data page
Drug pipeline: 4Q14 Laura DeFrancesco The fourth quarter was a busy time at the US Food and Drug Administration (FDA), with a slew of approvals, including the first bispecific antibody and two drugs approved on the same day for idiopathic pulmonary fibrosis, a previously untreatable disease.
Breakthrough drug designations now number 60, with more than a dozen getting through to approval. The first quarter, though, looks to be a quiet one at the FDA, although the European Medicines Agency (EMA) will be looking at some novel cell therapies.
Top ten disease groups by pipeline size
Notable upcoming regulatory decisions (1Q15)
The pipeline for oncology drugs remains the most robust.
Drug/company
Suspended
NDA/BLA
II
Preclinical
III
I
60 85 103 36 3 112 194
Autoimmune/immunology
102 46 66 24 4 53 221
Cardiovascular
75 55 97 36 5 65 204
Endocrine
47 17 27 18 9 31 47
Hematology
221 101 151 49 9 171 269
Infectious disease 26 28 42 19 2 56 63
© 2015 Nature America, Inc. All rights reserved.
Metabolic
npg
Approved
Indication
Drug information
Cosentyx Psoriasis (secukinumab)/Novartis
1/26/2015. EMA approval decision. 1/31/2015. FDA PDUFA review for this IL-17A human IgG1 monoclonal antibody
Empagliflozin/Linagliptin/Diabetes mellitus, Boehringer Ingelheim type II
1/29/2015. FDA PDUFA review of combined SGLT-2 inhibitor with DPP4 inhibitor
Holoclar/Chiesi
Opthalmic wound healing
2/23/2015. EMA approval decision of autologous human corneal epithelial cells expanded ex vivo
TK-DLI/MolMed
Graft-versus-host disease
2/1/2015. EMA approval decision for donor lymphocytes engineered ex vivo via a retrovirus to express herpes simplex virus thymidine kinase
Asfotase alfa/Alexion Pharmaceuticals
Hypophosphatasia
3/1/2015. EU approval decision for engineered recombinant human soluble tissue-nonspecific alkaline phosphatase, the human IgG gamma-1 Fc domain and a mineral-binding deca-aspartate sequence
103 125 144 39 3 222 329
Neurology Oncology 36 29 30 39 5 3 329
Psychiatry
108 368 336 86 7 361 572
Ceftazidime-avibactam/ Urinary, abdominal 2/22/2015. FDA PDUFA first review for this nonActavis and hospital-acquired beta lactam beta-lactamase inhibitor combined with third-generation cephalosporin infections
28 31 58 9 6 42 120
Respiratory
0
500
1,000
1,500
2,000
Number of drugs
Drugs included are biologics, biosimilars, new molecular entities and vaccines. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
PDUFA, Prescription Drug User Fee Act. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Notable regulatory setbacks (4Q14)
Notable regulatory approvals (4Q14)
Drug/company
Drug/company
Indication
Drug information
GSK2586184/GSK Psoriasis
Harvoni (sofosbuvir + ledipasvir)/Gilead
Hepatitis C virus (HCV) (antiviral)
10/10/2014. FDA. Single pill combination of NS5A inhibitor plus polymerase inhibitor
Ofev (nintedanib)/ Boehringer Ingelheim
Idiopathic pulmonary 10/15/2014. FDA. Multigrowth factor and kinase inhibitor for IPF. 12/1/2014. EMA approved for fibrosis (IPF)/nonsmall-cell lung cancer lung cancer
Esbriet (pirfenidone)/ Roche
IPF
10/15/2014. FDA. p38 MAP kinase inhibitor
Lynparza (olaparib)/ AstraZeneca
Ovarian cancer
12/18/2014. EMA. PARP inhibitor
Rapivab (peramivir)/ BioCryst
Influenza therapeutics 12/19/2014. FDA. Single dose, intravenous influenza neuraminidase inhibitor
Opdivo (nivolumab)/ Bristol-Myers Squibb
Melanoma
12/22/2014. FDA. Fully human IgG4 against PD-1
HDAC, histone deacetylase. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Blincyto (blinatumomab)/ Amgen
Acute lymphocytic leukemia
12/3/2014. FDA. Bispecific single-chain Fv (scFv) against CD19 linked via a 15-amino-acid (G4.S1)3 linker to a scFv against CD3
Notable clinical trial results (4Q14) Drug/company
Indication
Trulicity (dulaglutide)/ Eli Lilly
Diabetes mellitus type 1
9/18/2014. FDA. Dipeptidyl peptidase 4 (DPP4)protected glucagon-like peptide-1 analog covalently linked to an IgG4 Fc fragment
Evolocumab/ Amgen
10/2/2014. PCSK9 inhibition led to ~60% decrease in Dyslipidemia/ hypercholester- LDL levels in randomized, double-blind, placebo-controlled phase 2/3 trial. The Lancet doi:10.1016/S0140olemia 6736(14)61399-4 (1 October 2014)
Zarzio (filgrastim)/ Novartis
Neutropenia/ leukopenia
12/8/2014. Phase 3 study of breast cancer patients on chemotherapy showed no difference in the prevention of severe neutropenia between biosimilar and originator product. Blood 124, 21 (2014)
KTE-C19/Kite Pharma
Acute lymphocytic leukemia
10/13/2014. 70% of pediatric or young adults had complete response, 60% reported minimal residual disease. The Lancet doi:10.1016/S0140-6736(14)61403-3 (12 October 2014)
Parkinson’s disease
9/2/2014. Selective seratonin inverse agonist
AP26113/Ariad Pharmaceuticals
Non-small-cell lung cancer
10/2/2014. Anaplastic lymphoma kinase (ALK) inhibitor designed to overcome resistance to another ALK inhibitor from ALK-L1196M mutation
NBI-98854/Neurocrine Tardive dyskinesia Biosciences
10/30/2014. Selective monoamine transporter 2 inhibitor
RBP-8000/Reckitt Benckiser Group
Drug addiction
10/31/2014. Cocaine esterase hydrolyzes cocaine to inactive metabolites
SPK-RPE65/Spark Therapeutics
Leber’s congenital amaurosis
11/6/2014. Gene therapy vector from adenoassociated virus AAV2-hRPE65v2
Dupilumab/Regeneron
Atopic dermatitis
11/20/2014. Antibody that modulates IL-3 and IL-4 in allergic conditions
JCAR015/Juno Therapeutics
Acute lymphocytic leukemia
11/24/2014. Chimeric antigen receptor– modified T cells expressing 19-28zCAR, which binds CD19
MLN9708 (ixazomib citrate)/Takeda
Amyloidosis
12/1/2014. Second-generation proteasome inhibitor
Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Laura DeFrancesco is Senior Editor at Nature Biotechnology.
124
Drug information 11/3/2014. Company suspended development of JAK/ STAT inhibitor after poor risk-benefit profile
Macrilen (macimore- Short stature/growth 11/6/2014. FDA sent a complete response letter for this lin acetate)/AEterna hormone deficiency ghrelin agonist as its pivotal trial did not meet agreed upon end point under special protocol assessment Zentaris Farydak (panobino- Multiple myeloma stat lactate)/Novartis
11/6/2014. FDA Advisory Panel voted against approval of this HDAC inhibitor because of substantial toxicity
Balugrastim/Teva
Neutropenia/ leukopenia
10/30/2014. Company put on hold development of this long-acting biosimilar G-CSF in both the US and EU
TNFa Kinoid/ NeoVacs
Rheumatoid arthritis 12/16/2014. Company suspended phase 2b trial of TNF linked to keyhole limpet hemocyanin, T cell– dependent immunostimulatory protein/adjuvant owing to lack of neutralizing antibody response
Breakthrough drug designations Pimavanserin/Acadia Pharmaceuticals
Indication
Drug information
MA09-hRPE/ Dry age-related Ocata Therapeutics macular degeneration/Stargardt disease
10/15/2014. Phase 1/2 clinical trial of both patient groups showed tolerability after 12 months and vision-related improvements in quality of life. Lancet doi: 10.1016/ S0140-6736(14)61376-3. (October 15, 2014)
CTL019/Novartis
Acute lymphocytic leukemia
10/16/2014. 27 patients (90%) in phase 1 trial had complete response, 67% had sustained remission, 75% overall survival. N. Engl. J. Med. 371, 1507–1517 (2014)
NSI-566/ Neuralstem
Amyotrophic 10/22/2014. Study of spinal cord–derived neural stem lateral sclerosis cells in six autopsies showed survival of transplant 2.5 years after placement. Ann. Clin. Transplant. Neurol. 1, 900–908 (2014)
ISIS-FXIRx/Isis Pharmaceuticals
Anticoagulation 12/7/2014. In phase 2 trial, factor IX antisense at higher dose showed superiority to standard of care in preventing venous thrombosis in patients undergoing knee arthroplasty. New Engl. J. Med. doi:10.1056/NEJMoa1405760 (7 December 2014)
Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
volume 33 NUMBER 2 FEBRUARY 2015 nature biotechnology
Drug pipeline: 4Q14 Laura DeFrancesco The fourth quarter was a busy time at the US Food and Drug Administration (FDA), with a slew of approvals, including the first bispecific antibody and two drugs approved on the same day for idiopathic pulmonary fibrosis, a previously untreatable disease.
Breakthrough drug designations now number 60, with more than a dozen getting through to approval. The first quarter, though, looks to be a quiet one at the FDA, although the European Medicines Agency (EMA) will be looking at some novel cell therapies.
Top ten disease groups by pipeline size
Notable upcoming regulatory decisions (1Q15)
The pipeline for oncology drugs remains the most robust.
Drug/company
Suspended
NDA/BLA
II
Preclinical
III
I
60 85 103 36 3 112 194
Autoimmune/immunology
102 46 66 24 4 53 221
Cardiovascular
75 55 97 36 5 65 204
Endocrine
47 17 27 18 9 31 47
Hematology
221 101 151 49 9 171 269
Infectious disease 26 28 42 19 2 56 63
© 2015 Nature America, Inc. All rights reserved.
Metabolic
npg
Approved
Indication
Drug information
Cosentyx Psoriasis (secukinumab)/Novartis
1/26/2015. EMA approval decision. 1/31/2015. FDA PDUFA review for this IL-17A human IgG1 monoclonal antibody
Empagliflozin/Linagliptin/Diabetes mellitus, Boehringer Ingelheim type II
1/29/2015. FDA PDUFA review of combined SGLT-2 inhibitor with DPP4 inhibitor
Holoclar/Chiesi
Opthalmic wound healing
2/23/2015. EMA approval decision of autologous human corneal epithelial cells expanded ex vivo
TK-DLI/MolMed
Graft-versus-host disease
2/1/2015. EMA approval decision for donor lymphocytes engineered ex vivo via a retrovirus to express herpes simplex virus thymidine kinase
Asfotase alfa/Alexion Pharmaceuticals
Hypophosphatasia
3/1/2015. EU approval decision for engineered recombinant human soluble tissue-nonspecific alkaline phosphatase, the human IgG gamma-1 Fc domain and a mineral-binding deca-aspartate sequence
103 125 144 39 3 222 329
Neurology Oncology 36 29 30 39 5 3 329
Psychiatry
108 368 336 86 7 361 572
Ceftazidime-avibactam/ Urinary, abdominal 2/22/2015. FDA PDUFA first review for this nonActavis and hospital-acquired beta lactam beta-lactamase inhibitor combined with third-generation cephalosporin infections
28 31 58 9 6 42 120
Respiratory
0
500
1,000
1,500
2,000
Number of drugs
Drugs included are biologics, biosimilars, new molecular entities and vaccines. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
PDUFA, Prescription Drug User Fee Act. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Notable regulatory setbacks (4Q14)
Notable regulatory approvals (4Q14)
Drug/company
Drug/company
Indication
Drug information
GSK2586184/GSK Psoriasis
Harvoni (sofosbuvir + ledipasvir)/Gilead
Hepatitis C virus (HCV) (antiviral)
10/10/2014. FDA. Single pill combination of NS5A inhibitor plus polymerase inhibitor
Ofev (nintedanib)/ Boehringer Ingelheim
Idiopathic pulmonary 10/15/2014. FDA. Multigrowth factor and kinase inhibitor for IPF. 12/1/2014. EMA approved for fibrosis (IPF)/nonsmall-cell lung cancer lung cancer
Esbriet (pirfenidone)/ Roche
IPF
10/15/2014. FDA. p38 MAP kinase inhibitor
Lynparza (olaparib)/ AstraZeneca
Ovarian cancer
12/18/2014. EMA. PARP inhibitor
Rapivab (peramivir)/ BioCryst
Influenza therapeutics 12/19/2014. FDA. Single dose, intravenous influenza neuraminidase inhibitor
Opdivo (nivolumab)/ Bristol-Myers Squibb
Melanoma
12/22/2014. FDA. Fully human IgG4 against PD-1
HDAC, histone deacetylase. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Blincyto (blinatumomab)/ Amgen
Acute lymphocytic leukemia
12/3/2014. FDA. Bispecific single-chain Fv (scFv) against CD19 linked via a 15-amino-acid (G4.S1)3 linker to a scFv against CD3
Notable clinical trial results (4Q14) Drug/company
Indication
Trulicity (dulaglutide)/ Eli Lilly
Diabetes mellitus type 1
9/18/2014. FDA. Dipeptidyl peptidase 4 (DPP4)protected glucagon-like peptide-1 analog covalently linked to an IgG4 Fc fragment
Evolocumab/ Amgen
10/2/2014. PCSK9 inhibition led to ~60% decrease in Dyslipidemia/ hypercholester- LDL levels in randomized, double-blind, placebo-controlled phase 2/3 trial. The Lancet doi:10.1016/S0140olemia 6736(14)61399-4 (1 October 2014)
Zarzio (filgrastim)/ Novartis
Neutropenia/ leukopenia
12/8/2014. Phase 3 study of breast cancer patients on chemotherapy showed no difference in the prevention of severe neutropenia between biosimilar and originator product. Blood 124, 21 (2014)
KTE-C19/Kite Pharma
Acute lymphocytic leukemia
10/13/2014. 70% of pediatric or young adults had complete response, 60% reported minimal residual disease. The Lancet doi:10.1016/S0140-6736(14)61403-3 (12 October 2014)
Parkinson’s disease
9/2/2014. Selective seratonin inverse agonist
AP26113/Ariad Pharmaceuticals
Non-small-cell lung cancer
10/2/2014. Anaplastic lymphoma kinase (ALK) inhibitor designed to overcome resistance to another ALK inhibitor from ALK-L1196M mutation
NBI-98854/Neurocrine Tardive dyskinesia Biosciences
10/30/2014. Selective monoamine transporter 2 inhibitor
RBP-8000/Reckitt Benckiser Group
Drug addiction
10/31/2014. Cocaine esterase hydrolyzes cocaine to inactive metabolites
SPK-RPE65/Spark Therapeutics
Leber’s congenital amaurosis
11/6/2014. Gene therapy vector from adenoassociated virus AAV2-hRPE65v2
Dupilumab/Regeneron
Atopic dermatitis
11/20/2014. Antibody that modulates IL-3 and IL-4 in allergic conditions
JCAR015/Juno Therapeutics
Acute lymphocytic leukemia
11/24/2014. Chimeric antigen receptor– modified T cells expressing 19-28zCAR, which binds CD19
MLN9708 (ixazomib citrate)/Takeda
Amyloidosis
12/1/2014. Second-generation proteasome inhibitor
Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
Laura DeFrancesco is Senior Editor at Nature Biotechnology.
124
Drug information 11/3/2014. Company suspended development of JAK/ STAT inhibitor after poor risk-benefit profile
Macrilen (macimore- Short stature/growth 11/6/2014. FDA sent a complete response letter for this lin acetate)/AEterna hormone deficiency ghrelin agonist as its pivotal trial did not meet agreed upon end point under special protocol assessment Zentaris Farydak (panobino- Multiple myeloma stat lactate)/Novartis
11/6/2014. FDA Advisory Panel voted against approval of this HDAC inhibitor because of substantial toxicity
Balugrastim/Teva
Neutropenia/ leukopenia
10/30/2014. Company put on hold development of this long-acting biosimilar G-CSF in both the US and EU
TNFa Kinoid/ NeoVacs
Rheumatoid arthritis 12/16/2014. Company suspended phase 2b trial of TNF linked to keyhole limpet hemocyanin, T cell– dependent immunostimulatory protein/adjuvant owing to lack of neutralizing antibody response
Breakthrough drug designations Pimavanserin/Acadia Pharmaceuticals
Indication
Drug information
MA09-hRPE/ Dry age-related Ocata Therapeutics macular degeneration/Stargardt disease
10/15/2014. Phase 1/2 clinical trial of both patient groups showed tolerability after 12 months and vision-related improvements in quality of life. Lancet doi: 10.1016/ S0140-6736(14)61376-3. (October 15, 2014)
CTL019/Novartis
Acute lymphocytic leukemia
10/16/2014. 27 patients (90%) in phase 1 trial had complete response, 67% had sustained remission, 75% overall survival. N. Engl. J. Med. 371, 1507–1517 (2014)
NSI-566/ Neuralstem
Amyotrophic 10/22/2014. Study of spinal cord–derived neural stem lateral sclerosis cells in six autopsies showed survival of transplant 2.5 years after placement. Ann. Clin. Transplant. Neurol. 1, 900–908 (2014)
ISIS-FXIRx/Isis Pharmaceuticals
Anticoagulation 12/7/2014. In phase 2 trial, factor IX antisense at higher dose showed superiority to standard of care in preventing venous thrombosis in patients undergoing knee arthroplasty. New Engl. J. Med. doi:10.1056/NEJMoa1405760 (7 December 2014)
Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com/).
volume 33 NUMBER 2 FEBRUARY 2015 nature biotechnology
