Approval, ownership, market structure, and placement on WHO EML for 100 new cancer NMEs on NCI alpha list

KEI research associate Paul Miano has written the following paper: Cancer: Approval, ownership, market structure, and placement on WHO Model Essential Medicines List, for 100 new molecular entities (NMEs) on the NCI alpha list of cancer drugs and vaccines. KEI Research Note 2011:1,

A full copy of the paper is available in PDF format here.

The following is from the introduction (sans footnotes, which are in the PDF version):

Introduction and Summary

This research note presents data on the approval, ownership, market structure and placement on the WHO Model Lists of Essential Medicines new molecular entities (NMEs) approved by the U.S. Food and Drug Administration (FDA) for the treatment of cancer. The examined products, which include both drugs and vaccines, are those included in the U.S. National Cancer Institute (NCI) “alpha list” of cancer drugs. The July 2011 version of the alpha list includes 100 unique molecular entities, as well as a number of new formulations or combinations and chemotherapeutic regimens. Our analysis focuses on the 100 unique molecular entities.

Each of the products was approved by the FDA through one of two mechanisms. For pharmaceutical drugs, products are registered under a New Drug Application (NDA). For biologic products, registration is through a Biologic License Application (BLA).

Among our findings are the following:

1. The role of biologic products has increased

  • 1.1 Of the 100 drugs and vaccines, 79 were registered under New Drug Applications (NDA) and 21 were registered under Biologic License Applications (BLA).
  • 1.2 From January 1, 2000 to July 2011, 15 of 52 products were biologics, or 29 percent of the total.
  • 1.3 For the 48 products registered before 2000, 6 of 48 were biologic, or 12.5 percent of the total.

2. Registrations have increased, and most cancer drugs are relatively new

  • 2.1 Despite an overall decline in the registration of NME products in recent years, there has been a sharp rate of increase in the registration of NME products for the treatment of cancer.
  • 2.2 In the 38 years from 1952 to 1989, there were only 21 NME on the NCI list, an average of .55 per year.
  • 2.3 In the ten year period of 1990 to 1999, the list contains 27 NME cancer products - an average of 2.7 per year.
  • 2.4 In the ten year period of 2000 to 2009, 45 NME cancer products were registered - an average of 4.5 per year.
  • 2.5 For 2010 through the July of 2011, 7 NME products were registered, an average of 4.4 per year.
  • 2.6 More than half (52 of 100) of all cancer NME products were first registered after January 1, 2000.

3. Most drugs are only available from a single supplier

  • 3.1 66 of the 100 products are only available to one FDA approved supplier or a joint venture managing the same brand name, suggesting strong barriers to entry due to intellectual property rights and other factors.
  • 3.2 45 of 79 pharmaceutical drugs (57 percent) do not have competitive suppliers.
  • 3.3 21 of 21 biologic products (100 percent) do not have competitive suppliers.
  • 3.4 For products registered between January 1 2000, and July 2011, 51 of 52 products (98 percent) do not have competitive suppliers.

4. Ownership is concentrated in six countries, and among thirteen companies

  • 4.1 28 companies own or control the sale of the 66 drugs that do not have competitive suppliers.
  • 4.2 13 companies control more than one cancer monopoly, including:
    • GlaxoSmithKline (9), Amgen (5), Novartis (5)
    • 4 each for Sanofi, Bristol Myers Squibb, Celgene and Roche
    • 3 each for Eisai, Merck, Astrazeneca and Eli Lilly, and
    • 2 each for Pfizer and Cephalon
  • 4.3 In terms of nationality, just six countries host the companies that own and control cancer products sold as a monopoly.
  • 4.4 One half (33 of the 66) monopoly products are controlled by firms located in the United States.
  • 4.5 Of the remaining 33 monopoly products 12 are controlled by UK firms, 11 by firms in Switzerland, 5 by firms in Japan, 4 by firms in France and 1 by a firm in Germany.

5. The WHO Model Essential Medicines List excludes all new cancer drugs

  • 5.1 The March 2011, 17th Edition of the WHO Model Essential Medicines List (EML) includes zero products from the NCI alpha list of cancer drugs on its “core” list of the minimum medicine needs for a basic health care-system.
  • 5.2 The 17th Edition of the WHO Model EML includes 20 products from the NCI alpha list on its “complementary” list of “essential medicines for priority diseases.”
  • 5.3 For the 2011 WHO Model EML complementary list, the newest product that is also on the NCI alpha list was registered 15 years ago, in 1996.
  • 5.4 The newest cancer product on the 2002 version of the complementary WHO Model EML was first registered 19 years earlier, in 1983.

Note: These are the 100 "alpha list" drugs and vaccines included the paper:

No INN (generic name) of products on NCI's Alpha List of cancer drugs Originator brand name 1st FDA App No Year 1st approval Date 1st approval
1 Abiraterone Acetate Zytiga 202379 2011 2011/04/28
2 Vandetanib Vandetanib 022405 2011 2011/04/06
3 Ipilimumab Yervoy 125377 2011 2011/03/25
4 Eribulin Mesylate Halaven 201532 2010 2010/11/15
5 Cabazitaxel Jevtana Kit 201023 2010 2010/06/17
6 Denosumab Prolia (Xgeva) 125320 2010 2010/06/01
7 Sipuleucel-T Provenge 125197 2010 2010/04/29
8 Romidepsin Istodax 022393 2009 2009/11/05
9 Ofatumumab Arzerra 125326 2009 2009/10/26
10 Pazopanib Hydrochloride Votrient 022465 2009 2009/10/19
11 Recombinant HPV Bivalent Vaccine Ceravix 125259 2009 2009/10/16
12 Pralatrexate Folotyn 022468 2009 2009/09/24
13 Everolimus Afinitor 022334 2009 2009/03/30
14 Degarelix Firmagon 022201 2008 2008/12/24
15 Plerixafor Mozobil 022311 2008 2008/12/15
16 Eltrombopag Olamine Promacta 022291 2008 2008/11/20
17 Romiplostim Nplate 125268 2008 2008/08/22
18 Bendamustine Hydrochloride Treanda 022249 2008 2008/03/20
19 Nilotinib Tasigna 022068 2007 2007/10/29
20 Ixabepilone Ixempra 022065 2007 2007/10/16
21 Temsirolimus Torisel 022088 2007 2007/05/30
22 Lapatinib Ditosylate Tykerb 022059 2007 2007/03/13
23 Vorinostat Zolinza 021991 2006 2006/10/06
24 Panitumumab Vectibix 125147 2006 2006/09/27
25 Dasatinib Sprycel 021986 2006 2006/06/28
26 Recombinant HPV Quadrivalent Vaccine Gardasil 125126 2006 2006/06/08
27 Decitabine Dacogen 021790 2006 2006/05/02
28 Sunitinib Malate Sutent 021938 2006 2006/01/26
29 Lenalidomide Revlimid 021880 2005 2005/12/27
30 Sorafenib Tosylate Nexavar 021923 2005 2005/12/20
31 Nelarabine Arranon 021877 2005 2005/10/28
32 Clofarabine Clolar 021673 2004 2004/12/28
33 Palifermin Kepivance 125103 2004 2004/12/15
34 Erlotinib Hydrochloride Tarceva 021743 2004 2004/11/18
35 Azacitidine Vidaza 050794 2004 2004/05/19
36 Bevacizumab Avastin 125085 2004 2004/02/26
37 Cetuximab Erbitux 125084 2004 2004/02/12
38 Pemetrexed Disodium Alimta 021462 2004 2004/02/04
39 Palonosetron Hydrochloride Aloxi 021372 2003 2003/07/25
40 Tositumomab (I 131 Iodine Tositumomab) Bexxar 125011 2003 2003/06/27
41 Bortezomib Velcade 021602 2003 2003/05/13
42 Gefitinib Iressa 021399 2003 2003/05/05
43 Aprepitant Emend 021549 2003 2003/03/27
44 Oxaliplatin Eloxatin 021492 2002 2002/08/09
45 Rasburicase Elitek 103946 2002 2002/07/12
46 Fulvestrant Faslodex 021344 2002 2002/04/25
47 Ibritumomab Tiuxetan Zevalin 125019 2002 2002/02/19
48 Zoledronic Acid (aka zoledronate) Zometa 021223 2001 2001/08/20
49 Imatinib Mesylate Gleevec 021335 2001 2001/05/10
50 Alemtuzumab Campth 103948 2001 2001/05/07
51 Arsenic Trioxide Trisenox 021248 2000 2000/09/25
52 Gemtuzumab Ozogamicin Mylotarg 021174 2000 2000/05/17
53 Bexarotene Taragretin 021055 1999 1999/12/29
54 Aminolevulinic Acid Levulan 020965 1999 1999/12/03
55 Exemestane Aromasin 020753 1999 1999/10/21
56 Epirubicin Hydrochloride Ellence 050778 1999 1999/09/15
57 Temozolomide Temodar 021029 1999 1999/08/11
58 Denileukin Diftitox Ontak 103767 1999 1999/02/05
59 Trastuzumab Herceptin 103792 1998 1998/09/25
60 Thalidomide Thalomid 020785 1998 1998/07/16
61 Capecitabine Xeloda 020896 1998 1998/04/30
62 Talc Sclerosol 020587 1997 1997/12/24
63 Raloxifene Hydrochloride Evista 020815 1997 1997/12/09
64 Rituximab Rituxan 103705 1997 1997/11/26
65 Letrozole Femara 020726 1997 1997/07/25
66 Toremifene Fareston 020497 1997 1997/05/29
67 Imiquimod Aldara 020723 1997 1997/02/27
68 Irinotecan Hydrochloride Camptosar 020571 1996 1996/06/14
69 Topotecan Hydrochloride Hycamtin 020671 1996 1996/05/28
70 Gemcitabine Hydrochloride Gemzar 020509 1996 1996/05/15
71 Docetaxel Taxotere 020449 1996 1996/05/14
72 Anastrozole Arimidex 020541 1995 1995/12/27
73 Dexrazoxane Hydrochloride Zinecard 020212 1995 1995/05/26
74 Vinorelbine Tartrate Navelbine 020388 1994 1994/12/23
75 Pegaspargase Oncaspar 103411 1994 1994/02/01
76 Paclitaxel Taxol 020262 1992 1992/12/29
77 Aldesleukin Proleukin 103293 1992 1992/05/05
78 Fludarabine Phosphate Fludara 020038 1991 1991/04/18
79 Filgrastim Neupogen 103353 1991 1991/02/20
80 Carboplatin Paraplatin 019880 1989 1989/03/03
81 Ifosfamide Ifex 019763 1988 1988/12/30
82 Mesna Mesnex 019884 1988 1988/12/30
83 Leuprolide Acetate Lupron 019010 1985 1985/04/09
84 Etoposide Phosphate VePesid 018768 1983 1983/11/10
85 Daunorubicin Hydrochloride Cerubidine 050484 1979 1979/12/19
86 Cisplatin Platinol 018057 1978 1978/12/19
87 Tamoxifen Citrate Nolvadex 017970 1977 1977/12/30
88 Dacarbazine DTIC-DOME 017575 1975 1975/05/27
89 Doxorubicin Hydrochloride Adriamycin RDF 050467 1974 1974/08/07
90 Bleomycin Blenoxane 050443 1973 1973/07/31
91 Procarbazine Hydrochloride Matulane 016785 1969 1969/07/22
92 Cytarabine Cytarabine 016793 1969 1969/06/17
93 Vinblastine Sulfate Velban 012665 1965 1965/11/05
94 Vincristine Sulfate Oncovin 014103 1963 1963/07/20
95 Fluorouracil Fluorouracil 012209 1962 1962/04/25
96 Cyclophosphamide Cytoxan 012141 1959 1959/11/16
97 Chlorambucil Leukeran 010669 1957 1957/03/18
98 Prednisone Meticorten 009766 1955 1955/02/21
99 Methotrexate Methotrexate sodium 008085 1953 1953/12/07
100 Leucovorin Calcium Leucovorin calcium 008107 1952 1952/06/20
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