5,656,272, 5,698,195, 5,698,419, issued 1997 (2017 expiry). 5,753,628 issued 1998. 7,425,330, 7,416,729, 7,404,955, 7,374,761, 7,335,358 issued 2008.
8			Sued ABT over Humira patents and won $1.67bn in June 2009.
9		Side Effects	Boxed warning on TB/opportunistic infection risk along with lymphoma risk due to immunosuppression. Side effects are very rare.
10		Mechanism	TNF-alpha antibody to soluble and transmembrane TNF-alpha. TNF-a induces IL-1 and IL-6, leukocyte migration (by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes).
11			TNF-a also activates neutrophil and eosinophil functional activity, induces acute phase reactants and other liver proteins and tissue degrading enzymes produced by synoviocytes and chrondocytes.
12			Remicade reduces expression of e-selectin, ICAM-1, VCAM-1, IL-8, MCP-1 and MMP-1 and -3.
13			TNF-alpha is a cytokine secreted by monocytes and macrophages, the receptor for which is TNFR1 and TNFR2. TNFR2 does not seem to have important functions.
14		Molecule	IgG1-kappa chimeric antibody, 149kD. Ki 10^10. Human constant region and murine variable region.
15		Pharmacokinetics	Linear dose-concentration relationship. T1/2 = 8.0-9.5d. No systemic accumulation.
16		Economics	MRK markets ex-US, Japan and other Asian countries. JNJ attempting to regain rights through arbitration. Mitsubishi Tanabe has US. Who has China? JNJ reports Canada as international.
17			Export sales to MRK.
18		Competition	Humira (adalimumab - ABT), Enbrel (etanercept - AMGN), Cimzia (certolizumab pegol - UCB). Oral RA drugs nowhere in sight--JAK3 too toxic and p38 ineffective/toxic. PFE JAK3, Anti-CD20s will be the most serious competition.
19		Markets	~1 million mod-severe RA patients, ~3 million psoriasis patients, ~1 million Crohn's patients in the US.
20		Manufacturing	Leiden, The Netherlands was the original site.
21		Usage	Use is about 65% RA, 25% Crohn's and 10% other.
22		Price	$16,000 vs $12,000 for rivals for annual course in RA. Crohn's disease revenue less than RA?
23		Clinical Studies
24			Phase III "ATTRACT" n=428 MTX-refractory Rheumatoid Arthritis
25			MTX+-Remicade 3mg or 10mg/kg at week 0,2,6 and q4w or q8w thereafter. Folic acid and corticosteroids allowed.
26
27			Phase III "ASPIRE" n=1004 MTX-naïve Rheumatoid Arthritis
28			MTX+-Remicade 3mg or 6mg/kg at week 0,2,6 and q8w thereafter. Folic acid and corticosteroids allowed.
29
30						ATTRACT										ASPIRE
31						Placebo		3mg/kg		3mg/kg		10mg/kg		10mg/kg		Placebo		3mg/kg		6mg/kg
32				30 wks				q8w		q4w		q8w		q4w				q8w		q8w
33				ACR20		0.2		0.5		0.5		0.52		0.58
34				ACR50		0.05		0.27		0.29		0.31		0.26
35				ACR70		0		0.08		0.11		0.18		0.11
36
37				54 wks
38				ACR20		0.17		0.42		0.48		0.59		0.59		0.54		0.62		0.66
39				ACR50		0.09		0.21		0.34		0.4		0.38		0.32		0.46		0.5
40				ACR70		0.02		0.11		0.18		0.26		0.19		0.21		0.33		0.37
41
42				Major Response*		0		0.07		0.08		0.15		0.06		0.08		0.12		0.17
43				*70% ACR for 6 consecutive months
44
45			Phase III "ACT-1" Ulcerative Colitis
46
47			Phase III "ACT-2" Ulcerative Colitis
48
49			Phase III "ACCENT-1" Crohn's Disease
50
51			Phase III "ACCENT-2" Crohn's Disease
52
53			Phase III CINEMA - ocrelizumab vs Remicade in patients failing Humira or Enbrel
54
55
56
57
58			Remicade	1999	2000	2001	2002	2003	2004	2005	2006	2007	2008	2009	2010		1Q99	2Q99	3Q99	4Q99	1Q00	2Q00	3Q00	4Q00	1Q01	2Q01	3Q01	4Q01	1Q02	2Q02	3Q02	4Q02	1Q03	2Q03	3Q03	4Q03	1Q04	2Q04	3Q04	4Q04	1Q05	2Q05	3Q05	4Q05	1Q06	2Q06	3Q06	4Q06	1Q07	2Q07	3Q07	4Q07	1Q08	2Q08	3Q08	4Q08	1Q09	2Q09	3Q09	4Q09	1Q10	2Q10	3Q10	4Q10
59			U.S.	97	304	687	1170	1482	1816	2065	2355	2534	2810	3088	3200.74		21	24	23	29	45	78	80	102	120	166	202	203	236	298	293	343	345	366	390	381	411	447	466	493	501	506	524	535	566	595	602	592	600	625	648	661	676	684	778	672	737	771	822	758	780	783	857	780.74
60			Intl	19	66	34	127	248	329	470	0	1	11	20	24.15		0	2	4	13	4	14	11	37	15	5	7	7	9	34	48	36	64	55	54	75	53	92	79	105	76	136	100	157	115	182	0	0	0	0	0	1	2	2	2	5	5	4	6	5	6	6	7	5.15
61			Exports								658	792	927	1196	1492.25																															0	174	188	131	244	171	246	320	200	198	209	286	327	208	375	400	341	365	386.25
62			WW	116	370	721	1297	1730	2145	2535	3013	3327	3748	4304	4717.139999999999		21	26	27	41	49	91	91	139	135	171	209	210	245	332	341	379	409	421	444	456	464	539	545	598	577	642	624	692	681	777	776	780	731	869	819	908	998	886	978	886	1028	1102	1036	1138	1186	1130	1229	1172.1399999999999
63
64			US y/y		2.134020618556701	1.2598684210526314	0.7030567685589519	0.2666666666666666	0.22537112010796223	0.13711453744493385	0.1404358353510895	0.0760084925690021	0.10891870560378858	0.09893238434163698	0.0365090673575128						1.1428571428571428	2.25	2.4782608695652173	2.5172413793103448	1.6666666666666665	1.1282051282051282	1.525	0.9901960784313726	0.9666666666666666	0.7951807228915662	0.45049504950495045	0.6896551724137931	0.4618644067796611	0.22818791946308714	0.33105802047781574	0.11078717201166177	0.19130434782608696	0.22131147540983598	0.19487179487179485	0.29396325459317585	0.21897810218978098	0.1319910514541387	0.1244635193133048	0.0851926977687627	0.12974051896207595	0.1758893280632412	0.14885496183206115	0.1065420560747663	0.060070671378091856	0.050420168067226934	0.07641196013289031	0.11655405405405395	0.1266666666666667	0.09440000000000004	0.2006172839506173	0.016641452344931862	0.09023668639053262	0.1271929824561404	0.05655526992287907	0.12797619047619047	0.05834464043419274	0.015564202334630295	0.04257907542579065	0.030000000000000027
65			ROW y/y		2.473684210526316	-0.48484848484848486	2.735294117647059	0.9527559055118111	0.3266129032258065	0.4285714285714286	0.3999999999999999	0.20516717325227973	0.18284993694829765	0.2963752665245203	0.24703947368421053							6	1.75	1.8461538461538463	2.75	-0.6428571428571428	-0.36363636363636365	-0.8108108108108107	-0.4	5.8	5.857142857142857	4.142857142857143	6.111111111111111	0.6176470588235294	0.125	1.0833333333333335	-0.171875	0.6727272727272726	0.462962962962963	0.3999999999999999	0.4339622641509433	0.4782608695652173	0.26582278481012667	0.49523809523809526	0.513157894736842	0.33823529411764697	0.74	0.197452229299363	0.13913043478260878	0.34065934065934056	-0.017241379310344862	0.31382978723404253	1.4580152671755724	-0.17213114754098358	0.16959064327485374	-0.1336032388663968	-0.09627329192546585	0.6386138613861385	0.07000000000000006	0.7757009345794392	0.39518900343642605	0.048338368580060465	0.7383177570093458	0.030000000000000027
66			WW y/y		2.189655172413793	0.9486486486486487	0.7988904299583912	0.33384734001542027	0.2398843930635839	0.18181818181818188	0.18856015779092705	0.10421506803849989	0.1265404268109407	0.14834578441835644	0.09598977695167266						1.3333333333333335	2.5	2.3703703703703702	2.3902439024390243	1.7551020408163267	0.8791208791208791	1.2967032967032965	0.5107913669064748	0.8148148148148149	0.9415204678362572	0.631578947368421	0.8047619047619048	0.6693877551020408	0.2680722891566265	0.3020527859237536	0.20316622691292885	0.13447432762836176	0.2802850356294537	0.22747747747747749	0.3114035087719298	0.24353448275862077	0.19109461966604813	0.14495412844036704	0.1571906354515049	0.18024263431542464	0.21028037383177578	0.2435897435897436	0.12716763005780352	0.07342143906020548	0.11840411840411846	0.055412371134020644	0.16410256410256419	0.3652530779753762	0.019562715765247374	0.19413919413919412	-0.024229074889867808	0.03006012024048088	0.24379232505643333	0.059304703476482645	0.28442437923250563	0.1536964980544746	0.025408348457350183	0.1862934362934363	0.029999999999999805
67
68			SGP								1240	1648	2118	2202.7200000000003																						0.8355263157894737	0.8857758620689655	0.8293135435992579	0.8550458715596331	0.8244147157190636	0.8682842287694974	0.7881619937694704	0.8397435897435898	0.773121387283237	0.8311306901615272	0.7657657657657657	0.7757731958762887	0.7589743589743589	0.8207934336525308	0.7192174913693901	0.7912087912087912	0.7279735682819384	0.6773547094188377	0.7720090293453724	0.7955010224948875	0.7584650112866818	0.7169260700389105	0.6996370235934665	0.7934362934362934	0.6660808435852372	0.657672849915683	0.6929203539823009	0.6973148901545972	0.6660808435852373
69
70			Remicade								4253	4975	5866	6506.72
71			Enbrel								4331	5275	6276	6589.8
72			Humira								2044	3063	4345	4562.25
73			Total								10628	13313	16487	17658.77
74												0.25263455024463677	0.2384135807105836	0.07107236004124462
75
76			US %	0.8362068965517241	0.8216216216216217	0.9528432732316228	0.9020817270624518	0.8566473988439306	0.8466200466200466	0.814595660749507	0.7816130102887487	0.7616471295461377	0.7497331910352187	0.7174721189591078	0.6785340269739716