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Top R D Drug Failures Toxicity and Serious Adverse Events in Late Stage Drug Development are the M

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Top R&D Drug Failures - Toxicity and Serious Adverse Events in Late Stage Drug Development are the Major Causes of Drug Failure Summary GBI Research, leading business intelligence provider, has released its latest research report, ‘Top R&D Drug Failures - Toxicity and Serious Adverse Events in Late Stage Drug Development are the Major Causes of Drug Failure’, which provides insights into major drug failures during 2005–2010. The 20 drugs included in the report belong to key pharmaceutical companies and were undergoing research for a major indication. The report also includes the total expenditure of top pharmaceutical companies in R&D throughout 1996–2009, and an analysis of the financial loss faced by such companies when a drug fails in the late stages of development. GBI Research discovered that the economic impact of drug failure during late stage development increased in relation to the escalating cost of development for new therapeutic agents. The main cause of drug failure in Phase III, when the efficacy of the drug is already evaluated, is either its safety measures or its ability to demonstrate any additional benefits in a larger population over a longer time period. Pharmaceutical companies have recently invested substantial amounts of money in R&D processes; in order to combat the threat of patent expires of blockbuster drugs, and to increase the chances of discovering a drug which could generate considerable revenue for the company. If a drug receives approval and is patented, companies’ returns are significantly higher than the amount invested in R&D. The attrition of molecules occurs at various stages of the trial during drug development process. The majority of molecules fail at the initial stages of development, such as pre-clinical studies and Phase I and II. Pharmaceutical companies face huge losses when drugs fail in the late stage of trials, such as Phase III and the post-marketing stage. According to analysis conducted during 2005–

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									         Top R&D Drug Failures - Toxicity and Serious Adverse
         Events in Late Stage Drug Development are the Major
                        Causes of Drug Failure
 Reference Code: GBIHC110MR                                                                                            Publication Date: July 2011


                                    Oncology Dominates with Highest Number of Drug Failures among All Therapy Areas
   The highest number of
   drug failures was                The majority of major drug failures are in the field of oncology, because the number of ongoing
   observed in oncology,            trials is highest for this indication compared to other diseases. Pharmaceutical companies invest
   followed by CNS,                 substantial sums of money in drug development, and sponsor companies only start Phase III trials
   metabolic disorders and          after receiving promising results from preclinical studies and early pivotal studies. In the initial
   anti-infectives.                 phases, clinical trials explore the safety and efficacy of the drug, investigations which do not
                                    necessarily give the same results when tested in a larger population and for longer durations in
                                    Phase III. The results of Phase III also depend on the trial design of the study for that phase. For a
                                    drug to be successful in the trial, it has to demonstrate its efficacy and safety within the regulatory
                                    requirements, in order to achieve approval for marketing.

                                      Top R&D Drug Failures, Drug Failure By Therapy Area (%), 2007–2010

                                                                                Other
                                                                                19%
                                                                                                                       Anti Cancer
                                                                                                                          29%




                                                        Cardiovascular
                                                             8%




                                                              Anti-Infectives
                                                                   13%
                                                                                                                       Nervous System
                                                                                                                            18%


                                                                                   Metabolic Disorder
                                                                                        13%


                                      Source: GBI Research, Nature Reviews



                                    The figure above shows drug failure by various indications during 2007–2010. The highest number
                                    of failures was observed in oncology, due to the fact that the number of trials in this field is higher
                                    than in other fields. The other area of interest for pharmaceutical companies is diseases associated
                                    with the central nervous system, including major diseases such as Alzheimer’s, epilepsy and
                                    multiple sclerosis.




Top R&D Drug Failures - Toxicity and Serious Adverse Events                                                        GBIHC110MR /Published JUL 2011
in Late Stage Drug Development are the Major Causes of Drug
Failure                                                                                                                                        Page 1
                                                                                © GBI Research. This is a licensed product and is not to be photocopied
                                    Lack of Adequate Superiority in Efficacy the Major Reason Related To Drug Failure
                                    The areas of oncology and heart failure are more susceptible to drug failures, as the drugs for
                                    these indications must possess a life saving capacity. Indications related to the central nervous
                                    system, such as Alzheimer’s disease and multiple sclerosis, are also a key area in which major
                                    drugs fail. Due to the complexity of such areas, it is very difficult to find a drug which is appropriate
                                    for approval.

                                      Top R&D Drug Failures, Reasons Related To Drug Failure (%), 2007–2010
                                                                                                   Safety ( Including Risk
                                                                                                          Benefit)
                                                                                                             21%




                                                                                                             Financial /Commercial
                                                                                                                       7%


                                                                                                           Non Disclosed
                                                     Efficacy                                                   6%
                                                      66%




                                      Source: GBI Research, Nature Review



                                    The above figure shows the categories in which major drug failure occurred during 2007–2010. The
                                    highest number of drugs failed when their efficacy was tested in conjunction with a placebo.
                                    Another major section of the drugs failed when their efficacy was compared as an add-on therapy
                                    to the existing approved drug, and when safety parameters were tested, causing drugs to be either
                                    dropped during the trial, or failure at the end.
                                    R&D Expenditure by Major Pharmaceutical Companies
                                    For the last number of years, pharmaceutical companies have been investing significant amounts
                                    in R&D processes, due to the impending patent the patent expiries of their blockbuster drugs and
                                    failing trials. During 1996–2009, Roche accounted for the highest R&D expenditure, followed by
                                    Pfizer, Novartis, J&J and Sanofi. Roche invested $8.7 billion in R&D during 1996–2009, the highest
                                    expenditure of any pharmaceutical company during that period.




Top R&D Drug Failures - Toxicity and Serious Adverse Events                                                    GBIHC110MR /Published JUL 2011
in Late Stage Drug Development are the Major Causes of Drug
Failure                                                                                                                                    Page 2
                                                                            © GBI Research. This is a licensed product and is not to be photocopied
                                    1 Table of Contents
                                    1 Table of Contents ........................................................................................................................ 3
                                      1.1    List of Tables..................................................................................................................... 6
                                      1.2    List of Figures ................................................................................................................... 7
                                    2 Introduction .................................................................................................................................. 8
                                      2.1    Number of Drugs Discontinued From the Pipeline ............................................................ 8
                                      2.2    Number of Drugs Discontinued by Major Pharmaceutical Companies (2005-2010) ......... 9
                                      2.3    R&D Expenditure by Major Pharmaceutical Companies ................................................. 10
                                      2.4    GBI Research Report Guidance ..................................................................................... 11
                                    3 Top Phase III Drug Failures (2005–2010) ................................................................................. 12
                                      3.1    Semagacestat ................................................................................................................. 12
                                         3.1.1    Unmet Need for Indication ....................................................................................... 12
                                         3.1.2    Introduction .............................................................................................................. 13
                                         3.1.3    Clinical Trial Study Details ....................................................................................... 13
                                         3.1.4    Reasons for Failure ................................................................................................. 15
                                      3.2    Zibotentan ....................................................................................................................... 15
                                         3.2.1    Unmet Need for Indication ....................................................................................... 15
                                         3.2.2    Introduction .............................................................................................................. 16
                                         3.2.3    Clinical Trial Study Details ....................................................................................... 16
                                         3.2.4    Reasons for Failure ................................................................................................. 18
                                      3.3    Vicriviroc ......................................................................................................................... 18
                                         3.3.1    Unmet Need for Indication ....................................................................................... 18
                                         3.3.2    Introduction .............................................................................................................. 19
                                         3.3.3    Clinical Trial Study Details ....................................................................................... 19
                                         3.3.4    Reasons for Failure ................................................................................................. 20
                                      3.4    Torcetrapib ...................................................................................................................... 21
                                         3.4.1    Unmet Need for Indication ....................................................................................... 21
                                         3.4.2    Introduction .............................................................................................................. 22
                                         3.4.3    Clinical Trial Study Details ....................................................................................... 22
                                         3.4.4    Reasons for Failure ................................................................................................. 23
                                      3.5    Iniparib ............................................................................................................................ 23
                                         3.5.1    Unmet Need for Indication ....................................................................................... 23
                                         3.5.2    Introduction .............................................................................................................. 24
                                         3.5.3    Clinical Trial Study Details ....................................................................................... 24
                                         3.5.4    Reasons for Failure ................................................................................................. 25
                                      3.6    ASA404 ........................................................................................................................... 26
                                         3.6.1    Unmet Need for Indication ....................................................................................... 26
                                         3.6.2    Introduction .............................................................................................................. 27
                                         3.6.3    Clinical Trial Study Details ....................................................................................... 27
                                         3.6.4    Reasons for Failure ................................................................................................. 28
                                      3.7    Figitumumab ................................................................................................................... 28
                                         3.7.1    Unmet Need for Indication ....................................................................................... 29
                                         3.7.2    Introduction .............................................................................................................. 29
                                         3.7.3    Clinical Trial Study Details ....................................................................................... 29
                                         3.7.4    Reasons for Failure ................................................................................................. 30
                                      3.8    Sutent ............................................................................................................................. 31
                                         3.8.1    Unmet Need for Indication ....................................................................................... 31
                                         3.8.2    Introduction .............................................................................................................. 32
                                         3.8.3    Clinical Trial Study Details ....................................................................................... 32
                                         3.8.4    Reasons for Failure ................................................................................................. 33
                                      3.9    Recentin .......................................................................................................................... 33
                                         3.9.1    Unmet Need for Indication ....................................................................................... 34
                                         3.9.2    Introduction .............................................................................................................. 34
                                         3.9.3    Clinical Trial Study Details ....................................................................................... 34


Top R&D Drug Failures - Toxicity and Serious Adverse Events                                                                            GBIHC110MR /Published JUL 2011
in Late Stage Drug Development are the Major Causes of Drug
Failure                                                                                                                                                                      Page 3
                                                                                       © GBI Research. This is a licensed product and is not to be photocopied
                                           3.9.4  Reasons for Failure ................................................................................................. 35
                                        3.10 Ocrelizumab .................................................................................................................... 35
                                           3.10.1 Unmet Need for Indication ....................................................................................... 36
                                           3.10.2 Introduction .............................................................................................................. 36
                                           3.10.3 Clinical Trial Study Details ....................................................................................... 37
                                           3.10.4 Reasons for Failure ................................................................................................. 38
                                        3.11 GVAX .............................................................................................................................. 39
                                           3.11.1 Unmet Need for Indication ....................................................................................... 39
                                           3.11.2 Introduction .............................................................................................................. 40
                                           3.11.3 Clinical Trial Study Details ....................................................................................... 40
                                           3.11.4 Reasons for Failure ................................................................................................. 41
                                        3.12 Teplizumab ..................................................................................................................... 42
                                           3.12.1 Unmet Need for Indication ....................................................................................... 42
                                           3.12.2 Introduction .............................................................................................................. 43
                                           3.12.3 Clinical Trial Study Details ....................................................................................... 43
                                           3.12.4 Reasons for Failure ................................................................................................. 44
                                        3.13 Taspoglutide ................................................................................................................... 45
                                           3.13.1 Unmet Need for Indication ....................................................................................... 45
                                           3.13.2 Introduction .............................................................................................................. 46
                                           3.13.3 Clinical Trial Study Details ....................................................................................... 46
                                           3.13.4 Reasons for Failure ................................................................................................. 48
                                        3.14 NOV002 .......................................................................................................................... 49
                                           3.14.1 Unmet Need for Indication ....................................................................................... 49
                                           3.14.2 Introduction .............................................................................................................. 49
                                           3.14.3 Clinical Trial Study Details ....................................................................................... 50
                                           3.14.4 Reasons for Failure ................................................................................................. 51
                                        3.15 Otelixizumab ................................................................................................................... 51
                                           3.15.1 Unmet Need for Indication ....................................................................................... 52
                                           3.15.2 Introduction .............................................................................................................. 52
                                           3.15.3 Clinical Trial Study Details ....................................................................................... 52
                                           3.15.4 Reasons for Failure ................................................................................................. 53
                                        3.16 Dimebon.......................................................................................................................... 54
                                           3.16.1 Unmet Need for Indication ....................................................................................... 54
                                           3.16.2 Introduction .............................................................................................................. 55
                                           3.16.3 Clinical Trial Study Details ....................................................................................... 55
                                           3.16.4 Reasons for Failure ................................................................................................. 56
                                        3.17 Avastin ............................................................................................................................ 57
                                           3.17.1 Unmet Need for Indication ....................................................................................... 57
                                           3.17.2 Introduction .............................................................................................................. 58
                                           3.17.3 Clinical Trial Study Details ....................................................................................... 58
                                           3.17.4 Reasons for Failure ................................................................................................. 59
                                        3.18 Aflibercept ....................................................................................................................... 60
                                           3.18.1 Unmet Need for Indication ....................................................................................... 60
                                           3.18.2 Introduction .............................................................................................................. 60
                                           3.18.3 Clinical Trial Study Details ....................................................................................... 61
                                           3.18.4 Reasons for Failure ................................................................................................. 62
                                        3.19 Cladribine ........................................................................................................................ 62
                                           3.19.1 Unmet Need for Indication ....................................................................................... 62
                                           3.19.2 Introduction .............................................................................................................. 63
                                           3.19.3 Clinical Trial Study Details ....................................................................................... 64
                                           3.19.4 Reasons for Failure ................................................................................................. 65
                                        3.20 Rolofylline ....................................................................................................................... 65
                                           3.20.1 Unmet Need for Indication ....................................................................................... 65
                                           3.20.2 Introduction .............................................................................................................. 66
                                           3.20.3 Clinical Trial Study Details ....................................................................................... 66

Top R&D Drug Failures - Toxicity and Serious Adverse Events                                                                          GBIHC110MR /Published JUL 2011
in Late Stage Drug Development are the Major Causes of Drug
Failure                                                                                                                                                                   Page 4
                                                                                      © GBI Research. This is a licensed product and is not to be photocopied
                                           3.20.4 Reasons for Failure ................................................................................................. 67
                                    4   Conclusion ................................................................................................................................. 68
                                    5   Top R&D Drug Failures - Appendix ........................................................................................... 69
                                        5.1    Market Definitions ........................................................................................................... 69
                                        5.2    Abbreviations .................................................................................................................. 69
                                        5.3    Research Methodology ................................................................................................... 70
                                           5.3.1    Coverage ................................................................................................................. 70
                                           5.3.2    Secondary Research ............................................................................................... 71
                                           5.3.3    Primary Research .................................................................................................... 71
                                           5.3.4    Expert Panel Validation ........................................................................................... 71
                                        5.4    Contact Us ...................................................................................................................... 71
                                        5.5    Disclaimer ....................................................................................................................... 72
                                        5.6    Sources ........................................................................................................................... 72




Top R&D Drug Failures - Toxicity and Serious Adverse Events                                                                            GBIHC110MR /Published JUL 2011
in Late Stage Drug Development are the Major Causes of Drug
Failure                                                                                                                                                                      Page 5
                                                                                       © GBI Research. This is a licensed product and is not to be photocopied
                                    1.1       List of Tables
                                    Table 1:  Top R&D Drug Failures, Number of Drugs Discontinued/ Inactive Pipeline Products,
                                              2005–2010 ....................................................................................................................... 8
                                    Table 2: Top R&D Drug Failures, Number of Drugs Discontinued/ Inactive Pipeline Products by
                                              Sponsor Companies, 2005–2010 ..................................................................................... 9
                                    Table 3: Top R&D Drug Failures, NINDS-ADRDA Diagnostic Criteria for Alzheimer's Disease
                                              (AD), 2011 ...................................................................................................................... 14
                                    Table 4: Top R&D Drug Failures, Zibotentan Phase III Outcomes, 2011 ..................................... 17
                                    Table 5: Top R&D Drug Failures, ASA404 Phase II Outcomes, 2011 ......................................... 27
                                    Table 6: Top R&D Drug Failures, Ocrelizumab: Phase III Clinical Trial Program In Rheumatoid
                                              Arthritis, 2011 ................................................................................................................. 38
                                    Table 7: Top R&D Drug Failures, Taspoglutide List of Trials, 2005–2010 ................................... 47
                                    Table 8: Top R&D Drug Failures, Taspoglutide Trial Details, 2005–2010 .................................... 48
                                    Table 9: Top R&D Drug Failures, Treatment Related Toxicities With Avastin In Phase II Trial (%),
                                              2011 .........................................................................................
								
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