data page
Drug pipeline: 2Q14 Laura DeFrancesco FDA drug approvals are on track with last year’s tally by 2Q13. Apart from MannKind’s inhaled insulin, Merck’s PAR-1 antagonist with its potential safety benefit and long-acting versions of GLP-1 and Factor VIII were approved. A slew of hepatitis C drugs in various combinations is movHistoric US regulatory approvals by lead indication area Infectious disease (108) Oncology (109) Autoimmune/immunology (48) Neurology (48) Cardiovascular (49) Endocrine (36) Hematology (25) Metabolic (27) Ophthalmology (20) Psychiatry (15) Gastroenterology (20) Respiratory (19) Obstetrics/gynecology (12) Dermatology (8) Rheumatology (4) Other (98)
Number of FDA approvals
60 50 40 30 20
npg
0
19 9 19 5 9 19 6 9 19 7 9 19 8 9 20 9 0 20 0 0 20 1 0 20 2 0 20 3 0 20 4 0 20 5 06 20 0 20 7 0 20 8 0 20 9 1 20 0 1 20 1 1 20 2 1 20 3 14 *
© 2014 Nature America, Inc. All rights reserved.
10
Year
*2014 partial year from Jan. 1 to June 30. Numbers in parentheses after indication areas in legend are total approvals since 1995. Source: US Food and Drug Administration; BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Notable clinical trial results (2Q14) Drug/company Cvac/Prima BioMed
Indication Ovarian cancer
Summary 6/18/2014. Four out of 28 patients responded in a phase 2 study of autologous dendritic vaccine against mucin 1. J. Immunother. Cancer 2, 16 (2014) Melanoma 4/16/2014. Six of 8 patients responded in a phase 1/2 CDX-1401/ of human monoclonal antibody for dendritic antigen 205 Celldex fused to tumor antigen NY-ESO1. Sci.Transl. Med. 6, Therapeutics 232ra51 (2014) DiaPep277/ Diabetes 4/30/2014. 23% of patients in phase 3 trial responded to Hyperion mellitus, type I a 22-amino-acid synthetic peptide derived from heat shock protein 60. Diabetes Care 37, 1392–1414 (2014) Letermovir/ Cytomegalovirus 5/8/2014. Quinazoline inhibitor of CMV terminase reduced Merck (CMV) incidence of HCV in patients after allogeneic transplant. N. Engl. J. Med. 370, 1781–1789 (2014) Idiopathic pul- 5/18/2014. Patients receiving p38 kinase inhibitor in a Esbriet (pirmonary fibrosis phase 3 trial showed ~50% amelioration of lung function fenidone)/ decline. N. Engl. J. Med. 370, 2083–2092 (2014) InterMune Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
ing toward registration. New breakthrough drug designations include the first chimeric antigen receptor (CAR) T-cell therapy and gene therapy to receive the designation. This new category for drug review seems to be in favor both at the FDA and in companies. Notable upcoming regulatory decisions (3Q14) (continued) Drug/company Balugrastim/Teva
Indication Neutropenia/ leukopenia
Summary 9/30/2014. EMA decision for Neulasta biosimilar (albumin fused to G-CSF)
FDA, US Food and Drug Administration; PDUFA, Prescription Drug User Fee Act; EMA, European Medicines Agency; HPV, human papillomavirus. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Notable regulatory approvals (2Q14) Drug/company
Indication
Product registration Tanzeum (albiglutide)/GSK Zontivity (vorapaxar)/ Merck Eloctate (Factor VIII)/ Biogen Idec Sivextro (tedisolid phosphate)/Cubist Afrezza (insulin)/ MannKind
Diabetes mellitus, 4/15/2014. FDA approved long-acting GLP type 2 albumin fusion Cardiovascular disease 5/8/2014. FDA approved protease-activated receptor 1 antagonist Hemophilia A 6/6/2014. FDA approved long-acting Factor VIII–Fc fusion Skin and skin-structure 6/20/2014. FDA approved oxazolidinone antibacterial infections biotic for drug-resistant Gram-positive bacteria Diabetes mellitus, 6/27/2014. FDA approved this inhaled insulin type II
Breakthrough drug designation Bexsero/Novartis Meningitis B Mydicar/Celledon
Heart failure
Nivolumab/BMS
Hodgkin lymphoma
Elotuzumab/BMS
Multiple myeloma
CD-1686/Clovis Oncology
Second-line EGFR T790M mutationpositive NSCLC Urothelial bladder cancer Mycobacterial lung disease Antidote for Pradaxa
MMDPL3280A/ Genentech Arikayce/Insmed
Idarucizumab/ Boehringer Ingleheim Blinatumomab/ Acute lymphoblastic Amgen leukemia CTL019/Novartis Relapsed refractory acute lymphoblastic leukemia
Drug information
4/7/2014. Quadrivalent vaccine against meningitis B 4/10/2014. AAV1 gene therapy to replace deficiency in enzyme Serca2A 5/14/2014. Anti-PD-1 monoclonal antibody 5/19/2014. Humanized IgG1 against signaling lymphocyte activation molecule 5/19/2014. Covalent inhibitor of T790M mutant EGFR 5/31/2014. Anti-PDL1 human IgG1 monoclonal antibody with engineered Fc domain 6/19/2014. Inhaled liposomal amikacin 6/25/2014. Humanized Fab fragment targeting Pradaxa 7/1/2014. Bi-specific (CD19/CD3) T-cell engager (BiTE) 7/7/2014. Personalized chimeric antigen receptor T-cell therapy
Notable upcoming regulatory decisions (3Q14)
FDA, US Food and Drug Administration; NSCLC, non–small cell lung cancer. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Drug/company Cobicistat/Gilead
Indication HIV/AIDS
Notable regulatory setbacks (2Q14)
Elvitegravir/Gilead
HIV/AIDS
Lynparza (olaparib)/AstraZeneca Dulaglutide/Eli Lilly Triumeq/GSK
Ovarian cancer
Faridak (panobinostat lactate)/ Novartis Daclatasvir/BMS
Diabetes mellitus, type II HIV/AIDS Multiple myeloma
9/26/2014. US FDA PDUFA for GLP-1–IgG4 Fc fusion 10/22/2014. US FDA PDUFA for HIV integrase inhibitor 11/2/2014. US FDA PDUFA for HDAC inhibitor
12/5/2014. US FDA PDUFA inhibitor of hepatitis C NS5A ABT-450,267,333/ Hepatitis C 12/19/2014. US FDA PDUFA for hepatitis C NS3 AbbVie protease/NS5A protein inhibitor combination Otezla (apremilast)/ Psoriasis 9/23/2014. US FDA PDUFA for phosphodiesterase 4 Celgene inhibitor OBI-1/Baxter Acquired hemo10/10/2014. US FDA PDUFA for recombinant porphilia cine B domain depleted factor VIII HyQvia/Baxter Primary immuno- 9/2/2014. US FDA PDUFA for subcutaneous human deficiencies IgG with recombinant human hyaluronidase Natpara/NPS Hypoparathyroidism 10/24/2014. US FDA PDUFA for recombinant parathyoid hormone Pembrolizumab/ Melanoma 10/28/2014. US FDA PDUFA for humanized IgG4 Merck monoclonal antibody against PD-1 V-503/Merck Human papillo11/1/2014. US FDA PDUFA for this 9-valent mavirus vaccine against HPV Chondrosphere/ Cartilage repair 9/1/2014. EMA decision for in vitro cultured autoloco.don gous cartilage
710
Hepatitis C
Summary 10/3/2014. US FDA PDUFA for cytochrome P450 3A pharmacokinetics enhancer 10/4/2014. US FDA PDUFA for HIV integrase inhibitor 10/3/2014. US FDA PDUFA for PARP inhibitor
Drug/company Indication Vintafolide/ Ovarian Endocyte cancer PEGPH20/ Halozyme
Pancreatic cancer
MetMab (onartuzumab)/ Roche Ipafricept/ OncoMed
Gastric, colorectal, liver cancer
Liver, ovarian, pancreatic cancer Nimotuzumab/ Non–small CIMAB cell lung cancer MAGE-A3/ Non–small GSK cell lung cancer ALD-401/ Ischemic Cytomedix stroke Davunetide/ Endo
Drug information 5/19/2014. Application for market authority withdrawn when the folate-conjugated vinca alkaloid failed to meet progression-free survival endpoint 4/9/2014. Company halted phase 2 trial of pegylated human recombinant hyaluronidase due to excess thrombosis in experimental arm 4/17/2014. Company put advanced clinical trials on hold due to lack of efficacy of anti-Met monoclonal antibody 6/19/2014. Company halted phase 1 trial of small-molecule Wnt inhibitor after bone adverse effects 4/25/2014. Company halted enrollment in phase 3 trial of antiEGFR monoclonal antibody after four patient deaths
4/2/2014. Phase 3 trial halted due to inability to identify patients benefitting from liposomal recombinant MAGE-3 complexed lipid and CpG oligonucleotide 5/6/2014. Program discontinued when stroke patients receiving bone marrow–derived stem cells showed no improvement in phase 2 trial Progressive 5/27/2014. Patients in phase 3 trial showed no improvement with intranasal 8 amino acid peptide fragment of activity-depensupranuclear palsy dent neuroprotective protein
Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Laura DeFrancesco is Senior Editor at Nature Biotechnology.
volume 32 NUMBER 8 AUGUST 2014 nature biotechnology
Drug pipeline: 2Q14 Laura DeFrancesco FDA drug approvals are on track with last year’s tally by 2Q13. Apart from MannKind’s inhaled insulin, Merck’s PAR-1 antagonist with its potential safety benefit and long-acting versions of GLP-1 and Factor VIII were approved. A slew of hepatitis C drugs in various combinations is movHistoric US regulatory approvals by lead indication area Infectious disease (108) Oncology (109) Autoimmune/immunology (48) Neurology (48) Cardiovascular (49) Endocrine (36) Hematology (25) Metabolic (27) Ophthalmology (20) Psychiatry (15) Gastroenterology (20) Respiratory (19) Obstetrics/gynecology (12) Dermatology (8) Rheumatology (4) Other (98)
Number of FDA approvals
60 50 40 30 20
npg
0
19 9 19 5 9 19 6 9 19 7 9 19 8 9 20 9 0 20 0 0 20 1 0 20 2 0 20 3 0 20 4 0 20 5 06 20 0 20 7 0 20 8 0 20 9 1 20 0 1 20 1 1 20 2 1 20 3 14 *
© 2014 Nature America, Inc. All rights reserved.
10
Year
*2014 partial year from Jan. 1 to June 30. Numbers in parentheses after indication areas in legend are total approvals since 1995. Source: US Food and Drug Administration; BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Notable clinical trial results (2Q14) Drug/company Cvac/Prima BioMed
Indication Ovarian cancer
Summary 6/18/2014. Four out of 28 patients responded in a phase 2 study of autologous dendritic vaccine against mucin 1. J. Immunother. Cancer 2, 16 (2014) Melanoma 4/16/2014. Six of 8 patients responded in a phase 1/2 CDX-1401/ of human monoclonal antibody for dendritic antigen 205 Celldex fused to tumor antigen NY-ESO1. Sci.Transl. Med. 6, Therapeutics 232ra51 (2014) DiaPep277/ Diabetes 4/30/2014. 23% of patients in phase 3 trial responded to Hyperion mellitus, type I a 22-amino-acid synthetic peptide derived from heat shock protein 60. Diabetes Care 37, 1392–1414 (2014) Letermovir/ Cytomegalovirus 5/8/2014. Quinazoline inhibitor of CMV terminase reduced Merck (CMV) incidence of HCV in patients after allogeneic transplant. N. Engl. J. Med. 370, 1781–1789 (2014) Idiopathic pul- 5/18/2014. Patients receiving p38 kinase inhibitor in a Esbriet (pirmonary fibrosis phase 3 trial showed ~50% amelioration of lung function fenidone)/ decline. N. Engl. J. Med. 370, 2083–2092 (2014) InterMune Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
ing toward registration. New breakthrough drug designations include the first chimeric antigen receptor (CAR) T-cell therapy and gene therapy to receive the designation. This new category for drug review seems to be in favor both at the FDA and in companies. Notable upcoming regulatory decisions (3Q14) (continued) Drug/company Balugrastim/Teva
Indication Neutropenia/ leukopenia
Summary 9/30/2014. EMA decision for Neulasta biosimilar (albumin fused to G-CSF)
FDA, US Food and Drug Administration; PDUFA, Prescription Drug User Fee Act; EMA, European Medicines Agency; HPV, human papillomavirus. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Notable regulatory approvals (2Q14) Drug/company
Indication
Product registration Tanzeum (albiglutide)/GSK Zontivity (vorapaxar)/ Merck Eloctate (Factor VIII)/ Biogen Idec Sivextro (tedisolid phosphate)/Cubist Afrezza (insulin)/ MannKind
Diabetes mellitus, 4/15/2014. FDA approved long-acting GLP type 2 albumin fusion Cardiovascular disease 5/8/2014. FDA approved protease-activated receptor 1 antagonist Hemophilia A 6/6/2014. FDA approved long-acting Factor VIII–Fc fusion Skin and skin-structure 6/20/2014. FDA approved oxazolidinone antibacterial infections biotic for drug-resistant Gram-positive bacteria Diabetes mellitus, 6/27/2014. FDA approved this inhaled insulin type II
Breakthrough drug designation Bexsero/Novartis Meningitis B Mydicar/Celledon
Heart failure
Nivolumab/BMS
Hodgkin lymphoma
Elotuzumab/BMS
Multiple myeloma
CD-1686/Clovis Oncology
Second-line EGFR T790M mutationpositive NSCLC Urothelial bladder cancer Mycobacterial lung disease Antidote for Pradaxa
MMDPL3280A/ Genentech Arikayce/Insmed
Idarucizumab/ Boehringer Ingleheim Blinatumomab/ Acute lymphoblastic Amgen leukemia CTL019/Novartis Relapsed refractory acute lymphoblastic leukemia
Drug information
4/7/2014. Quadrivalent vaccine against meningitis B 4/10/2014. AAV1 gene therapy to replace deficiency in enzyme Serca2A 5/14/2014. Anti-PD-1 monoclonal antibody 5/19/2014. Humanized IgG1 against signaling lymphocyte activation molecule 5/19/2014. Covalent inhibitor of T790M mutant EGFR 5/31/2014. Anti-PDL1 human IgG1 monoclonal antibody with engineered Fc domain 6/19/2014. Inhaled liposomal amikacin 6/25/2014. Humanized Fab fragment targeting Pradaxa 7/1/2014. Bi-specific (CD19/CD3) T-cell engager (BiTE) 7/7/2014. Personalized chimeric antigen receptor T-cell therapy
Notable upcoming regulatory decisions (3Q14)
FDA, US Food and Drug Administration; NSCLC, non–small cell lung cancer. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Drug/company Cobicistat/Gilead
Indication HIV/AIDS
Notable regulatory setbacks (2Q14)
Elvitegravir/Gilead
HIV/AIDS
Lynparza (olaparib)/AstraZeneca Dulaglutide/Eli Lilly Triumeq/GSK
Ovarian cancer
Faridak (panobinostat lactate)/ Novartis Daclatasvir/BMS
Diabetes mellitus, type II HIV/AIDS Multiple myeloma
9/26/2014. US FDA PDUFA for GLP-1–IgG4 Fc fusion 10/22/2014. US FDA PDUFA for HIV integrase inhibitor 11/2/2014. US FDA PDUFA for HDAC inhibitor
12/5/2014. US FDA PDUFA inhibitor of hepatitis C NS5A ABT-450,267,333/ Hepatitis C 12/19/2014. US FDA PDUFA for hepatitis C NS3 AbbVie protease/NS5A protein inhibitor combination Otezla (apremilast)/ Psoriasis 9/23/2014. US FDA PDUFA for phosphodiesterase 4 Celgene inhibitor OBI-1/Baxter Acquired hemo10/10/2014. US FDA PDUFA for recombinant porphilia cine B domain depleted factor VIII HyQvia/Baxter Primary immuno- 9/2/2014. US FDA PDUFA for subcutaneous human deficiencies IgG with recombinant human hyaluronidase Natpara/NPS Hypoparathyroidism 10/24/2014. US FDA PDUFA for recombinant parathyoid hormone Pembrolizumab/ Melanoma 10/28/2014. US FDA PDUFA for humanized IgG4 Merck monoclonal antibody against PD-1 V-503/Merck Human papillo11/1/2014. US FDA PDUFA for this 9-valent mavirus vaccine against HPV Chondrosphere/ Cartilage repair 9/1/2014. EMA decision for in vitro cultured autoloco.don gous cartilage
710
Hepatitis C
Summary 10/3/2014. US FDA PDUFA for cytochrome P450 3A pharmacokinetics enhancer 10/4/2014. US FDA PDUFA for HIV integrase inhibitor 10/3/2014. US FDA PDUFA for PARP inhibitor
Drug/company Indication Vintafolide/ Ovarian Endocyte cancer PEGPH20/ Halozyme
Pancreatic cancer
MetMab (onartuzumab)/ Roche Ipafricept/ OncoMed
Gastric, colorectal, liver cancer
Liver, ovarian, pancreatic cancer Nimotuzumab/ Non–small CIMAB cell lung cancer MAGE-A3/ Non–small GSK cell lung cancer ALD-401/ Ischemic Cytomedix stroke Davunetide/ Endo
Drug information 5/19/2014. Application for market authority withdrawn when the folate-conjugated vinca alkaloid failed to meet progression-free survival endpoint 4/9/2014. Company halted phase 2 trial of pegylated human recombinant hyaluronidase due to excess thrombosis in experimental arm 4/17/2014. Company put advanced clinical trials on hold due to lack of efficacy of anti-Met monoclonal antibody 6/19/2014. Company halted phase 1 trial of small-molecule Wnt inhibitor after bone adverse effects 4/25/2014. Company halted enrollment in phase 3 trial of antiEGFR monoclonal antibody after four patient deaths
4/2/2014. Phase 3 trial halted due to inability to identify patients benefitting from liposomal recombinant MAGE-3 complexed lipid and CpG oligonucleotide 5/6/2014. Program discontinued when stroke patients receiving bone marrow–derived stem cells showed no improvement in phase 2 trial Progressive 5/27/2014. Patients in phase 3 trial showed no improvement with intranasal 8 amino acid peptide fragment of activity-depensupranuclear palsy dent neuroprotective protein
Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Laura DeFrancesco is Senior Editor at Nature Biotechnology.
volume 32 NUMBER 8 AUGUST 2014 nature biotechnology
