The EU paediatric medicine regulation: is it working? candid A - PowerPoint PPT Presentation

The EU paediatric medicine regulation: is it working? candid A view from a paediatric oncology network λ Bruce Morland Birmingham Children’s Hospital & Innovative Therapies for Children with Cancer

The EU Pediatric Medicine Regulation: • A EU political decision in December 2000 to improve health of children in Europe Principle : obligation/incentives/rewards • A Regulation launched in January 2007 Paediatric Investigation Plan (PIP) Waiver Deferral • A Paediatric Committee working at EMA since July 2007

The EU Pediatric Medicine Regulation: • A EU political decision in December 2000 to improve health of children in Europe Principle : obligation/incentives/rewards • A Regulation launched in January 2007 Paediatric Investigation Plan (PIP) Waiver Deferral • A Paediatric Committee working at EMA since July 2007

Drug Disease MA itcc adenoTK High Grade Gliomas N L-asparaginase ALL N 24 drugs with an Docetaxel NPC Y Bevacizumab RMS Y X approved PIP in oncology Aprepitant vomiting Y Ipilimumab solid tumors N (as of 12/2010) Vandetanib Thyroid N (13 already marketed in adults) Everolimus Sub Ep Astro Y 5 cytotoxic agents Casopitant vomiting Y Plerixafor HSC mobilisation Y X 3 anti-emetic agents Sunitinib GIST Y X Nilotinib CML Y X 13 targeted agents 6-mercaptopurine ALL Y 2 other compounds IGF1R MoAb Ewing tumors N X Rituximab NHL Y X 1 gene therapy product Linifamib solid tumors N Fosaprepitant vomiting Y NOT all PIPs will be completed Denosumab bone metastatsis Y Dasatinib CML, Ph+ALL Y X Bosutinib CML N 19 Waivers L-asparaginase ALL N Deforolimus solid tumours N Cediranib HGG N Data from EMA website Decitabine AML N

PIPs of oncology drugs (as of 12/2010) Drug 2 0 0 8 2 0 0 9 2 0 1 0 2 0 1 1 2 0 1 2 2 0 1 3 2 0 1 4 2 0 1 5 2 0 1 6 2 0 1 7 2 0 1 8 2 0 1 9 adenoTK L-asparaginase Docetaxel Bevacizumab Aprepitant Ipilimumab Vandetanib Everolimus Casopitant Plerixafor Sunitinib Nilotinib 6-mercaptopurine IGF1R MoAb Rituximab Linifanib Fosaprepitant Denosumab Dasatinib Bosutinib L-asparaginase Deforolimus Cediranib NOT all PIPs are ongoing Data from EMA website

Drug Disease MA itcc adenoTK High Grade Gliomas N •6 drugs (25%) in very/extremely L-asparaginase ALL N rare pediatric malignancies: Docetaxel NPC Y Bevacizumab RMS Y X  Nasopharyngeal carcinoma Aprepitant vomiting Y  Thyroid cancer Ipilimumab solid tumors N  GIST Vandetanib Thyroid N Everolimus Sub Ep Astro Y  CML Casopitant vomiting Y  Sub Ep Astro Plerixafor HSC mobilisation Y X  ALL Ph+ Sunitinib GIST Y X Nilotinib CML Y X 6-mercaptopurine ALL Y • 3 drugs in solid tumors IGF1R MoAb Ewing tumors N X Rituximab NHL Y X •Only one drug Linifamib solid tumors N Fosaprepitant vomiting Y in « true » paediatric malignancy Denosumab bone metastatsis Y Dasatinib CML, Ph+ALL Y X •No drug Bosutinib CML N in neuroblastoma, L-asparaginase ALL N Deforolimus solid tumours N medulloblastoma, BSG etc Cediranib HGG N Data from EMA website 12/2010 Decitabine AML N

Waivers Drug Disease Novartis compound Myelofibrosis/PCV Geldanamycin GIST Arzoxifene Osteoporosis Bortezomib Mantle cell lymphoma Mesothelium chimeric Ab Mesothelioma Anti-Il6 Ab Castleman’s •HSP90 inhibitor Cinacalcet Parathyroid Ca Everolimus Renal/pancreatic/carcinoid •Generic target Forodesine CTCL Ingenol SCC GIST story Lapatinib H+N Lenalidomide MDS •Geldanamycin - « no significant Omacetaxine Ph+ALL benefit over existing treatment » Panobinostat CTCL Patupilone Genital/peritoneal •Nilotinib – « clinical studies not Pemetrexed H+N feasible/rarity » Ralitrexed Mesothelioma •Sunitinib – PIP Sorafenib Thyroid

Waivers Drug Drug Disease Disease Novartis compound Novartis compound Myelofibrosis/PCV Myelofibrosis/PCV Geldanamycin Arzoxifene Osteoporosis GIST Bortezomib Arzoxifene Mantle cell lymphoma Osteoporosis Mesothelium chimeric Ab Bortezomib Mantle cell lymphoma Mesothelioma Anti-Il6 Ab Mesothelium chimeric Ab Castleman’s Mesothelioma Anti-Il6 Ab Cinacalcet Parathyroid Ca Castleman’s Cinacalcet Everolimus Renal/pancreatic/carcinoid Parathyroid Ca Everolimus Forodesine Renal/pancreatic/carcinoid CTCL •Proteosome inhibitor Forodesine Ingenol SCC CTCL Lapatinib Ingenol H+N SCC •Generic target Lenalidomide Lapatinib H+N MDS •Phase I in children in USA Lenalidomide Omacetaxine Ph+ALL MDS •Phase II in HD in children in USA Omacetaxine Panobinostat Ph+ALL CTCL Patupilone Panobinostat Genital/peritoneal CTCL Pemetrexed Patupilone Genital/peritoneal H+N Ralitrexed Pemetrexed Mesothelioma H+N Sorafenib Ralitrexed Thyroid Mesothelioma Sorafenib Thyroid

Waivers Drug Drug Disease Disease Novartis compound Novartis compound Myelofibrosis/PCV Myelofibrosis/PCV Arzoxifene Geldanamycin Osteoporosis GIST Arzoxifene Bortezomib Mantle cell lymphoma Osteoporosis Mesothelium chimeric Ab Bortezomib Mantle cell lymphoma Mesothelioma Mesothelium chimeric Ab Anti-Il6 Ab Mesothelioma Castleman’s Cinacalcet Anti-Il6 Ab Castleman’s Parathyroid Ca Everolimus Cinacalcet Parathyroid Ca Renal/pancreatic/carcinoid Everolimus Forodesine CTCL Renal/pancreatic/carcinoid Forodesine Ingenol CTCL SCC Ingenol Lapatinib SCC H+N Lapatinib Lenalidomide MDS H+N Omacetaxine Lenalidomide Ph+ALL MDS •mTOR inhibitor Omacetaxine Panobinostat Ph+ALL CTCL •Generic target Panobinostat Patupilone CTCL Genital/peritoneal Pemetrexed Patupilone Genital/peritoneal H+N •PIP in tuberose sclerosis/GCA Ralitrexed Pemetrexed Mesothelioma H+N Sorafenib Ralitrexed Thyroid Mesothelioma Sorafenib Thyroid

Waivers Drug Drug Disease Disease Novartis compound Novartis compound Myelofibrosis/PCV Myelofibrosis/PCV Arzoxifene Geldanamycin Osteoporosis GIST Bortezomib Arzoxifene Mantle cell lymphoma Osteoporosis Mesothelium chimeric Ab Bortezomib Mesothelioma Mantle cell lymphoma •« likely to be unsafe » Anti-Il6 Ab Mesothelium chimeric Ab Mesothelioma Castleman’s •Phase I study in children with Cinacalcet Anti-Il6 Ab Castleman’s Parathyroid Ca solid tumours and MDS in the Cinacalcet Everolimus Parathyroid Ca Renal/pancreatic/carcinoid Forodesine Everolimus Renal/pancreatic/carcinoid CTCL USA Forodesine Ingenol SCC CTCL Lapatinib Ingenol H+N SCC Lenalidomide Lapatinib H+N MDS Omacetaxine Lenalidomide Ph+ALL MDS Panobinostat Omacetaxine CTCL Ph+ALL Panobinostat Patupilone Genital/peritoneal CTCL Pemetrexed Patupilone Genital/peritoneal H+N Pemetrexed Ralitrexed Mesothelioma H+N Sorafenib Ralitrexed Thyroid Mesothelioma Sorafenib Thyroid

Waivers Drug Drug Disease Disease Novartis compound Novartis compound Myelofibrosis/PCV Myelofibrosis/PCV Geldanamycin Arzoxifene Osteoporosis GIST Bortezomib Arzoxifene Mantle cell lymphoma Osteoporosis Bortezomib Mesothelium chimeric Ab Mesothelioma Mantle cell lymphoma Anti-Il6 Ab Mesothelium chimeric Ab Castleman’s Mesothelioma Cinacalcet Anti-Il6 Ab Parathyroid Ca Castleman’s •Antifolate (methotrexate) Everolimus Cinacalcet Parathyroid Ca Renal/pancreatic/carcinoid •Generic antimetabolite Everolimus Forodesine Renal/pancreatic/carcinoid CTCL Ingenol Forodesine CTCL SCC •Phase I&II study of pemetrexed Ingenol Lapatinib H+N SCC in solid tumours in USA Lenalidomide Lapatinib MDS H+N Lenalidomide Omacetaxine Ph+ALL MDS Panobinostat Omacetaxine CTCL Ph+ALL Patupilone Panobinostat CTCL Genital/peritoneal Patupilone Pemetrexed Genital/peritoneal H+N Ralitrexed Pemetrexed Mesothelioma H+N Sorafenib Ralitrexed Thyroid Mesothelioma Sorafenib Thyroid

Waivers Drug Drug Disease Disease Novartis compound Novartis compound Myelofibrosis/PCV Myelofibrosis/PCV Arzoxifene Geldanamycin GIST Osteoporosis Arzoxifene Bortezomib Osteoporosis Mantle cell lymphoma Mesothelium chimeric Ab Bortezomib Mesothelioma Mantle cell lymphoma Anti-Il6 Ab Mesothelium chimeric Ab Mesothelioma Castleman’s •Raf/VEGF/PDGFR Cinacalcet Anti-Il6 Ab Castleman’s Parathyroid Ca Cinacalcet Everolimus Parathyroid Ca Renal/pancreatic/carcinoid •Generic targets Everolimus Forodesine CTCL Renal/pancreatic/carcinoid •Phase I&II studies in solid Forodesine Ingenol CTCL SCC tumours and ALL in USA Lapatinib Ingenol SCC H+N Lapatinib Lenalidomide H+N MDS •In regular use in young patients Omacetaxine Lenalidomide MDS Ph+ALL with hepatocellular Ca Panobinostat Omacetaxine CTCL Ph+ALL Panobinostat Patupilone CTCL Genital/peritoneal Patupilone Pemetrexed H+N Genital/peritoneal Ralitrexed Pemetrexed Mesothelioma H+N Sorafenib Ralitrexed Thyroid Mesothelioma Sorafenib Thyroid