`
`(cid:15)(cid:23)(cid:23)(cid:24)(cid:25)(cid:3)(cid:26)(cid:27)(cid:28)(cid:29)(cid:4)(cid:27)(cid:30)(cid:31)(cid:29)(cid:3)(cid:32)(cid:33)(cid:9)(cid:12)(cid:13)(cid:10)(cid:34)(cid:3)(cid:26)(cid:30)(cid:29)(cid:29)(cid:4)(cid:30)(cid:35)(cid:28)(cid:31)(cid:3)(cid:32)(cid:11)(cid:13)(cid:20)(cid:12)(cid:13)(cid:8)(cid:34)(cid:3)(cid:36)(cid:14)(cid:22)(cid:9)(cid:13)(cid:19)(cid:20)(cid:3)(cid:37)(cid:14)(cid:38)(cid:8)(cid:7)(cid:19)(cid:18)(cid:8)(cid:25)(cid:3)(cid:37)(cid:10)(cid:10)(cid:7)(cid:25)(cid:39)(cid:39)(cid:40)(cid:40)(cid:40)(cid:41)(cid:10)(cid:19)(cid:13)(cid:42)(cid:43)(cid:14)(cid:13)(cid:20)(cid:12)(cid:13)(cid:8)(cid:41)(cid:44)(cid:14)(cid:38)(cid:39)(cid:20)(cid:14)(cid:12)(cid:39)(cid:12)(cid:8)(cid:12)(cid:42)(cid:45)(cid:46)
`
`(cid:21)(cid:12)(cid:17)(cid:44)(cid:14)(cid:13)(cid:10)(cid:12)(cid:13)(cid:22)(cid:8)(cid:42)(cid:3)(cid:42)(cid:9)(cid:22)(cid:18)(cid:17)(cid:3)(cid:12)(cid:13)(cid:3)(cid:45)(cid:46)(cid:46)(cid:30)(cid:25)(cid:3)(cid:14)(cid:13)(cid:44)(cid:14)(cid:20)(cid:14)(cid:18)(cid:47)(cid:3)(cid:42)(cid:9)(cid:22)(cid:18)(cid:17)
`
`(cid:48)(cid:14)(cid:49)(cid:8)(cid:9)(cid:10)(cid:3)(cid:50)(cid:12)(cid:20)(cid:20)(cid:12)(cid:19)(cid:38)(cid:17)
`
`(cid:51)(cid:14)(cid:3)(cid:44)(cid:12)(cid:10)(cid:8)(cid:3)(cid:10)(cid:37)(cid:12)(cid:17)(cid:3)(cid:19)(cid:9)(cid:10)(cid:12)(cid:44)(cid:20)(cid:8)(cid:25)(cid:3)(cid:5)(cid:6)(cid:7)(cid:8)(cid:9)(cid:10)(cid:3)(cid:11)(cid:12)(cid:13)(cid:13)(cid:12)(cid:14)(cid:15)(cid:16)(cid:3)(cid:17)(cid:18)(cid:19)(cid:19)(cid:20)(cid:21)(cid:3)(cid:22)(cid:12)(cid:16)(cid:23)(cid:6)(cid:24)(cid:10)(cid:12)(cid:24)(cid:25)(cid:8)(cid:26)(cid:3)(cid:26)(cid:9)(cid:25)(cid:27)(cid:16)(cid:3)(cid:12)(cid:24)(cid:3)(cid:18)(cid:19)(cid:19)(cid:28)(cid:29)(cid:3)(cid:6)(cid:24)(cid:23)(cid:6)(cid:13)(cid:6)(cid:27)(cid:30)(cid:3)(cid:26)(cid:9)(cid:25)(cid:27)(cid:16)(cid:31)(cid:3)(cid:32)(cid:33)(cid:34)(cid:8)(cid:9)(cid:10)
`(cid:35)(cid:34)(cid:12)(cid:24)(cid:12)(cid:6)(cid:24)(cid:3)(cid:6)(cid:24)(cid:3)(cid:36)(cid:24)(cid:37)(cid:8)(cid:16)(cid:10)(cid:12)(cid:27)(cid:14)(cid:10)(cid:12)(cid:6)(cid:24)(cid:14)(cid:13)(cid:3)(cid:22)(cid:9)(cid:25)(cid:27)(cid:16)(cid:31)(cid:3)(cid:38)(cid:28)(cid:29)(cid:38)(cid:18)(cid:31)(cid:3)(cid:38)(cid:28)(cid:39)(cid:38)(cid:4)(cid:38)(cid:20)(cid:38)(cid:40)(cid:31)(cid:3)(cid:22)(cid:35)(cid:36)(cid:29)(cid:3)(cid:38)(cid:19)(cid:41)(cid:38)(cid:42)(cid:38)(cid:28)(cid:43)(cid:38)(cid:44)(cid:42)(cid:45)(cid:44)(cid:28)(cid:20)(cid:19)(cid:20)(cid:19)(cid:18)(cid:45)(cid:40)(cid:42)(cid:28)(cid:44)(cid:28)
`
`(cid:51)(cid:14)(cid:3)(cid:20)(cid:12)(cid:13)(cid:52)(cid:3)(cid:10)(cid:14)(cid:3)(cid:10)(cid:37)(cid:12)(cid:17)(cid:3)(cid:19)(cid:9)(cid:10)(cid:12)(cid:44)(cid:20)(cid:8)(cid:25)(cid:3)(cid:3)(cid:46)(cid:10)(cid:10)(cid:34)(cid:29)(cid:43)(cid:43)(cid:26)(cid:33)(cid:41)(cid:26)(cid:6)(cid:12)(cid:41)(cid:6)(cid:9)(cid:27)(cid:43)(cid:38)(cid:19)(cid:41)(cid:38)(cid:42)(cid:38)(cid:28)(cid:43)(cid:38)(cid:44)(cid:42)(cid:45)(cid:44)(cid:28)(cid:20)(cid:19)(cid:20)(cid:19)(cid:18)(cid:45)(cid:40)(cid:42)(cid:28)(cid:44)(cid:28)
`
`(cid:47)(cid:25)(cid:7)(cid:13)(cid:12)(cid:16)(cid:46)(cid:8)(cid:26)(cid:3)(cid:6)(cid:24)(cid:13)(cid:12)(cid:24)(cid:8)(cid:29)(cid:3)(cid:19)(cid:44)(cid:3)(cid:48)(cid:6)(cid:37)(cid:3)(cid:18)(cid:19)(cid:19)(cid:20)(cid:41)
`
`(cid:49)(cid:25)(cid:7)(cid:15)(cid:12)(cid:10)(cid:3)(cid:30)(cid:6)(cid:25)(cid:9)(cid:3)(cid:14)(cid:9)(cid:10)(cid:12)(cid:23)(cid:13)(cid:8)(cid:3)(cid:10)(cid:6)(cid:3)(cid:10)(cid:46)(cid:12)(cid:16)(cid:3)(cid:50)(cid:6)(cid:25)(cid:9)(cid:24)(cid:14)(cid:13)(cid:3)
`
`(cid:51)(cid:9)(cid:10)(cid:12)(cid:23)(cid:13)(cid:8)(cid:3)(cid:37)(cid:12)(cid:8)(cid:52)(cid:16)(cid:29)(cid:3)(cid:38)(cid:42)(cid:44)
`
`(cid:53)(cid:12)(cid:8)(cid:52)(cid:3)(cid:9)(cid:8)(cid:13)(cid:14)(cid:10)(cid:8)(cid:26)(cid:3)(cid:14)(cid:9)(cid:10)(cid:12)(cid:23)(cid:13)(cid:8)(cid:16)(cid:3)
`
`(cid:54)(cid:12)(cid:10)(cid:12)(cid:24)(cid:27)(cid:3)(cid:14)(cid:9)(cid:10)(cid:12)(cid:23)(cid:13)(cid:8)(cid:16)(cid:29)(cid:3)(cid:44)(cid:3)(cid:53)(cid:12)(cid:8)(cid:52)(cid:3)(cid:23)(cid:12)(cid:10)(cid:12)(cid:24)(cid:27)(cid:3)(cid:14)(cid:9)(cid:10)(cid:12)(cid:23)(cid:13)(cid:8)(cid:16)(cid:3)
`
`(cid:55)(cid:25)(cid:13)(cid:13)(cid:3)(cid:56)(cid:8)(cid:9)(cid:15)(cid:16)(cid:3)(cid:57)(cid:3)(cid:54)(cid:6)(cid:24)(cid:26)(cid:12)(cid:10)(cid:12)(cid:6)(cid:24)(cid:16)(cid:3)(cid:6)(cid:58)(cid:3)(cid:14)(cid:23)(cid:23)(cid:8)(cid:16)(cid:16)(cid:3)(cid:14)(cid:24)(cid:26)(cid:3)(cid:25)(cid:16)(cid:8)(cid:3)(cid:23)(cid:14)(cid:24)(cid:3)(cid:7)(cid:8)(cid:3)(cid:58)(cid:6)(cid:25)(cid:24)(cid:26)(cid:3)(cid:14)(cid:10)
`(cid:46)(cid:10)(cid:10)(cid:34)(cid:29)(cid:43)(cid:43)(cid:52)(cid:52)(cid:52)(cid:41)(cid:10)(cid:14)(cid:24)(cid:26)(cid:58)(cid:6)(cid:24)(cid:13)(cid:12)(cid:24)(cid:8)(cid:41)(cid:23)(cid:6)(cid:15)(cid:43)(cid:14)(cid:23)(cid:10)(cid:12)(cid:6)(cid:24)(cid:43)(cid:50)(cid:6)(cid:25)(cid:9)(cid:24)(cid:14)(cid:13)(cid:36)(cid:24)(cid:58)(cid:6)(cid:9)(cid:15)(cid:14)(cid:10)(cid:12)(cid:6)(cid:24)(cid:59)(cid:50)(cid:6)(cid:25)(cid:9)(cid:24)(cid:14)(cid:13)(cid:54)(cid:6)(cid:26)(cid:8)(cid:60)(cid:12)(cid:8)(cid:12)(cid:26)(cid:18)(cid:19)
`
`AVENTIS EXHIBIT 2195
`Mylan v. Aventis IPR2016-00712
`
`
`
`1. Background
`
`2. Discontinued drugs
`
`3. Expert opinion
`
`
`
`Discontinued Drugs Perspective
`
` Oncologic
`
` Discontinued drugs in 2007:
`oncology drugs
`
` Robert Williams
` Drug Development Offi ce, Cancer Research UK, 61 Lincoln’s Inn Fields, WC2A 3PX, London, UK
`
` This perspective is part of an annual series of papers discussing drugs dropped
`from clinical development in the previous year. Specifically, this paper focuses
`on the 28 oncology drugs discontinued in 2007. Information for this perspective
`was derived from a search of the Pharmaprojects database for drugs discontinued
`after reaching Phase I – III clinical trials.
`
` Keywords: ABJ-789 , Advant , AG-24322 , AG-858 , ATRA , AZD-5896 , CAT-3888 , CAT-5001 ,
` CE-245677 , CEP-7055 , CP-868596 , Epothilone-D , Ethynylcytidine , Exisulind , GMK ,
` Iboctadekin , Neovastat , NS-9 , OSI-461 , Siplizumab , Talotrexin , Telatinib , VX-667
`
` Expert Opin. Investig. Drugs (2008) 17(12):1791-1816
`
` 1. Background
`
` The article titled ‘Discontinued drugs in 2006: oncology drugs’ [1] in 2007
`reported lack of efficacy as the principal reason for failure of drug candidates in
`clinical development for cancer. High attrition rates in clinical development are a
`critical problem for the pharmaceutical and biotechnology industries and recent
`data suggest that in the oncology area candidate failure rates are increasing with a
`paltry 3.2% of drugs entering Phase I actually reaching the market [2] . This snapshot
`report documents those candidates for which development was reported to have
`been terminated in 2007 and provides a brief analysis of the reported data.
`
` 2. Discontinued drugs
`
` 2.1 General overview
` According to the analysis contained in Table 1 , 28 drugs were dropped from the
`oncology development pipeline in 2007. However, 2 of these molecules were
`supportive therapies (HE-2100 and CB-001) and 3 were discontinued for failure
`in clinical trials outside of the oncology area (Incyclinide, Semapimod and Visilizumab).
`These drugs have not been considered further in this analysis. Of the remaining
`23 drugs 9 were dropped in Phase I, 10 in Phase II and 4 in Phase III. In
`keeping with the 2006 analysis a broad range of therapeutic modalities is repre-
`sented in terminated candidates from both large pharma and biotech pipelines.
` Table 2 details the reasons for candidate termination from both the 2006 and
`2007 data sets.
`
` 2.2 Failures in Phase I
` Termination of development was reported for nine compounds in Phase I
`development. Of these drugs five were protein kinase inhibitors (AG-24322,
`CE-245677, CEP-7055, CP-868596 and VX-667). The Aurora kinase inhibitor
`VX-667 failed to meet pharmacokinetic objectives whereas the VEGF receptor
`kinase inhibitor CEP-7055 was reported as not showing activity. Reasons for
`discontinuation of development of AG-24322 (cyclin-dependent kinase or CDK
`inhibitor), CE-245677 (Tie-2 and TRK/B inhibitor) and CP-868596 (platelet-derived
`growth factor or PDGF receptor kinase inhibitor) were not disclosed. Reasons for
`
`
`
`10.1517/13543780802465737 © 2008 Informa UK Ltd ISSN 1354-3784
`All rights reserved: reproduction in whole or in part not permitted
`
`1791
`
`
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`Discontinued drugs in 2007: oncology drugs
`
`specifi c T-cells
`amplifying tumour-
`presentation and
`promoting antigen
`associated antigens,
`exposing tumour-
`immune response,
`systemic antitumour
`induced a complete
`GMCI system also
`angiogenesis. The
`cells and inhibit
`by TK to kill tumour
`was then activated
`oral prodrug, which
`TK, followed by an
`herpes simplex virus
`(AdV-tk) encoding
`adenoviral vector
`local injection of an
`The system involved
`limited resources.
`cancer owing to
`treatment of ovarian
`GMCI system for the
`development of a
`has discontinued
`Advantagene
`
`Novartis, 2006)
`2006; Form 20-F,
`Novartis, 17 May
`cancer (R&D Day,
`the treatment of
`of epothilone B, for
`synthetic derivative
`ABJ-789, a semi-
`development of
`discontinued
`Novartis has
`
`Financial
`
`Unspecifi ed
`
`I
`
`I
`
`reached
`Phase
`
`ngiogenesis inhibitor
`mmunostimulant
`inhibitor
`DNA polymerase
`
` A
`
` I
`
`alpha 1
`(DNA-directed),
`Polymerase
`
`NA-directed
`
` D
`
`stimulant
`Thymidine kinase
`
`Cancer, ovarian
`
`Advantagene
`
`ell cycle inhibitor
`
` C
`
`Mitotic inhibitor
`
`poptosis agonist
`icrotubule stimulant
`
` M
`
` A
`
`Tubulin, beta
`
`antagonistTUBE-
`Tubulin
`
`Cancer
`
`Novartis
`
`otes
`
` N
`
`eason
`
` R
`
`evelopment
`
` D
`
`arget
`
` T
`
`
`
`description
`harmacology
`
` P
`
`ndications
`
` I
`
`(Licensee)
`riginator
`
` O
`
`therapy, Advant
`Ovarian cancer
`
`ABJ-789
`
`rug name
`
` D
`
`able 1 . Discontinued drugs in 2007: oncologic drugs.
`
` T
`
`1792
`
`Expert Opin. Investig. Drugs (2008) 17(12)
`
`
`
`Williams
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`Expert Opin. Investig. Drugs (2008) 17(12)
`
`1793
`
`21 February 2005)
`10 May 2001 &
`Pages, Antigenics,
`(Company Web
`by Antigenics
`under development
`q.v.), were also
`(Oncophage; both
`specifi c HSPPC-96
`and patient-
`derived HSPPC-96
`specifi c. Pathogen-
`rather than patient-
`were disease-specifi c
`virus. The products
`relevant bact eria or
`infected by the
`human cell lines
`are derived from
`2006). The antigens
`10-K, Antigenics,
`other products (Form
`the development of
`CML to focus on
`the treatment of
`and antigen for
`shock protein-70
`a complex of heat
`cells and based on
`patient cancerous
`made from individual
`personalised vaccine
`of AG-858, a
`development
`discontinued
`Antigenics has
`
`Pfi zer, 31 July 2007)
`(Company pipeline,
`treatment of cancer
`AG-24322 for the
`development of
`discontinued
`Pfi zer has
`
`Strategic
`
`Unspecifi ed
`
`II
`
`I
`
`reached
`Phase
`
`otes
`
` N
`
`eason
`
` R
`
`evelopment
`
` D
`
`arget
`
` T
`
`
`
`Unspecifi ed
`
`Immunostimulant
`
`leukaemia
`Cancer and
`
`Antigenics
`
`Unspecifi ed
`
`Cell cycle inhibitor
`
`Unspecifi ed
`
`Pfi zer
`
`description
`harmacology
`
` P
`
`ndications
`
` I
`
`(Licensee)
`riginator
`
` O
`
`AG-858
`
`AG-24322
`
`rug name
`
` D
`
`Table 1. Discontinued drugs in 2007: oncologic drugs (continued).
`
`
`
`
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`Discontinued drugs in 2007: oncology drugs
`
`Cambridge), 2002)
`4th ERBI Conf.,
`2000, Abs 538;
`Ther., Amsterdam,
`New Drugs Cancer
`EORTC-AACR Symp
`(q.v.) (11th NCI-
`temozolomide
`agents such as
`to alkylating
`as a chemosensitiser
`before the merger)
`Research Ventures
`Technology (Cancer
`Cancer Research
`under license from
`being developed
`26 July 2007). It was
`AstraZeneca,
`(Company pipeline,
`solid tumours
`treatment of
`(ATase), for the
`DNA alkyltransferase
`O6-alkylguanine
`DNA repair enzyme
`and inhibitor of the
`pseudosubstrate
`an orally active
`(Patrin; AZD-5896),
`bromothenylguanine
`development of 4-
`has discontinued
`KuDOS (AstraZeneca)
`
`Unspecifi ed
`
`II
`
`DNA methyltransferase
`O-6-methylguanine-
`
`inhibitor
`DNA alkyltransferase
`O6-alkylguanine-
`
`cancer
`and colorectal
`Melanoma
`
`AstraZeneca
`
`reached
`Phase
`
`otes
`
` N
`
`eason
`
` R
`
`evelopment
`
` D
`
`arget
`
` T
`
`description
`harmacology
`
` P
`
`ndications
`
` I
`
`(Licensee)
`riginator
`
` O
`
`N N
`
`Br
`
`S
`
`N
`
`O
`
`N
`
`N
`
`
`
`4-Bromothenylguanine
`
`rug name
`
` D
`
`Table 1. Discontinued drugs in 2007: oncologic drugs (continued).
`
`
`
`1794
`
`Expert Opin. Investig. Drugs (2008) 17(12)
`
`
`
`Williams
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`malignancies
`haematological
`expressing
`range of CD22-
`q.v.) for a broader
`form (CAT-8015;
`second-generation
`developing a
`CAT was also
`1 November 2005).
`Press release, CAT,
`2001, Abs 3765;
`AACR, New Orleans,
`Genencor (92nd
`development by
`previously under
`CD22. It was
`cancers that express
`targets B-cell-derived
`December 2007). It
`AstraZeneca, 7
`Company pipeline,
`November 2005;
`release, CAT, 28
`cancers (Press
`HCL and other
`the treatment of
`exotoxin PE38 for
`Pseudomonas
`conjugated to
`antibody fragment
`disulphide-linked Fv
`consisting of a
`immunotoxin,
`recombinant
`GCR-3888), a
`CAT-3888 (formerly
`development of
`has discontinued
`AstraZeneca)
`Technology (CAT;
`Cambridge Antibody
`
`Unspecifi ed
`
`D22 molecule
`
` C
`
`II
`
`elongation factor 2
`Eukaryotic translation
`
`antagonist
`Protein synthesis
`
`leukaemia
`and
`Lymphoma
`
`AstraZeneca
`
`reached
`Phase
`
`otes
`
` N
`
`eason
`
` R
`
`evelopment
`
` D
`
`arget
`
` T
`
`description
`harmacology
`
` P
`
`ndications
`
` I
`
`(Licensee)
`riginator
`
` O
`
`CAT-3888
`
`rug name
`
` D
`
`Table 1. Discontinued drugs in 2007: oncologic drugs (continued).
`
`
`
`
`
`Expert Opin. Investig. Drugs (2008) 17(12)
`
`1795
`
`
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`Discontinued drugs in 2007: oncology drugs
`
`leading to cell death
`inactivation of EF2,
`ribosylation and
`irreversible ADP
`catalyses the
`and domain III
`pancreatic cancers,
`ovarian and
`mesothelioma,
`overexpressed in
`cell-surface antigen
`mesothelin, a
`fragment targets
`The antibody
`S00929076).
`1 August 2006,
`(Scrip Daily Online,
`bought the project
`however CAT
`by Enzon as SS1P;
`in development
`It was previously
`pancreatic cancer.
`mesothelioma and
`the treatment of
`exotoxin A for
`of Pseudomonas
`domains II and III
`fragment linked to
`of an antibody
`protein consisting
`as SS1P), a fusion
`(formerly known
`of CAT-5001
`development
`has discontinued
`AstraZeneca)
`Technology (CAT;
`Cambridge Antibody
`
`Unspecifi ed
`
`esothelin
`
` M
`
`I
`
`elongation factor 2
`Eukaryotic translation
`
`factor 2 inhibitor
`Translation elongation
`
`Cancer
`
`AstraZeneca
`
`reached
`Phase
`
`otes
`
` N
`
`eason
`
` R
`
`evelopment
`
` D
`
`arget
`
` T
`
`description
`harmacology
`
` P
`
`ndications
`
` I
`
`(Licensee)
`riginator
`
` O
`
`CAT-5001
`
`rug name
`
` D
`
`Table 1. Discontinued drugs in 2007: oncologic drugs (continued).
`
`
`
`1796
`
`Expert Opin. Investig. Drugs (2008) 17(12)
`
`
`
`Williams
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`Unspecifi ed
`
`I
`
`receptor, type 1
`tyrosine kinase,
`Neurotrophic
`
`inhibitor
`rkA tyrosine kinase
`inhibitor
`TIE-2 tyrosine kinase
`
` T
`
`Anticancer
`
`Pfi zer
`
`Cl
`
`N
`
`N
`
`C
`
`Cl
`
`O
`
`N
`
`H H
`
`CE-245677
`
`Pfi zer, 31 July 2007)
`(Company pipeline,
`treatment of cancer
`and TrkA/B, for the
`inhibitor of Tie-2
`active reversible
`CE-245677, an orally
`development of
`discontinued
`Pfi zer has
`
`ViaCell, 2005)
`factors (4th Qtr Res,
`2 Amgen growth
`It incorporates
`15 January 2002).
`Page, ViaCell,
`(Company Web
`technology
`amplifi cation
`proprietary selective
`using ViaCell’s
`selectively amplifi ed
`The stem cells are
`6 February 2007).
`release, ViaCell,
`Phase II trial (Press
`transplant in the
`21 – 28 days post
`of chimerism at
`owing to the lack
`treatment of cancer,
`engraftment in the
`culture product, for
`blood stem cell
`umbilical cord
`of CB-001, an
`development
`discontinued
`ViaCell has
`
`Effi cacy
`
`II
`
`Not applicable
`
`Not applicable
`
`induced injury
`Chemotherapy-
`
`Amgen
`
`reached
`Phase
`
`otes
`
` N
`
`eason
`
` R
`
`evelopment
`
` D
`
`arget
`
` T
`
`description
`harmacology
`
` P
`
`ndications
`
` I
`
`(Licensee)
`riginator
`
` O
`
`CB-001
`
`rug name
`
` D
`
`Table 1. Discontinued drugs in 2007: oncologic drugs (continued).
`
`
`
`
`
`Expert Opin. Investig. Drugs (2008) 17(12)
`
`1797
`
`
`
`Discontinued drugs in 2007: oncology drugs
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`31 July 2007)
`pipeline, Pfi zer,
`cancer (Company
`for the treatment of
`of PDGF receptors,
`orally active inhibitor
`CP-868596, an
`development of
`discontinued
`Pfi zer has
`
`2002, Abs 5347)
`(San Francisco),
`(q.v.) (93rd AACR
`ester of CEP-5214
`- dimethyl glycine
`
` N
`
`fully synthetic N,
`CEP-7055 is the
`VEGFR-1, -2 and -3.
`2006). It inhibits
`Sanofi -Aventis,
`activity (Form 20-F,
`owing to a lack of
`treatment of cancer
`inhibitor, for the
`tyrosine kinase
`orally active VEGFR
`CEP-7055, an
`development of
`discontinued
`Cephalon has
`
`Unspecifi ed
`
`Effi cacy
`
`I
`
`I
`
`polypeptide
`receptor, beta
`growth factor
`latelet-derived
`polypeptide
`receptor, alpha
`growth factor
`Platelet-derived
`
` P
`
`tyrosine kinase)
`(a type III receptor
`receptor
`insert domain
`receptor) kinase
`permeability factor
`factor/vascular
`endothelial growth
`kinase 1 (vascular
`Fms-related tyrosine
`
`inhibitor
`receptor kinase
`growth factor
`Platelet-derived
`
`Anticancer
`
`Pfi zer
`
`ngiogenesis inhibitor
`
` A
`
`kinase inhibitor
`factor receptor-3
`ndothelial growth
`kinase inhibitor
`factor receptor-2
`ndothelial growth
`kinase inhibitor
`factor receptor-1
`Endothelial growth
`
` E
`
` E
`
`Unspecifi ed
`
`Sanofi -Aventis
`
`reached
`Phase
`
`otes
`
` N
`
`eason
`
` R
`
`evelopment
`
` D
`
`arget
`
` T
`
`description
`harmacology
`
` P
`
`ndications
`
` I
`
`(Licensee)
`riginator
`
` O
`
`O
`
`N
`
`N
`
`N
`
`O
`
`O
`
`CP-868596
`
`
`
`O
`
`CEP-7055
`
`rug name
`
` D
`
`Table 1. Discontinued drugs in 2007: oncologic drugs (continued).
`
`
`
`1798
`
`Expert Opin. Investig. Drugs (2008) 17(12)
`
`
`
`Williams
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`Abs 3183 & 4145)
`New Orleans, 1998,
`89th AACR,
`(as with 5-FU;
`incorporation
`processing after
`and not RNA
`intranuclear pre-RNA)
`(production of
`of RNA biosynthesis
`action was inhibition
`2006). Its principal
`(Ann Rep, GSK,
`anticancer agent
`ribonucleoside
`(TAS-106), a
`ethynylcytidine
`development of
`discontinued
`Taiho has
`
`2001, San Diego)
`biosynthesis (BIO
`toxic epothilone B
`in the pathway for
`genetically blocked
`cellulosum strain
`by a Sorangium
`It was produced
`27 February 2007).
`Roche & Kosan,
`(Press release,
`of KOS-1584 (q.v.)
`tumours, in favour
`paclitaxel-resistant
`for the treatment of
`bacterial product
`epothilone D, a
`development of
`has discontinued
`Kosan Biosciences
`
`Unspecifi ed
`
`II
`
`Unspecifi ed
`
`inhibitor
`RNA synthesis
`
`GlaxoSmithKlineCancer
`
`Strategic
`
`II
`
`Tubulin, beta
`
`Microtubule stimulant
`
`Cancer
`
`ell cycle inhibitor
`itotic inhibitor
`
` M
`
` C
`
`Roche
`Hoffmann-La
`
`reached
`Phase
`
`otes
`
` N
`
`eason
`
` R
`
`evelopment
`
` D
`
`arget
`
` T
`
`description
`harmacology
`
` P
`
`ndications
`
` I
`
`(Licensee)
`riginator
`
` O
`
`O
`
`N
`
`N
`
`N
`
`O
`
`O
`
`O
`
`O
`
`Ethynylcytidine
`
`O
`
`O
`
`O
`
`O
`
`O
`
`S N
`
`Kosan
`Epothilone D,
`
`rug name
`
` D
`
`Table 1. Discontinued drugs in 2007: oncologic drugs (continued).
`
`
`
`
`
`Expert Opin. Investig. Drugs (2008) 17(12)
`
`1799
`
`
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`Discontinued drugs in 2007: oncology drugs
`
`under development
`of exisulind, was also
`CP-246, an analogue
`October 2000).
`Pathways, 13
`release, Cell
`properties (Press
`shows antiangiogenic
`1331 & 1533). It also
`Orleans, 1998, Abs
`89th AACR, New
`December 1995;
`communication,
`activity (Company
`or antiprostaglandin
`on cell proliferation
`a negligible effect
`cycle arrest and has
`induction and cell
`independently of p53
`inducing apoptosis
`carcinogenesis by
`OSI, 2006). It inhibits
`2000; Form 10-K,
`& 13 September
`13 January 1999
`Pathways,
`releases, Cell
`patients (Press
`polyps in FAP
`precancerous colon
`monotherapy for
`therapies and as
`combination
`part of anticancer
`V and II inhibitor, as
`phosphodiesterase
`of exisulind, a
`development
`has discontinued
`the acquisition)
`(Cell Pathways before
`OSI Pharmaceuticals
`
`Unspecifi ed
`
`III
`
`5A, cGMP-specifi c
`Phosphodiesterase
`
`reached
`Phase
`
`otes
`
` N
`
`eason
`
` R
`
`evelopment
`
` D
`
`arget
`
` T
`
`
`
`poptosis agonist
`
` A
`
`inhibitor
`hosphodiesterase II
`inhibitor
`Phosphodiesterase V
`
` P
`
`Cancer
`
`Paladin Labs
`
`description
`harmacology
`
` P
`
`ndications
`
` I
`
`(Licensee)
`riginator
`
` O
`
`O
`
`O
`
`F
`
`
`
`O
`
`S
`
`O
`
`Exisulind
`
`rug name
`
` D
`
`Table 1. Discontinued drugs in 2007: oncologic drugs (continued).
`
`1800
`
`Expert Opin. Investig. Drugs (2008) 17(12)
`
`
`
`Williams
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`2156, 19)
`(Scrip, 1997,
`for other cancers
`under development
`MGV (q.v.), was also
`conjugate vaccine,
`second ganglioside
`the vaccine. A
`technology for
`to the production
`worldwide license
`had an exclusive
`Progenics also
`the agreement,
`(q.v.). Under
`QS-21 adjuvant
`with Antigenics’
`and formulated
`a carrier protein
`cells, coupled to
`95% of melanoma
`which is present in ∼
`GM2 ganglioside,
`It comprised the
`8 August 2007).
`release, Progenics,
`Phase III trials (Press
`lack of effi cacy in
`the US, owing to
`New York, NY,
`Cancer Center,
`Sloan-Kettering
`from Memorial
`vaccine licensed
`conjugate melanoma
`GMK, a ganglioside
`development of
`has discontinued
`Pharmaceuticals
`Progenics
`
`Effi cacy
`
`III
`
`Unspecifi ed
`
`Immunostimulant
`
`Cancer
`
`Pharmaceuticals
`Progenics
`
`reached
`Phase
`
`otes
`
` N
`
`eason
`
` R
`
`evelopment
`
` D
`
`arget
`
` T
`
`description
`harmacology
`
` P
`
`ndications
`
` I
`
`(Licensee)
`riginator
`
` O
`
`GMK
`
`rug name
`
` D
`
`Table 1. Discontinued drugs in 2007: oncologic drugs (continued).
`
`
`
`
`
`Expert Opin. Investig. Drugs (2008) 17(12)
`
`1801
`
`
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`Discontinued drugs in 2007: oncology drugs
`
`contract, and
`advance purchase
`these without an
`prepared to fund
`Hollis-Eden was not
`trials were requested.
`safety and effi cacy
`large-scale pivotal
`not suffi cient, and
`authorisation was
`for emergency use
`previously required
`the limited data
`was decided that
`Human Services, it
`of Health and
`US Department
`meeting with the
`government. In a
`tender by the US
`procurement
`Project BioShield
`of the entire
`cancellation
`from ARS following
`of bone marrow
`for the protection
`HE-2100 (Neumune)
`development of
`discontinued
`Hollis-Eden has
`
`Financial
`
`I
`
`Unspecifi ed
`
`reached
`Phase
`
`otes
`
` N
`
`eason
`
` R
`
`evelopment
`
` D
`
`arget
`
` T
`
`
`
`activity
`pharmacological
`Unidentifi ed
`
`poisoning
`radiation
`marrow
`For bone
`
`Pharmaceuticals
`Hollis-Eden
`
`description
`harmacology
`
` P
`
`ndications
`
` I
`
`(Licensee)
`riginator
`
` O
`
`HE-2100
`
`rug name
`
` D
`
`Table 1. Discontinued drugs in 2007: oncologic drugs (continued).
`
`1802
`
`Expert Opin. Investig. Drugs (2008) 17(12)
`
`
`
`Williams
`
`antineoplastic drug; TK: Thymidine kinase; UC: Ulcerative colitis; VEGFR: Vascular endothelial growth factor receptor.
`OA: Osteoarthritis; PDGF: Platelet-derived growth factor; PTCL: Peripheral T-cell lymphoma; RA: Rheumatoid arthritis; RCC: Renal cell carcinoma; rhIL-18: Recombinant human interleukin-18; SAAND: Selective apoptotic
`GMCI: Gene-mediated cytotoxic immunotherapy; GvHD: Graft-versus-host disease; HCL: Hairy cell leukaemia; HRPC: Hormone-refractory prostate cancer; IBD: Infl ammatory bowel disease; MMP: Metalloproteinase;
`MD: Age-related macular degeneration; ARS: Acute radiation syndrome; CML: Chronic myelogenous leukaemia; CTCL: Cutaneous T-cell lymphoma; EF2: Elongation factor 2; FAP: Familial adenomatous polyposis;
`ource: Pharmaprojects, copyright (c) Informa UK Ltd. 2009 [4] .
`
` A
`
` S
`
`2006)
`(Ann Rep, GSK,
`sensitive cancer