Risk Evaluation and Mitigation Strategy (REMS) - Opioids, Erythropoesis-Stimulating Agents and Cancer Therapeutics are the Most Important Classes That Require REMS by GBIResearch

VIEWS: 95 PAGES: 88

More Info
									    Risk Evaluation and Mitigation Strategy (REMS) - Opioids,
   Erythropoesis-Stimulating Agents and Cancer Therapeutics
       are the Most Important Classes That Require REMS
 Reference Code: GBIHC087MR                                                                                            Publication Date: May 2011


                                       Risk Evaluation and Mitigation Strategies (REMS) to Ensure Safe Use of Opioids
Risk Evaluation and                    Importance and efficacy of opioids in pain management is well known and acknowledged by
Mitigation Strategies                  organizations such as the American Pain Society (APS), American Academy of Pain Medicine
(REMS) are required by                 (AAPM) and World Health Organization (WHO). However, nonmedical use including misuse,
the FDA to ensure that the             abuse, addiction and overdose are some of the significant risks associated with opioids. Opioid
benefits of a drug                     prescription drug abuse has shown an alarming increase over the last few years. Number of
outweigh its risks. One in             hydrocodone and oxycodone prescriptions increased from approximately 141 million in 2004 to 179
three small molecules                  million in 2009.
approved since 2008 have
required REMS. Important               In an effort to minimize these risks, opioids are made available through REMS. REMS ensure that
drug classes that have                 opioids‘ benefits outweigh its safety risks and that healthcare professionals are aware will allow
required REMS include                  appropriate patients continued access to opioids. A class wide REMS for long-acting opioids has
Long-acting opioids and                been suggested by the FDA but the design remains to be specified.
Eryhtropoesis-stimulating
                                        Risk Evaluation and Mitigation Strategies, Opioids, 2011
agents.

                                                                  Long-acting Opioids – Oxycodone, Embeda, Exalgo

                        Fig 1 and 22

                                                   Indications        Moderate-to-severe pain in cancer, neuropathic and arthritis
                                                                      patients


                                                      Safety Issues          Risk of overdose, abuse, addiction and serious complications
                                                                             due to medication errors


                                                               REMS              Class-wide REMS is required for long acting opioids but
                                                              Program            the design has not yet been specified


                                                                   REMS              Medication Guide, Elements to assure safe use,
                                                                  Elements           Implementation system, Communication plan



                                                                 Manufacturer




                                        Source: GBI Research, Drug Abuse Warning Network




Risk Evaluation and Mitigation Strategy (REMS) - Opioids,                                                         GBIHC087MR / Published MAY 2011
Erythropoesis-Stimulating Agents and Cancer Therapeutics are
the Most Important Classes That Require REMS                                                                                                    Page 1
                                                                                © GBI Research. This is a licensed product and is not to be photocopied
                                     REMS Elements such as ETASU have seen increased implementation in the recent past
                                     Since the introduction of the Food and Drug Administration Amendments Act (FDAAA), the FDA
                                     approved 23 REMS in 2008, 72 REMS in 2009 and 63 REMS in 2010.

                                      Risk Evaluation and Mitigation Strategies, Requirement of additional REMS component,
                                      2008-2010

                                                                       80


                                                                       70


                                            Number of REMS Approvals   60                              22



                                                                       50                                                           28


                                                                       40


                                                                       30
                                                                                                       50
                                                                       20    6
                                                                                                                                    35

                                                                       10
                                                                            17


                                                                        0
                                                                            2008                      2009                         2010

                                                                                   Medication Guide   Additional REMS Component


                                      Source: GBI Research, US FDA, ParagonRx REMS Hub, REMSadvisor.com




                                     Approximately 65% of all the approved REMS (since 2008) required a medication guide. However,
                                     medication guide-only REMS have decreased and components such as ETASUs and
                                     implementation systems have become key elements of REMS. ETASUs may be required if the
                                     drug is associated with serious adverse events and the medication guide/
                                     In an interview with GBI Research (April 2011), David Kirk, Commercial Development Director for
                                     ParagonRx, said ―One of three small molecules approved since 2008 have required REMS.
                                     MedGuide-only REMS have decreased as a percentage of total REMS approved in each year.‖




Risk Evaluation and Mitigation Strategy (REMS) - Opioids,                                                               GBIHC087MR / Published MAY 2011
Erythropoesis-Stimulating Agents and Cancer Therapeutics are
the Most Important Classes That Require REMS                                                                                                       Page 2
                                                                                   © GBI Research. This is a licensed product and is not to be photocopied
                                        FDA mandates REMS for Erythropoiesis-Stimulating Agents (ESAs)
                                        ESAs are indicated for the treatment of anemia resulting from chronic kidney failure, chemotherapy,
                                        Human Immunodeficiency Virus (HIV) infection, and are also used to reduce the number of blood
                                        transfusions during and after certain major surgeries. ESAs are associated with an increase in risk
                                        of tumor growth and reduction in survival rate in patients with cancer who use ESAs. Studies have
                                        also shown that ESAs can increase the risk of heart attack, heart failure, stroke, or blood clots in
                                        patients who use these drugs for other conditions.
                                        ESAs included in the REMS program are Amgen‘s Epogen (epoetin alfa), Procrit (epoetin alfa), and
                                        Aranesp (darbepoetin alfa).The ESA APPRISE (Assisting Providers and Cancer Patients with Risk
                                        Information for the Safe use of ESAs) Oncology program, launched on March 24, 2010, was
                                        developed by Amgen in collaboration with Centocor Ortho Biotech Products for healthcare
                                        professionals who prescribe ESAs to patients with cancer. All ESAs are required to be prescribed
                                        with REMS to ensure their safe use.

                                         Risk Evaluation and Mitigation Strategies, Erythropoiesis-Stimulating Agents, 2011


                                                            Erythropoiesis-Stimulating Agents – Epogen, Procrit and Aranesp

                         Fig 3 and 24

                                                     Indications        Anemia in Chronic Renal Failure, HIV and Cancer patients



                                                        Safety Issues          Increase in risk of tumor growth; Shorten survival in cancer
                                                                               patients

                                                                                    APPRISE (Assisting Providers and Cancer Patients with
                                                                 REMS
                                                                                    Risk Information for the Safe use of ESAs) Oncology
                                                                Program
                                                                                    program

                                                                     REMS               Medication Guide, Communication plan, Elements to
                                                                    Elements            assure safe use, Implementation system



                                                                   Manufacturer


                                         Source: GBI Research, Amgen press releases, REMSadvisor.com




Risk Evaluation and Mitigation Strategy (REMS) - Opioids,                                                            GBIHC087MR / Published MAY 2011
Erythropoesis-Stimulating Agents and Cancer Therapeutics are
the Most Important Classes That Require REMS                                                                                                      Page 3
                                                                                  © GBI Research. This is a licensed product and is not to be photocopied
                                     1         Table of Contents
                                     1   Table of Contents ........................................................................................................................ 4
                                         1.1    List of Tables..................................................................................................................... 7
                                         1.2    List of Figures ................................................................................................................... 8
                                     2   Risk Evaluation and Mitigation Strategies - Introduction.............................................................. 9
                                         2.1    GBI Research Report Guidance ..................................................................................... 10
                                     3   Risk Evaluation and Mitigation Strategies - Drug Development and Pharmacovigilance .......... 11
                                         3.1    Drug Discovery and Development .................................................................................. 11
                                            3.1.1    Early Stage Drug Discovery..................................................................................... 11
                                            3.1.2    Phase I .................................................................................................................... 12
                                            3.1.3    Phase II ................................................................................................................... 12
                                            3.1.4    Phase III .................................................................................................................. 12
                                            3.1.5    Registration ............................................................................................................. 12
                                            3.1.6    Phase IV .................................................................................................................. 13
                                         3.2    Pharmacovigilance.......................................................................................................... 14
                                            3.2.1    Pharmacovigilance in Different Countries ................................................................ 14
                                            3.2.2    Pharmacovigilance in Europe .................................................................................. 14
                                            3.2.3    Pharmacovigilance in the US................................................................................... 15
                                         3.3    Post Marketing Research and Surveillance .................................................................... 15
                                            3.3.1    Post marketing Surveillance .................................................................................... 16
                                            3.3.2    Adverse Event Reporting System (AERS) ............................................................... 17
                                            3.3.3    Center for Drug Evaluation and Research (CDER) ................................................. 17
                                         3.4    Need for REMS ............................................................................................................... 18
                                            3.4.1    Number of Adverse Events Reports ........................................................................ 18
                                            3.4.2    Increase in healthcare costs in top seven geographies ........................................... 19
                                     4   Risk Evaluation and Mitigation Strategies - Overview ............................................................... 20
                                         4.1    What are REMS? ............................................................................................................ 20
                                            4.1.1    RiskMAPs and REMS .............................................................................................. 20
                                            4.1.2    Components of REMS ............................................................................................. 21
                                         4.2    Food and Drug Administration Amendments Act (FDAAA) of 2007 ................................ 22
                                            4.2.1    Prescription Drug User Fee Amendments, 2007 ..................................................... 22
                                            4.2.2    Medical Device User Fee Amendments, 2007......................................................... 22
                                            4.2.3    Pediatric Research Equity Act, 2007 ....................................................................... 22
                                            4.2.4    Best Pharmaceuticals for Children Act, 2007 .......................................................... 22
                                         4.3    Approved Risk Evaluation and Mitigation Strategies - 2008-2010 .................................. 23
                                            4.3.1    FDA Approved REMS, 2008 .................................................................................... 27
                                            4.3.2    FDA Approved REMS, 2009 .................................................................................... 29
                                            4.3.3    FDA Approved REMS, 2010 .................................................................................... 33
                                         4.4    Deemed REMS Approvals .............................................................................................. 37
                                         4.5    Implications of REMS ...................................................................................................... 38
                                         4.6    REMS by Drug Class ...................................................................................................... 39
                                         4.7    REMS and Generics ....................................................................................................... 40
                                     5   Risk Evaluation and Mitigation Strategies - Opioids .................................................................. 41
                                         5.1    Introduction ..................................................................................................................... 41
                                         5.2    Opioids and REMS ......................................................................................................... 41
                                         5.3    Case Studies - Opioids ................................................................................................... 44
                                            5.3.1    Oxycodone .............................................................................................................. 45
                                            5.3.2    Embeda ................................................................................................................... 46
                                            5.3.3    Exalgo ..................................................................................................................... 46
                                            5.3.4    Onsolis .................................................................................................................... 47
                                     6   Risk Evaluation and Mitigation Strategies - Erythropoiesis-Stimualting Agents ........................ 50
                                         6.1    Erythropoiesis-Stimulating Agents (ESAs) ...................................................................... 50
                                         6.2    ESA Drug Profiles ........................................................................................................... 51
                                            6.2.1    Epogen .................................................................................................................... 51


Risk Evaluation and Mitigation Strategy (REMS) - Opioids,                                                                           GBIHC087MR / Published MAY 2011
Erythropoesis-Stimulating Agents and Cancer Therapeutics are
the Most Important Classes That Require REMS                                                                                                                               Page 4
                                                                                       © GBI Research. This is a licensed product and is not to be photocopied
                                           6.2.2    Aranesp ................................................................................................................... 53
                                           6.2.3    Procrit/Eprex ............................................................................................................ 55
                                        6.3    Risk Evaluation and Mitigation Strategies – Other Case Studies .................................... 58
                                           6.3.1    Accutane (Isotretinoin) – iPLEDGE Program ........................................................... 58
                                           6.3.2    Tysabri (Natalizumab) – TOUCH Program .............................................................. 59
                                           6.3.3    Nplate (romiplostim) – NEXUS Program ................................................................. 60
                                     7 Risk Evaluation and Mitigation Strategies – Opportunities in Niche Markets ............................. 61
                                        7.1    REMS and Personalized Medicine.................................................................................. 61
                                        7.2    REMS and Orphan Drugs ............................................................................................... 62
                                     8 Risk Evaluation and Mitigation Strategies - Electronic Record Maintenance and IT Solutions . 64
                                        8.1    Electronic Data Capture (EDC) ....................................................................................... 64
                                           8.1.1    Cost Saving Scenario in EDC .................................................................................. 65
                                           8.1.2    Case Studies ........................................................................................................... 66
                                        8.2    Electronic Patient Report Outcome System (ePRO) ....................................................... 67
                                           8.2.1    Cost Saving Scenario with eDiaries......................................................................... 69
                                        8.3    Interactive Voice Response Systems (IVRS) .................................................................. 70
                                        8.4    Clinical Data Management Systems (CDMS) ................................................................. 71
                                        8.5    Information Technology in the Manufacturing & Supply Chain........................................ 72
                                           8.5.1    E-Pedigree Solutions ............................................................................................... 72
                                           8.5.2    Track and Trace Solutions ....................................................................................... 73
                                           8.5.3    Product Callback Management................................................................................ 74
                                           8.5.4    Sample Distribution Management............................................................................ 74
                                     9 Risk Evaluation and Mitigation Strategies – Competitive Landscape ........................................ 75
                                        9.1    Inflexxion, Inc .................................................................................................................. 75
                                           9.1.1    Business Description ............................................................................................... 75
                                           9.1.2    Snapshot ................................................................................................................. 75
                                        9.2    inVentiv Health ................................................................................................................ 76
                                           9.2.1    Business Description ............................................................................................... 76
                                           9.2.2    ParagonRx............................................................................................................... 76
                                           9.2.3    Snapshot ................................................................................................................. 77
                                        9.3    BioTrak Research ........................................................................................................... 78
                                           9.3.1    Business Description ............................................................................................... 78
                                           9.3.2    Snapshot ................................................................................................................. 78
                                           9.3.3    REMS Solutions - Case Study ................................................................................. 79
                                     10 Other Major Clinical Research Organizations offering REMS services ..................................... 80
                                        10.1 PRA International ............................................................................................................ 80
                                           10.1.1 Business Description ............................................................................................... 80
                                           10.1.2 Services Offered ...................................................................................................... 80
                                        10.2 Covance .......................................................................................................................... 81
                                           10.2.1 Business Description ............................................................................................... 81
                                           10.2.2 Services Offered ...................................................................................................... 81
                                        10.3 Kendle International Inc. ................................................................................................. 82
                                           10.3.1 Business Overview .................................................................................................. 82
                                           10.3.2 Services Offered ...................................................................................................... 82
                                        10.4 Pharmaceutical Product Development ............................................................................ 82
                                           10.4.1 Business Description ............................................................................................... 82
                                           10.4.2 Services Offered ...................................................................................................... 82
                                     11 Risk Evaluation and Mitigation Strategies - The Future ............................................................. 84
                                     12 Appendix ................................................................................................................................... 85
                                        12.1 Market Definitions ........................................................................................................... 85
                                        12.2 Abbreviations .................................................................................................................. 85
                                        12.3 Research Methodology ................................................................................................... 86
                                           12.3.1 Coverage ................................................................................................................. 86
                                           12.3.2 Secondary Research ............................................................................................... 87
                                           12.3.3 Primary Research .................................................................................................... 87

Risk Evaluation and Mitigation Strategy (REMS) - Opioids,                                                                            GBIHC087MR / Published MAY 2011
Erythropoesis-Stimulating Agents and Cancer Therapeutics are
the Most Important Classes That Require REMS                                                                                                                                 Page 5
                                                                                        © GBI Research. This is a licensed product and is not to be photocopied
                                        12.4    Expert Panel Validation ................................................................................................... 87
                                        12.5    Contact Us ...................................................................................................................... 88
                                        12.6    Sources ........................................................................................................................... 88
                                        12.7    Disclaimer ....................................................................................................................... 88




Risk Evaluation and Mitigation Strategy (REMS) - Opioids,                                                                          GBIHC087MR / Published MAY 2011
Erythropoesis-Stimulating Agents and Cancer Therapeutics are
the Most Important Classes That Require REMS                                                                                                                                Page 6
                                                                                     © GBI Research. This is a licensed product and is not to be photocopied
                                     1.1     List of Tables
                                     Table 1:    Risk Evaluation and Mitigation Strategies, List of FDA Approved REMS, 2008 ............. 27
                                     Table 2:    Risk Evaluation and Mitigation Strategies, List of FDA Approved REMS, 2009 ............. 29
                                     Table 3:    Risk Evaluation and Mitigation Strategies, List of FDA Approved REMS, 2010 ............. 33
                                     Table 4:    Risk Evaluation and Mitigation Strategies, Deemed REMS, 2010 ................................. 37




Risk Evaluation and Mitigation Strategy (REMS) - Opioids,                                                    GBIHC087MR / Published MAY 2011
Erythropoesis-Stimulating Agents and Cancer Therapeutics are
the Most Important Classes That Require REMS                                                                                               Page 7
                                                                           © GBI Research. This is a licensed product and is not to be photocopied
                                     1.2       List of Figures
                                     Figure 1:  Risk Evaluation and Mitigation Strategies, Stages of Drug Development, 2011 ............ 13
                                     Figure 2:  Risk Evaluation and Mitigation Strategies, Post Marketing Surveillance System , 2011 16
                                     Figure 3:  Risk Evaluation and Mitigation Strategies, System of safety data gathering, 2011 ........ 16
                                     Figure 4:  Risk Evaluation and Mitigation Strategies, Number of Adverse Events in the US, 2000-
                                                2011 ............................................................................................................................... 18
                                     Figure 5: Risk Evaluation and Mitigation Strategies, Healthcare Expenditure 1998-2008 ............. 19
                                     Figure 6: Risk Evaluation and Mitigation Strategies, Components of REMS ................................ 21
                                     Figure 7: Risk Evaluation and Mitigation Strategies, REMS Approvals (2008-2010) .................... 23
                                     Figure 8: Risk Evaluation and Mitigation Strategies, Components of REMS, 2008-2010 ............. 24
                                     Figure 9: Risk Evaluation and Mitigation Strategies, Requirement of additional REMS component,
                                                2008-2010 ...................................................................................................................... 25
                                     Figure 10: Risk Evaluation and Mitigation Strategies, Safety Issues, 2008-2010............................ 25
                                     Figure 11: Risk Evaluation and Mitigation Strategies, Components of REMS, 2008 ....................... 28
                                     Figure 12: Risk Evaluation and Mitigation Strategies, Components of REMS, 2009 ....................... 32
                                     Figure 13: Risk Evaluation and Mitigation Strategies, Components of REMS, 2010....................... 36
                                     Figure 14: Risk Evaluation and Mitigation Strategies, Implications for Stakeholders ...................... 38
                                     Figure 15: Risk Evaluation and Mitigation Strategies, Important Drug Classes Requiring REMS ... 39
                                     Figure 16: Risk Evaluation and Mitigation Strategies, Number of ED Visits Due To Drug Abuse in
                                                the US, 2004 and 2008 .................................................................................................. 42
                                     Figure 17: Risk Evaluation and Mitigation Strategies, Number of Opioid drug prescriptions (in
                                                million), 1991-2009......................................................................................................... 43
                                     Figure 18: Risk Evaluation and Mitigation Strategies, Number of Emergency Department Visits in
                                                the US, 2004-2008 ......................................................................................................... 43
                                     Figure 19: Risk Evaluation and Mitigation Strategies, Opioids, 2011 .............................................. 44
                                     Figure 20: Risk Evaluation and Mitigation Strategies, Onsolis, 2011 .............................................. 49
                                     Figure 21: Risk Evaluation and Mitigation Strategies, Erythropoiesis-Stimulating Agents, 2011..... 50
                                     Figure 22: Risk Evaluation and Mitigation Strategies, Accutane Case Study, 2011 ........................ 58
                                     Figure 23: Risk Evaluation and Mitigation Strategies, Tysabri Case Study, 2011 ........................... 59
                                     Figure 24: Risk Evaluation and Mitigation Strategies, Nplate, Case Study, 2011 ........................... 60
                                     Figure 25: Risk Evaluation and Mitigation Strategies, Electronic Data Capture through e-CRF, 2009
                                                ....................................................................................................................................... 64
                                     Figure 26: Risk Evaluation and Mitigation Strategies, EDC System- Cost Saving Scenario, 2009 . 65
                                     Figure 27:Risk Evaluation and Mitigation Strategies, EDC Cost Saving in Clinical Trials – By
                                                Therapy , 2009 ............................................................................................................... 66
                                     Figure 28: Risk Evaluation and Mitigation Strategies, Cost Saving Scenario of ePRO Solutions,
                                                2009 ............................................................................................................................... 68
                                     Figure 29: Risk Evaluation and Mitigation Strategies, Case Study of ePRO Solutions, 2009 ......... 69
                                     Figure 30: Risk Evaluation and Mitigation Strategies, Integration of IVR with other Systems, 2009 70
                                     Figure 31: Risk Evaluation and Mitigation Strategies, Clinical Data Management Flow, 2009 ........ 71
                                     Fig
								
To top