Global Cancer Immunotherapy Market Analysis and Forecast to 2023
Global Cancer Immunotherapy Market Analysis and Forecast to 2023
Abstract
Immunotherapy is forecast to become the oncology treatment of choice by 2026 with an estimated 60% of previously treated cancer patients likely to adopt immunotherapy in this timeframe. Multiple treatment lines, combination therapy and the opportunity for repeat treatment are likely to accelerate fast growth. Cancer immunotherapy also expands into multiple indications and our analysis indicates that key immunotherapies including anti-PD-1 drugs, dendritic cell vaccines, T-cell therapies and cancer vaccines are all driving the market. The rising incidence and prevalence of numerous cancers globally is a significant accelerator of growth. This is due to more sensitive early detection techniques, higher patient awareness and a growing aging population. Furthermore, the FDA’s pro-science attitude will accelerate development and regulatory approval for these drugs. To that end, the cancer immunotherapy market is forecast to hit $115 billion by 2023. Overall strong growth rates are expected due to a significant unmet need and increasing trends of hematological cancers.
Prior to the launching of Yervoy, the five-year survival rate for patients with early stage melanoma was 98%; but the five-year survival rate for late-stage melanoma was just 16%. Yervoy has been reported to have a survival rate of 25% when tested alone. When tested as part of a combination therapy treatment with Bristol’s nivolumab, the two-year survival rates rose to 88% for patients with late-stage cancer. Increase in patient survival rates brought about by cancer immunotherapy treatment is similar to that seen when bone marrow transplantation changed our conception on how blood cancer was treated. Other key therapeutic players in this market include Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), Ibrance (palbociclib) the newly approved Bavencio (avelumab) and Imfinzi (durvalumab) and of course the first CAR-T therapies Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel).
Opdivo (nivolumab) from BMS is one of the most exciting agents in the immunotherapy space, and is indicated for melanoma, lung cancer, kidney cancer, blood cancer, head and neck cancer, and bladder cancer. It was given a fast-track approval on December 22, 2014. The majority of immune-oncology agents are anti-programmed death-1 (PD-1) monoclonal antibodies, which will certainly guide the market over the coming years. Projects that currently are valuable include combined immunotherapies on our knowledge of CD137 and PD-1/PDL1 mechanisms. A study on a novel effector activating monoclonal antibody known as IMAB362 for the treatment of solid cancers is also exciting. Other projects comparing CAR-T cell effectiveness against T-cells that target CD19 or mesothelin are interesting in a preclinical setting. Of course, Novartis gained the first CAR-T FDA approval for Kymriah (tisagenlecleucel, CTL019), in August 2017, for children and young adults with B-cell ALL. In October 2017, Yescarta (axicabtagene ciloleucel) from Kite Pharma for adult patients large B-cell lymphoma was also given FDA approval. This is a major boost for the global and US immunotherapy, and gene therapy markets.
What Are CAR-T Therapies? How Will They Impact the Market?
CAR T (chimeric antigen receptor T) cells are engineered specificity using antibody fragments directed to the tumor cell, and also T-cell CD8/CD3 plasma membrane proteins that elicit specific activity towards the tumor cell, via intracellular signaling pathways. To date publications have revealed a number of effective intracellular molecules in the engineered T cell including CD28, 4-1BB (CD137) and CD3 zeta.
These engineered T cells have numerous advantages including:
•Intracellular domain can be modified to increase efficacy and durability of CAR-T
•CAR-T are still subject to the same regulatory and tolerogenic constraints of natural T cells, including checkpoints, Treg, MDSC
•CAR-T can be engineered to express cytokines and chemokines that further enhance function and migration
•Can be modified to express suicide genes that limit CAR-T population if toxicity occurs
To date, the main challenges associated with CAR T therapy include manufacturing, regulations, pricing and toxicity in patients. Currently there are over 100 recruiting CAR-T clinical trials globally, mainly in the US, China and Europe. To date a number of CAR T Cells (autologous/allogeneic) trials are demonstrating clinical benefit to patients, but others have demonstrated toxicity such as cytokine release syndrome. In July 2017, an FDA advisory panel determined that the benefits of CAR T outperform the risks. Kymriah (tisagenlecleucel) by Novartis is indicated to treat children and young adults with acute leukemia and performed well in the ELIANA trial. The FDA’s Oncologic Drugs Advisory Committee (ODAC) recommended this agent for approval and became the first CAR-T cell therapy on the US market. In October 2017, Yescarta (axicabtagene ciloleucel) from Kite Pharma for adult patients large B-cell lymphoma was also given FDA approval.
The CAR-T industry is addressing unmet needs in specific relapsed cancers, and trials have indicated that some patients show long term activity and high remission rates, but there is a large proportion of patients with toxicities such as cytokine release syndrome and neurotoxicity. The main players within the CAR-T market are Novartis, Juno Therapeutics, Kite Pharma and Cellectis. The market is moving ahead, backed by years of R&D, from both academia and industry, investors capitol and small clinical studies. From now on, Kelly Scientific forecasts that CAR T therapy will become more streamlined, with faster manufacturing times as advances in technologies take hold and clinical trials provide more robust evidence that this immunotherapy is robust. These factors, plus strategies to reduce adverse reactions and toxicities and larger players like Novartis taking stage will push CAR-T therapy ahead. However, recent deaths in the Juno ROCKET trial are creating questions amongst investors. How will the CAR T space influence the total immunotherapy industry going forward? This comprehensive report scrutinizes the total market and provides cutting-edge insights and analysis.
Content
Table of Contents
1.0 Executive Summary
1.1 Objectives of Report
1.2 Key Questions Answered in this Report
1.3 Data Sources and Methodology
2.0 Cancer Immunotherapy: An Overview
2.1 Human Immune System
2.1.1 Components of Human Immune System
2.2 Types of Cancer Immunotherapy
2.3 Monoclonal Antibodies (Mabs) to Treat Cancer
2.3.1 Most Frequently Targeted Antigens by MAbs
2.4 Types of Monoclonal Antibodies (MAbs)
2.4.1 Naked MAbs
2.4.2 Conjugated Monoclonal Antibodies
2.4.2.1 Components of an Antibody Drug Conjugate (ADC)
2.4.2.2 Mechanism of Action of Antibody Drug Conjugate (ADC)
2.4.2.3 The Cytotoxic Wareheads used in ADCs
2.4.2.4 Successful Cytotoxin Wareheads
2.4.2.5 Developmental Timeline of ADCs
2.4.2.6 Target Antigens for ADCs in Preclinical and Clinical Development
2.4.2.7 Important Clinical Assets in ADCs
2.4.3 Bispecific Monoclonal Antibodies
2.4.3.1 Technology Platforms for the Production of Bispecific MAbs
2.4.4 Safety and Side Effects of MAbs in Cancer Immunotherapy
2.5 Cancer Vaccines
2.5.1 Cancer Vaccines in Development
2.6 Non-Specific Cancer Immunotherapies and Adjuvants
2.6.1 Cytokines
2.6.2 Interferon (IFN)
2.7 New Frontiers in Cancer Immunotherapy Research
2.7.1 Drugs for Targeting Immune Checkpoints
2.7.1.1 Cytotoxic T-Lymphocyte-Associated Protein-4 (CTLA-4)
2.7.1.2 Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1)
2.7.1.3 Major Checkpoint Inhibitors in Clinical Development
2.7.2 Chimeric Antigen Receptor (CAR) T Cell Therapy
2.7.3 Tumor-Infiltrating Lymphocytes (TILs) and Interleukin-2 (IL-2)
2.8 Cancer Immunotherapy: Timeline of Progress
3.0 Current Status of Cancer Immunotherapy: An Overview
3.1 Programmed Death (PD-1) Inhibitors
3.1.1 Important Events and Advantages for Nivolumab in Melanoma Indication
3.1.2 Important Events and Advantages for Nivolumab in Non-Small Cell Lung Cancer
3.1.3 Important Events and Advantages for Nivolumab in Renal Cell Cancer
3.1.4 Nivolumab Studies for Melanoma
3.1.5 Nivolumab Studies for Non-Small Cell Lung Cancer (NSCLC)
3.1.6 Nivolumab Studies for Renal Cell Cancer (RCC)
3.2 Keytruda (Pembrolizumab, MK-3475)
3.2.1 Important Events and Advantages for Keytruda in Melanoma
3.2.2 Important Events and Advantages for Keytruda in NSCLC
3.2.3 Important Events for Keytruda in RCC
3.3 Tecentriq from Roche
3.3.1 Important Events for Tecentriq in Melanoma
3.3.2 Important Events and Advantages for Tecentriq in NSCLC
3.3.3 Important Event for Tecentriq in RCC
3.3.4 Tecentriq Studies in NSCLC
3.3.5 Tecentriq Studies in RCC
3.3.6 Tecentriq Study in RCC
3.4 Pidilizumab from CureTech
3.5 An Overview of Anti-PD-1 Clinical Development
3.5.1 Other Checkpoint Inhibitors in Development
3.6 Studies with Yervoy (Ipilimumab)
3.7 Studies with Tremelimumab
3.8 KAHR-102
3.9 TIM3 Antibody
3.10 BMS-989016
3.11 ImmuTune IMP701 and ImmuFact IMP321
3.12 Dendritic Cell Therapies
3.12.1 Provenge (Sipuleucel-T)
3.12.2 AGS-003 from Argos Therapeutics
3.12.3 DCP-001 from DCPrime
3.12.4 DC-Vax from Northwest Biotherapeutics
3.13 Chimeric Antigen Receptor T-Cells (CAR-T) Therapies
3.13.1 CLT109
3.13.2 Chimeric Antigen Receptors (CAR) Program by Juno
3.13.3 Chimeric Antigen Receptor (CAR) T-Cell Program by Bluebird Bio
3.13.4 UCART19 from Cellectis
3.13.5 Chimeric Immune Receptor (CIR) T-Cells from Abramson Cancer Center
3.13.6 CD19 eACT CAR-T Therapy from Kite Pharma
3.13.7 Autologous CAR-T Program for Breast Cancer from Adaptimmune
3.14 Cancer Vaccines
3.14.1 HyperAcute
3.14.2 MAGE-A3 Antigen-Specific Cancer Immunotherapeutic
3.14.3 ADXS-HPV
3.14.4 IDO Inhibitors
3.14.5 Indoximod and NLG-919 (INCY)
3.14.6 INCB24360 (INCY)
3.14.7 deCellVax (BMSN)
3.15 Miscellaneous Immunotherapies
3.15.1 Contego (Lion Biotechnologies)
3.15.2 TG4010 (Transgene)
3.16 Most Valuable R&D Projects in Cancer Immunotherapy
3.16.1 Nivolumab (Opdivo)
3.16.2 Keytruda
3.16.3 Tecentriq
3.16.4 Palbociclib
3.16.5 DCVax-L
3.16.6 Imfinzi
4.0 Challenges in Cancer Medicine Research: An Overview
4.1 Years of Failures and Emerging Successes in Melanoma Medicine Research
4.1.1 Future Outlook for Melanoma Drugs
4.2 A New Era for Lung Cancer Medicines
4.2.1 Progresses Made in Lung Cancer Medicine Research
4.2.2 Successes and Failures in Lung Cancer Medicine Development
4.2.3 Future Outlook for Lung Cancer Medicines
4.3 Ray of Hope for Brain Cancer Patients
4.3.1 Progress made for Brain Cancer Treatment in Recent Years
4.3.2 Successes and Failures in Brain Cancer Drug Development
5.0 Cancer Immunotherapeutic Products: An Overview
5.1 I-Labelled Tositumomab (Bexxar)
5.2 Y-Labelled Ibritumomab (Zevalin)
5.3 Alemtuzumab (Campath)
5.4 Adotrastuzumab Emtansine (Kadcyla)
5.5 Bacillus Calmette-Guerin (BCG)
5.6 Bevacizumab (Avastin)
5.7 Brentuximab Vedotin (Adcetris)
5.8 Cetuximab (Erbitux)
5.9 Cervarix
5.10 DenileukinDiftitox (Ontak)
5.11 Gardasil
5.12 Gemtuzumab (Mylotarg)
5.13 Hepatitis B Vaccine
5.14 Interferon Alfa (IFN-alfa)
5.15 Interleukin-2 (IL-2)
5.16 Ipilimumab (Yervoy)
5.17 Ofatumumab (Arzerra)
5.18 Panitumumab (Vectibix)
5.19 Pembrolizumab (Keytruda)
5.20 Rituximab (Mabthera)
5.21 Sargramostim (Leukine)
5.22 Sipuleucel-T (Provenge)
5.23 Trastuzumab (Herceptin)
6.0 Available Immunotherapies for Cancer by Disease Type: An Overview
6.1 Melanoma Skin Cancer and Immunotherapy
6.1.1 Ipilimumab (Yervoy) for Advanced Melanoma
6.1.2 PD-1 Inhibitors (Keytruda and Opdivo) for Advanced Melanoma
6.1.3 Cytokines for Advanced Melanoma
6.1.4 Interferon Alfa as Adjuvant Therapy for Melanoma
6.1.5 Bacille Calmette-Guerin (BCG) Vaccine for Melanoma
6.1.6 Imiquimod (zyclara) Cream for Melanoma
6.2 Breast Cancer and Immunotherapy
6.2.1 Promising Therapeutic Vaccine Product Candidates for Breast Cancer
6.2.2 Promising Checkpoint Inhibiting Product Candidates for Breast Cancer
6.2.3 Promising Adoptive T Cell Therapy Product Candidates for Breast Cancer
6.2.4 Promising Antibody Product Candidates for Breast Cancer
6.3 Immunotherapy for Prostate Cancer
6.3.1 Therapeutic Vaccines for Prostate Cancer
6.3.2 Checkpoint Inhibitors for Prostate Cancer
6.3.3 Adoptive Cell Therapy for Prostate Cancer
6.4 Immunotherapy for Lung Cancer
6.4.1 Monoclonal Antibodies for Lung Cancer
6.4.1.1 Promising MAb Product Candidates for Lung Cancer
6.4.1.2 Checkpoint Inhibitors for Lung Cancer
6.4.1.3 Therapeutic Vaccines for Lung Cancer
6.4.1.4 Promising Adoptive T Cell Transfer Product Candidates for Lung Cancer
6.5 Immunotherapy for Colorectal Cancer
6.5.1 Promising Monoclonal Antibody Product Candidates for Colorectal Cancer
6.5.2 Trials Using Checkpoint Inhibitors and Immune Modulators for Colorectal Cancer
6.5.3 Clinical Trials for Vaccines Indicated for Colorectal Cancer
6.5.4 Adoptive Cell Therapy for Colorectal Cancer
6.5.5 Oncolytic Virus Therapy for Colorectal Cancer
6.5.6 Adjuvant Immunotherapy for Colorectal Cancer
6.5.7 Cytokines for Colorectal Cancer
6.6 Immunotherapies in Development for Lymphoma
6.6.1 Therapeutic Vaccines in Development for Lymphoma
6.6.2 Checkpoint Inhibitors for Lymphoma
6.6.3 Adoptive T Cell Transfer for Lymphoma
6.6.4 Monoclonal Antibodies for Lymphoma
6.7 Immunotherapy for Kidney Cancer
6.7.1 Checkpoint Inhibitors for Kidney Cancer
6.7.2 Vaccines for Kidney Cancer
6.7.3 Adoptive Cell Therapy for Kidney Cancer
6.8 Dominance of MAbs and Vaccines in Cancer Clinical Research
6.9 Oncology Biologics Losing Patent Protection
7.0 Cancer Incidence and Mortality: An Overview
7.1 Global Economic Burden of Cancer
7.2 Global Burden of Cancer
7.3 Top Five Most Frequent Cancers, Globally
7.3.1 Global Prevalence of Colorectal, Breast and Lung Cancers
7.3.2 Percentage of Top Three Cancers Diagnosed Globally
7.3.2.1 Mortality due to Lung, Liver and Stomach Cancers
7.3.2.2 Percentage of Death due to Lung, Liver and Stomach Cancers
7.4 Cancer Deaths in Women
7.5 Prevalence and Mortality for Cancer Types Addressed by Immunotherapy
7.5.1 Breast Cancer
7.5.1.1 Worldwide Incidence of Breast Cancer and Mortality Rate by Geography
7.5.1.2 Female Breast Cancer Incidence in the U.S
7.5.1.3 Five Year Breast Cancer Survival Rates by Stage at Diagnosis and Age in the U.S
7.5.1.4 Breast Cancer Incidence in Canada
7.5.1.5 Breast Cancer Incidence and Mortality in Latin America
7.5.1.6 Breast Cancer Incidence and Mortality in Europe
7.5.1.7 Breast Cancer Incidence in Asia/Pacific
7.5.1.8 Breast Cancer Incidence by Country
7.5.2 Gastric Cancer (Stomach Cancer)
7.5.2.1 Incidence of Gastric Cancer in Top 15 Countries
7.5.3 Colorectal Cancer
7.5.3.1 Global Incidence of Colorectal Cancer
7.5.3.2 Worldwide Variations in the Incidence of Colorectal Cancer
7.5.3.3 Risk Factors for Colorectal Cancer
7.5.3.4 Colorectal Cancer Screening in the U.S
7.5.3.5 Colorectal Cancer Incidence Rates in the U.S. by State
7.5.3.6 Colorectal Cancer Mortality Rates (per 100,000) in the U.S. by States
7.5.4 Lung Cancer
7.5.4.1 Non-Small Cell Lung Cancer (NSCLC)
7.5.4.2 Global NSCLC Incidence
7.5.4.3 Lung Cancer in Americas by Gender
7.5.4.4 Tobacco Use and Lung Cancer
7.5.4.5 Current Therapeutic Options for Lung Cancer
7.5.5 Glioblastoma
7.5.5.1 Global Incidence of Glioblastoma
7.5.6 Kidney Cancer
7.5.6.1 Global Incidence of Kidney Cancer
7.5.7 Blood Cancer
7.5.7.1 Leukemia
7.5.7.2 Blood Cancer in the U.S
7.5.8 Cervical Cancer
7.5.8.1 Global Incidence of Cervical Cancer
7.5.9 Prostate Cancer
7.5.9.1 Global Incidence of Prostate Cancer
7.5.9.2 Prostate Cancer Incidence and Mortality by Geography
7.5.9.3 Prostrate Cancer in the U. S
7.5.10 Melanoma
7.5.10.1 Skin Cancer in the U. S
8.0 Global Oncology Market Analysis and Forecast to 2023
8.1 Global Oncology Market Geographical Analysis and Forecast to 2023
8.2 Top Companies in Oncology Drug Sales
8.2.1 Roche
8.2.2 Novartis
8.2.3 Pfizer
8.2.4 Bristol-Myers Squibb
8.2.5 Merck
8.2.6 Celgene
8.2.7 AstraZeneca
8.2.8 Eli Lilly
8.2.9 Takeda
8.3 FDA approved oncology drugs to 2019
8.4 Top Oncology Drug Market Forecast to 2023
8.5 Global Oncology Therapeutics Market by Cancer Type
9.0 Market for Cancer Immunotherapy
9.1 Key Drivers
9.2 Global Market for Cancer Immunotherapeutics by Geography
9.3 Global Market for Cancer Immunotherapy by Product Class
9.4 Global Market for Immunotherapy Drugs by Cancer Type
9.5 Global Market for Monoclonal Antibodies for Cancer by Type
9.5.1 Best Selling MAbs
9.5.1.1 Market Forecast for Herceptin
9.5.1.2 Market Value and Forecast for Avastin
9.5.1.3 Global Market and forecast for Erbitux
9.5.1.4 Global Market and Forecast for Yervoy
9.5.1.5 Global Market and Forecast for Mabthera
9.5.1.6Global Market and Forecast ForOpdivo (Nivolumab)
9.5.2 Global Market and Forecast for Antibody Drug Conjugates (ADCs)
9.5.2.1 Global Market and Forecast for Adcetris
9.5.2.2 Global Market and Forecast for Keytruda
9.6 Global Market and Forecast for Cancer Vaccines
9.6.1 Global Market for Cancer Vaccines by Type
9.7 Global Market for Non-Specific Cancer Immunotherapeutics
9.7.1 High Cost of MAbs
10.0 Company Profiles
10.1 Ablynx NV
10.2 Activartis Biotech GmbH
10.2.1 GBM Vax Study
10.3 Advaxis Inc
10.3.1 Advaxis’ Technology
10.3.2 Advaxis’ Product Pipeline
10.3.2.1 ADXS-HPV
10.3.2.2 ADXS-PSA
10.3.2.3 ADXS-cHER2
10.4 AduroBioTech Inc
10.4.1 Aduro’s Technology
10.4.1.1 CRS-207
10.4.1.2 AUD-623
10.4.1.3 ADU-741
10.4.1.4 ADU-S100
10.5 Agenus Inc
10.5.1 QS-21 Stimulon
10.6 AlphaVax Inc
10.6.1 Alpha Vax’s Technology
10.7 A. MenariniIndustrieFarmaceuticheRiuniteSrl
10.7.1 MEN1112
10.8 Amgen Inc
10.8.1 Vectibix (panitumumab)
10.8.2 Blinatumomab (Blincyto)
10.8.3 Rilotumumab
10.9 Antigen Express Inc
10.9.1 Li-Key Hybrid Vaccines (AE37)
10.10 Argos Therapeutics Inc
10.10.1 AGS-003
10.11 Bavarian Nordic A/S
10.11.1 Prostvac
10.11.2 CV-301
10.11.3 MVA-BN PRP
10.11.4 MVA-BN HER2
10.11.4.1 MVA-BN Brachyury
10.12 Bellicum Pharmaceuticals Inc
10.12.1 BPX-501
10.12.2 BPX-201
10.12.3 BPX-401
10.12.4 BPX-601
10.12.5 BPX-701
10.13 Biogen Idec Inc
10.13.1 Rituxan (Rituximab)
10.13.2 Gazyva (Obinutuzumab)
10.14 Biovest International Inc
10.14.1 BiovaxID
10.15 Bristol-Myers Squibb Company
10.15.1 Erbitux (cetuximab)
10.15.2 OPDIVO (nivolumab)
10.15.3 Yervoy (ipilimumab)
10.16 Cellectis
10.17 Cellerant Therapeutics Inc
10.17.1 CLT-008
10.17.2 CLT-009
10.18 Celldex Therapeutics
10.18.1 Rindopepimut
10.18.2 Glembatumumabvedotin (CDX-011)
10.18.3 Varlilumab (CDX-1127)
10.18.4 CDX-1401
10.18.5 CDX-301
10.19 CEL-SCI Corp.
10.19.1 Multikine
10.20 CureTech Ltd.
10.20.1 Pidilizumab (CT-011)
10.21 Delta-Vir GmbH
10.21.1 Treatment
10.22 Dendreon Corp.
10.22.1 Provenge (Sipuleucel-T)
10.23 DenDrit Biotech USA
10.23.1 MelCancerVac
10.24 DNAtrix Inc
10.24.1 DNX-2401
10.25 Eli Lilly and Co.
10.25.1 Erbitux (Cetuximab)
10.26 EMD Serono Inc
10.27 Etubics Corp.
10.28 Galena Biopharma Inc
10.29 Genentech Inc
10.29.1 Avastin (bevacizumab) for Metastatic Colorectal Cancer
10.29.1.1 Avastin and Interferon Alfa for Metastatic Kidney Cancer
10.29.1.2 Avastin for Metastatic NLCLC
10.29.2 Gazyva (obinutuzumab) for Chronic Lymphocytic Leukemia
10.29.3 Herceptin (trastuzumab) for Breast Cancer
10.29.3.1 Herceptin and Chemotherapy for Gastric Cancer
10.29.4 Kadcyla (ado-trastuzumab emtansine)
10.29.5 Perjeta (pertuzumab)
10.29.6 Rituxan (rituximab)
10.29.7 Genentech’s Cancer Immunotherapy Pipeline Products
10.30 Genmab AS
10.30.1 Ofatumumab
10.31 GlaxoSmithKline
10.31.1 Arzerra (Ofatumumab)
10.31.2 Cervarix
10.32 Gliknik Inc
10.33 GlobeImmune Inc
10.34 Heat Biologics Inc
10.35 Immatics Biotechnologies GmbH
10.36 ImmunoCellular Therapeutics Ltd.
10.37 Immunocore Ltd.
10.37.1 Product Pipeline
10.38 ImmunoFrontier Inc
10.39 ImmunoGen Inc
10.39.1 IMGN853
10.39.2 IMGN529
10.39.3 IMGN289
10.39.4 IMGN779
10.40 Immunomedics Inc
10.41 Immunotope Inc
10.41.1 IMT-1012 Immunotherapeutic Vaccine
10.42 Immunovaccine Inc
10.43 Inovio Pharmaceuticals Inc
10.44 Janssen Biotech Inc
10.44.1 Doxil
10.44.2 Procrit
10.44.3 Zytiga
10.44.4 Imbruvicia
10.45 Juno Therapeutics Inc
10.46 Kite Pharma Inc
10.46.1 Kite Pharma’s Technology
10.46.1.1 eACT (engineered Autologous Cell Therapy)
10.46.1.2 DC-Ad GM-CAIX
10.47 MabVax Therapeutics Holdings Inc
10.48 MedImmune LLC
10.49 Merck & Co., Inc
10.49.1 Gardasil (Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine
10.49.2 Keytruda (Pembrolizumab)
10.50 Merrimack Pharmaceuticals Inc
10.51 Morphotek Inc
10.51.1 Farletuzumab (MORAb-003)
10.51.2 Amatuximab (MORAb-009)
10.51.3 Ontuxizumab (MORAb-004)
10.51.4 MORAb-066
10.52 NewLink Genetics Corp.
10.53 Northwest Biotherapeutics Inc
10.54 NovaRx Corp.
10.55 OncoPep Inc
10.55.1 PVX-410
10.56 Oncothyreon Inc
10.57 OSE Pharma SA
10.58 Oxford BioTherapeutics Ltd.
10.58.1 Technologies
10.58.1.1 OGAP – Cancer Targeting
10.58.1.2 Antibody Development
10.58.1.3 Antibody “arming”
10.58.2 Lead Programs
10.58.2.1 OX001/MEN1112
10.58.2.2 OX002
10.58.2.3 OX003
10.58.2.4 OX004
10.59 Pique Therapeutics
10.60 Polynoma LLC
10.60.1 MAVIS Trial
10.61 Prima BioMed Ltd.
10.62 Progenics Pharmaceuticals Inc
10.62.1 PSMA Targeted Imaging Compound (1404)
10.62.2 PSMA ADC Therapeutic
10.62.3 Small Molecule Therapeutic (1095)
10.62.4 Azedra
10.63 Regen Biopharma Inc
10.63.1 HemaXellerate
10.63.2 dCellVax
10.63.3 Diffron C
10.64 Roche Holdings Inc
10.64.1 Avastin (Bevacizumab)
10.64.2 Gazyva/Gazyvaro (Obinutuzumab; GA101)
10.64.3 Herceptin (Trastuzumab)
10.64.4 Kadcyla (Trastuzumabumemtansinum)
10.64.5 Mabthera (Rituximab)
10.64.6 Perjeta (Pertuzumab)
10.65 Seattle Genetics Inc
10.65.1 Adcetris (Brentuximab vedotin)
10.65.2 Seattle Genetics’ Collaborarator Pipeline
10.66 Sorrento Therapeutics Inc
10.66.1 Sorrento’s Antibody Technologies
10.66.1.1 G-MAB
10.66.1.2 Antibody Drug Conjugates (ADCs)
10.67 Spectrum Pharmaceuticals Inc
10.67.1 Zevalin
10.68 Synthon Pharmaceuticals Inc
10.69 TapImmune Inc
10.70 ThioLogics Ltd.
10.71 Transgene SA
10.72 TVAX Biomedical Inc
10.72.1 TVI-Brain-1
10.72.2 TVI-Kidney-1
10.73 Vaccinogen Inc
10.74 Viventia Biotechnologies Inc
10.75 Wilex AG
10.76 Ziopharm Oncology Inc
11.0 Cancer Immunotherapy Market Participants by Product Segment
12.0 CAR T Therapy
12.1 Challenges Relating to Chimeric Antigen Receptor T Cells in Immunotherapy
12.1.1 Clinical Status of CD19 CAR-T Cells To Date
12.1.2 Clinical and Regulatory Challenges for Development of CAR T Cells
12.1.3 Key Regulatory Challenges Associated with CAR-T Development
12.1.4 Summary of Select CAR-T Products by Juno, Novartis and Kite
12.1.5 Clinical Benefit Versus Toxicity in CD19-Directed ALL Clinical Trials
12.1.6 How to Manage Toxicity of CAR-T Therapy
13.0 Regulations Pertaining to Immunotherapy Regulation in the USA
13.1 Center for Biologics Evaluation and Research (CBER)
13.1.1 Compliance and Surveillance
13.1.2 Extra Resources on Immunotherapeutics from the FDA
13.1.3 Cellular, Tissue and Gene Therapies Advisory Committee
13.1.4 Consumer Affairs Branch (CBER) Contact in FDA
13.1.5 FDA Regulations Pertaining to Immunotherapies
13.1.6 Case Study Ovarian Cancer Immunotherapy Regulations
13.1.6.1 Efficacy
13.1.6.2 Adverse Effects
13.1.7 Trial Design Considerations for Immunotherapy
13.1.8 Development of Immune-Related Response Criteria (irRC) & Clinical Endpoints Specific to Immunotherapies
14.0 Regulations for Immunotherapy in Japan
14.1 PMDA and Immunotherapy
14.1.1 Increasing the Efficiency in Immunotherapy Regulatory Review
14.1.2 Forerunner Review Assignment System
14.1.3 Revised Guidelines for Clinical Evaluation of Anti‐Malignant Tumor Agents
14.1.4 Key Contacts Within the PMDA for Immunotherapeutics
15.0 European Regulation and Immunotherapeutics
15.1 Introduction
15.2 Challenges for Immunotherapy in EMEA
15.2.1 EMA Status on Potency Testing
15.2.1.1 In Vivo Potency Testing
15.2.1.2 In Vitro Potency Testing
15.2.1.3 Viable Cell Count
15.2.1.4 Autologous Cell Based Products
15.2.1.5 Reference Preparation
15.2.1.6 Adjuvant Containing Immunotherapy Products
15.2.2 EMA Status on Identifying hyper, Hypo or non-Responders
15.3 Challenges Relating to Biomarkers in Immunotherapy
15.4 Challenges Relating to Chimeric Antigen Receptor T Cells in Immunotherapy
15.5 Estimating Optimal Cut-Off Parameters
15.6 EU-Approved Immunotherapies in Melanoma
15.7 Key Contacts Within EMA for Immunotherapeutics
16.0 Manufacturing of Immunotherapies
16.1 Introduction
16.2 Generation of CAR-Modified T Cells
16.2.1 What Co-Stimulation and Activity Domain is Optimal to Use?
16.2.2 Optimizing Cell Culture Media
16.2.3 Manufacturing Lentiviral Vectors
16.2.4 Detection of Integrated CAR-Expressing Vectors
16.2.5 Donor Lymphocyte Infusion Procedure
16.2.6 Ex Vivo Costimulation& Expansion of Donor T Cells
16.2.7 Infusion to the Patient
16.3 Manufacturing Devices and Instruments Required for Immunotherapy Production
16.3.1 Leukapheresis
16.3.2 Cell Counters and Analyzer
16.3.3 Cell Seeding, Growth and Propagation
16.4 Good Manufacturing Procedure (GMP) for Immunotherapy
16.5 Case Study Production of Lentivirus Induced Dendritic Cells under GMP Conditions
16.6 Quality Control
16.7 Regulatory Affairs
16.8 Key Challenges in Manufacturing
16.8.1 Electroporation of T-cells
16.8.2 Allogenic CAR T cells
16.8.3 Relapse Rates are Critical
16.8.4 Antigen Negative Relapse
16.8.5 Incorporating Suicide Genes
16.8.16 Automation in Cell Therapy Manufacturing
16.8.17 Autologous Cell Therapy Manufacture Scale Up
17.0 Supply Chain & Logistics
17.1 Introduction
17.2 Case Study: Juno Therapeutics
18.0 Pricing & Cost Analysis
18.1 Introduction
18.2 CAR T Therapy Market Evaluation
19.0 Current Deals Within the CAR T Market
20.0 CAR T Therapy Company Case Studies
20.1 Juno Therapeutics
20.2 Kite Pharma
20.3 Cellectis
Appendix
Immuno-Oncology Highlights and Approvals over the last number of years
Future Directions of Immuno-Oncology
List of Tables
Table 2.1: Types of Immune Cells and their Functions
Table 2.2: FDA-Approved Cancer Immunotherapies
Table 2.3: FDA-Approved Monoclonal Antibodies (MAbs) to Treat Cancer
Table 2.4: Most Frequently Targeted Antigens by MAbs
Table 2.5: FDA-Approved Monoclonal Antibodies
Table 2.6: Cytotoxic Wareheads Used in ADCs
Table 2.7: Targeted Indications for ADCs
Table 2.8: Antibody Drug Conjugates: Developmental Tmeline
Table 2.9: Target Antigens for ADCs in Preclinical and Clinical Development
Table 2.10: Current ADCs Launched, Withdrawn and in Phase I/II/III Trials by Sponsor, Indication, Antigen, Cytotoxin and Linker
Table 2.11: MAb Products and Candidates that Recruit T Cells
Table 2.12: Bispecific MAbs in Clinical Trials Targeting Cancer by Indication and Company
Table 2.13: Bispecific Antibody Technology Platforms
Table 2.14: Side Effects of Some of the Approved Cancer Immunotherapy MAbs
Table 2.15: FDA-Approved Cancer Vaccines
Table 2.16: Cancer Vaccines in Development
Table 2.17: FDA-Approved Cytokines for Cancer Immunotherapy
Table 2.18: Cancer Indications Approved for IFN-alfa
Table 2.19: FDA-Approved Immune Checkpoint Modulators
Table 2.20: Immune Checkpoint Inhibitors in Clinical Development
Table 2.21: Cancer Immunotherapy: Timeline of Progress
Table 3.1: PD-1 Therapies Targeting either the PD-L1/L2 or PD-1 Receptor
Table 3.2: Overview of Clinical Trial Landscape for Top Five Anti-PD-1 and Anti-PD-L1 Drugs
Table 3.3: Nivolumab Efficacy from Expansion Cohorts of Study 003
Table 3.4: Key Clinical Trial Data of Pembrolizumab in Melanoma
Table 3.5: IMpower132 Phase III Data of Tecentriq, (atezolizumab RG7446) in NSCLC Patients
Table 3.6: Phase III IMmotion151 study results of Roche's Tecentriq (atezolizumab) and Avastin (bevacizumab) in Renal Cell Carcinoma
Table 3.7: Phase I Melanoma Data for Tecentriq
Table 3.8: Phase II Data for Pidilizumab in Diffuse Large B Cell Lymphoma (DLBCL)
Table 3.9: Phase II Melanoma Data for Pidilizumab
Table 3.10: An Overview of Anti-PD-1 Development by Company, Drug Candidate, Indication and Clinical Phase
Table 3.11: Clinical Development of CTLA-4, TIM3, and LAG3 Checkpoint Inhibitors by Company, Drug Candidate, Indication and Clinical Trial Stage
Table 3.12: Pivotal Phase III Results for Yervoy in Second-Line Patients with Metastatic Melanoma
Table 3.13: Updated Data from Phase III Clinical Study 024 for Yervoy
Table 3.14: Data from the Failed Phase III Study of Tremelimumab for Melanoma
Table 3.15: An Overview of Clinical Development of Dendritic Cell Therapies by Company, Drug Candidate, Indication and Clinical Phase
Table 3.16: Pivotal Phase III Results for Yervoy in Second-Line Patients with Metastatic Melanoma
Table 3.17: Phase I/Iia Results from Kite Pharma’s CAR-T Therapy
Table 3.18: Cancer Vaccines in Development by Company, Drug Candidate, Indication & Clinical Phase
Table 3.19: Advaxis Phase II Results for Cervical Cancer Patients in India
Table 3.20: Phase II Data for Contego
Table 3.21: Valuable R&D Projects in Cancer Immunotherapy
Table 6.1: Cancer Types Addressed by Immunotherapies by Drug, Trade Name and Company
Table 6.2: Oncology Drugs Losing Patent Protection by 2020 by Product, U.S. Expiry Date and E.U. Expiry Date
Table 7.1: Global Cancer Statistics – Key Facts
Table 7.2: Top Five Most Frequent Cancers, Globally
Table 7.3: Estimated Breast Cancer Cases and Deaths in the U.S. by Age
Table 7.4: Estimated Canadian Breast Cancer Statistics
Table 7.5: Age-Standardized Breast Cancer Incidence Rate per 100,000 Women by Country
Table 7.6: Global Colorectal Cancer Incidence and Mortality Rates by Gender per 100,000 people
Table 7.7: Risk Factors for Colorectal Cancer
Table 7.8: Lung Cancer Incidence and Mortality Rate in Americas by Gender
Table 7.9: Current Therapeutic Options for Lung Cancer
Table 7.10: Estimated Number of New Leukemia Cases in the U.S.
Table 7.11: Estimated Deaths in the U.S. from Leukemia
Table 7.12: Estimated Deaths from HL and NHL in the U.S.
Table 7.13: Estimated Incidence and Deaths for Myeloma in the U.S.
Table 7.14 Global Prostate Cancer Incidence and Mortality Rates by Geography
Table 7.15: Incidence and Mortality Rates of Prostate Cancer in Americas
Table 7.16: Incidence and Mortality Rates for Melanoma in Americas
Table 8.1: Global Market for Oncology Drugs by Geography/Country, Through 2023
Table 8.2: Top Ten Companies in Oncology Sales, Through 2023
Table 8.3: Top Five Oncology Drugs, Through 2023
Table 9.1: Global Cancer Immunotherapy Market, Through 2023
Table 9.2: Global Market for Immunotherapy by Product Class, Through 2023
Table 9.3: Global Market for Immunotherapy Drugs by Cancer Type, Through 2023
Table 9.4: Global Market for Monoclonal Antibodies for Cancer by Type, Through 2023
Table 9.5: Global and U.S. Market for Herceptin, Through 2023
Table 9.6: Global and U.S. Market for Avastin, Through 2023
Table 9.7: Global Market for Cancer Vaccines, Through 2023
Table 9.8: Global Market for Cancer Vaccines by Type, Through 2023
Table 9.9: Projected Market for the Forthcoming DCVax-L and Imfinzi
Table 9.10: Annual Cost of MAbs in the U.S. by Product, Indication and Biomarker
Table 10.1: Ablynx’s Product Pipeline
Table 10.2: Aduro’s Product Pipeline
Table 10.3: Agenus’ Product Pipeline
Table 10.4: AlphaVax Cancer Immunology Product Pipeline
Table 10.5: Amgen’s Product Pipeline
Table 10.6: Antigen Express’ Cancer Therapeutic Pipeline
Table 10.7: Argos’ Cancer Product Pipeline
Table 10.8: Bavarian Nordic’s Product Pipenine
Table 10.9: Bellicum’s Pipeline Product Candidatea
Table 10.10: Biogen’s Oncology Pipeline
Table 10.11: Bristol-Myers Squibb’s Pipeline Products in Cancer Immunotherapy
Table 10.12: Cellectis’ Products in Development
Table 10.13: Cellerant’s Product Pipeline
Table 10.14: Celldex’s Therapeutic Pipeline
Table 10.15: CEL-SCI’s Immunotherapy Products in Development
Table 10.16: EMD Serono’s Product Pipeline
Table 10.17: Etubic’s Product Pipeline
Table 10.18: Galena’s Product Pipeline
Table 10.19: Genentech’s Cancer Immunotherapy Pipeline Products
Table 10.20: Genmab’s Products in Development
Table 10.21: Gliknik’s Product Pipeline
Table 10.22: GlobeImmune’s Product Pipeline
Table 10.23: Heat Biologic’s Product Pipeline
Table 10.24: Immatics Biotechnology’s Product Pipeline
Table 10.25: ImmunoCellular’s Product Pipeline
Table 10.26: Immunomedics’ Late-Stage Antibody-Based Therapies
Table 10.27: Immunovaccine’s Product Pipeline
Table 10.28: Inovio Pharmaceuticals Product Pipeline
Table 10.29: Juno Therapeutics’ Current Pipeline
Table 10.30: Kite Pharma’s Product Pipeline
Table 10.31: MabVax’s Product Pipeline
Table 10.32: MedImmune’s Products in Development
Table 10.33: Merck’s Pipeline of Cancer Immunotherapy Products
Table 10.34: Merrimack’s Product Pipeline
Table 10.35: NewLink Genetics’ Product Pipeline
Table 10.36: Northwest’s Product Pipeline
Table 10.37: NovaRx Clinical Development Pipeline
Table 10.38: Oncothyreon’s Immunotherapy Product Pipeline
Table 10.39: OSE Pharma’s Product Pipeline
Table 10.40: Pique Therapeutics’ Product Pipeline
Table 10.41: Prima BioMed’s Pipeline
Table 10.42: Progenics Pharmaceutical’s Pipeline
Table 10.43: Roche Holding’s Cancer Immunotherapy Product Pipeline
Table 10.44: Seattle Genetics’ Pipeline Products
Table 10.45: Seattle Genetics’ Collaborarator Pipeline
Table 10.46: Synthon Biopharmaceuticals’ Pipeline
Table 10.47: TapImmune’s Product Pipeline
Table 10.48: ThioLogic’s Product Pipeline
Table 10.49: Transgene’s Product Pipeline
Table 10.50: Vaccinogen’s Product Pipeline
Table 10.51: Viventia’s Product Pipeline
Table 10.52: Wilex’s Product Pipeline
Table 10.53: Ziopharm’s Products in Development
Table 11.1: Cancer Immunotherapy Market Participants by Product Segment
Table 12.1: Selected CD19-directed Product Candidates in Clinical Trials by Costimulatory & Binding Domains, Starting Cell Population, Vector and Ablation Technology
Table 12.2: Select CD19-Directed ALL Clinical Trials
Table 12.3: Select Anti-CD22 CAR-T Clinical Projects
Table 13.1: CBER Compliance and Surveillance Activities
Table 13.2: Contacts for the Cellular, Tissue and Gene Therapies Advisory Committee, FDA
Table 14.1: Key Contacts Within PMDA, Japan
Table 15.1: Contact Details for EMA Immunotherapy Experts
Table 16.1: General Technical and Personnel Requirements of a GMP, QC, QA, FDA Regulated Cell Therapy Manufacturing Facility
Table 16.2: Technician/Scientific Requirements for CAR T Manufacturing
Table 16.3: Selection of Apheresis Instruments Currently on the Market
Table 16.4: Selection of Cell Counters and Analyzer Instruments Currently on the Market
Table 16.5: Main Objectives of GMP Manufacturing Immunotherapeutics
Table 16.6: Main Objectives of Quality Control While Manufacturing Immunotherapeutics
Table 16.7: Main Objectives of Regulatory Affairs During Manufacturing Immunotherapeutics
Table 16.8: CAR-T Studies Using mRNA Transfection Electroporation
Table 16.9: Challenges for Autologous Cell Therapy Manufacture
Table 16.10: Current Company/Institutions with Suicide Gene CAR T Projects
Table 16.11: Advantages of Using Automated Cell Therapy Manufacturing
Table 16.12: Main Drivers to Implement Automated Cell Therapy Manufacturing
Table 16.13: Main Benefits of Automated Cell Therapy Manufacturing
Table 16.14: Advantages & Disadvantages of Autologous Cell Therapy Manufacture Scale Up
Table 17.1: Juno Therapeutics Manufacturing Facility Objectives
Table 18.1: Current Juno Therapeutics Trials and CAR T Products
Table 19.1: Current CAR T Business Deals
Table 20.1: Juno Therapeutics Target Biomarker Portfolio
Table 20.2 Juno Therapeutics CAR Technology
Table 20.3 Juno Therapeutics T Cell Receptor (TCR) Technology
Table 20.4 Juno Therapeutics Clinical Pipeline by Target, Product and Trial
Table 20.5: Select CD19-Directed ALL Clinical Trials
Table 20.6: Select Anti-CD22 CAR-T Clinical Projects
Table 20.7 Juno Therapeutics Manufacturing Facility Objectives
Table 20.8 Current Kite Pharma CAR T Clinical Studies and Trials
Table 20.9 Current Kite Pharma TCR Clinical Studies and Trials
List of Figures
Figure 2.1: Components of an Antibody Drug Conjugate (ADC)
Figure 2.2: Mechanism of Action of Antibody Drug Conjugates
Figure 2.3: Ranking of Commonly Used Cytotoxin Wareheads
Figure 4.1: Number of Successful and Unsuccessful Melanoma Drugs
Figure 4.2: Successes and Failures in Lung Cancer Medicine Development
Figure 4.3: Successes and Failures in Brain Cancer Drug Development
Figure 5.1: Ibritumomab Linked to Yttrium Radfionucleotide
Figure 5.2: Kadcyla (Trastuzumab + DMI)
Figure 6.1: Dominance of MAbs and Vaccines in Cancer Clinical Research
Figure 7.1: Global Economic Burden of Cancer
Figure 7.2: Number of Colorectal, Breast and Lung Cancer Cases Diagnosed Globally
Figure 7.3 Percentage of Top Three Cancers Diagnosed Globally
Figure 7.4: Number of Deaths due to Lung, Liver and Stomach Cancers Globally
Figure 7.5: Perce
Prior to the launching of Yervoy, the five-year survival rate for patients with early stage melanoma was 98%; but the five-year survival rate for late-stage melanoma was just 16%. Yervoy has been reported to have a survival rate of 25% when tested alone. When tested as part of a combination therapy treatment with Bristol’s nivolumab, the two-year survival rates rose to 88% for patients with late-stage cancer. Increase in patient survival rates brought about by cancer immunotherapy treatment is similar to that seen when bone marrow transplantation changed our conception on how blood cancer was treated. Other key therapeutic players in this market include Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), Ibrance (palbociclib) the newly approved Bavencio (avelumab) and Imfinzi (durvalumab) and of course the first CAR-T therapies Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel).
Opdivo (nivolumab) from BMS is one of the most exciting agents in the immunotherapy space, and is indicated for melanoma, lung cancer, kidney cancer, blood cancer, head and neck cancer, and bladder cancer. It was given a fast-track approval on December 22, 2014. The majority of immune-oncology agents are anti-programmed death-1 (PD-1) monoclonal antibodies, which will certainly guide the market over the coming years. Projects that currently are valuable include combined immunotherapies on our knowledge of CD137 and PD-1/PDL1 mechanisms. A study on a novel effector activating monoclonal antibody known as IMAB362 for the treatment of solid cancers is also exciting. Other projects comparing CAR-T cell effectiveness against T-cells that target CD19 or mesothelin are interesting in a preclinical setting. Of course, Novartis gained the first CAR-T FDA approval for Kymriah (tisagenlecleucel, CTL019), in August 2017, for children and young adults with B-cell ALL. In October 2017, Yescarta (axicabtagene ciloleucel) from Kite Pharma for adult patients large B-cell lymphoma was also given FDA approval. This is a major boost for the global and US immunotherapy, and gene therapy markets.
What Are CAR-T Therapies? How Will They Impact the Market?
CAR T (chimeric antigen receptor T) cells are engineered specificity using antibody fragments directed to the tumor cell, and also T-cell CD8/CD3 plasma membrane proteins that elicit specific activity towards the tumor cell, via intracellular signaling pathways. To date publications have revealed a number of effective intracellular molecules in the engineered T cell including CD28, 4-1BB (CD137) and CD3 zeta.
These engineered T cells have numerous advantages including:
•Intracellular domain can be modified to increase efficacy and durability of CAR-T
•CAR-T are still subject to the same regulatory and tolerogenic constraints of natural T cells, including checkpoints, Treg, MDSC
•CAR-T can be engineered to express cytokines and chemokines that further enhance function and migration
•Can be modified to express suicide genes that limit CAR-T population if toxicity occurs
To date, the main challenges associated with CAR T therapy include manufacturing, regulations, pricing and toxicity in patients. Currently there are over 100 recruiting CAR-T clinical trials globally, mainly in the US, China and Europe. To date a number of CAR T Cells (autologous/allogeneic) trials are demonstrating clinical benefit to patients, but others have demonstrated toxicity such as cytokine release syndrome. In July 2017, an FDA advisory panel determined that the benefits of CAR T outperform the risks. Kymriah (tisagenlecleucel) by Novartis is indicated to treat children and young adults with acute leukemia and performed well in the ELIANA trial. The FDA’s Oncologic Drugs Advisory Committee (ODAC) recommended this agent for approval and became the first CAR-T cell therapy on the US market. In October 2017, Yescarta (axicabtagene ciloleucel) from Kite Pharma for adult patients large B-cell lymphoma was also given FDA approval.
The CAR-T industry is addressing unmet needs in specific relapsed cancers, and trials have indicated that some patients show long term activity and high remission rates, but there is a large proportion of patients with toxicities such as cytokine release syndrome and neurotoxicity. The main players within the CAR-T market are Novartis, Juno Therapeutics, Kite Pharma and Cellectis. The market is moving ahead, backed by years of R&D, from both academia and industry, investors capitol and small clinical studies. From now on, Kelly Scientific forecasts that CAR T therapy will become more streamlined, with faster manufacturing times as advances in technologies take hold and clinical trials provide more robust evidence that this immunotherapy is robust. These factors, plus strategies to reduce adverse reactions and toxicities and larger players like Novartis taking stage will push CAR-T therapy ahead. However, recent deaths in the Juno ROCKET trial are creating questions amongst investors. How will the CAR T space influence the total immunotherapy industry going forward? This comprehensive report scrutinizes the total market and provides cutting-edge insights and analysis.
1.0 Executive Summary
1.1 Objectives of Report
1.2 Key Questions Answered in this Report
1.3 Data Sources and Methodology
2.0 Cancer Immunotherapy: An Overview
2.1 Human Immune System
2.1.1 Components of Human Immune System
2.2 Types of Cancer Immunotherapy
2.3 Monoclonal Antibodies (Mabs) to Treat Cancer
2.3.1 Most Frequently Targeted Antigens by MAbs
2.4 Types of Monoclonal Antibodies (MAbs)
2.4.1 Naked MAbs
2.4.2 Conjugated Monoclonal Antibodies
2.4.2.1 Components of an Antibody Drug Conjugate (ADC)
2.4.2.2 Mechanism of Action of Antibody Drug Conjugate (ADC)
2.4.2.3 The Cytotoxic Wareheads used in ADCs
2.4.2.4 Successful Cytotoxin Wareheads
2.4.2.5 Developmental Timeline of ADCs
2.4.2.6 Target Antigens for ADCs in Preclinical and Clinical Development
2.4.2.7 Important Clinical Assets in ADCs
2.4.3 Bispecific Monoclonal Antibodies
2.4.3.1 Technology Platforms for the Production of Bispecific MAbs
2.4.4 Safety and Side Effects of MAbs in Cancer Immunotherapy
2.5 Cancer Vaccines
2.5.1 Cancer Vaccines in Development
2.6 Non-Specific Cancer Immunotherapies and Adjuvants
2.6.1 Cytokines
2.6.2 Interferon (IFN)
2.7 New Frontiers in Cancer Immunotherapy Research
2.7.1 Drugs for Targeting Immune Checkpoints
2.7.1.1 Cytotoxic T-Lymphocyte-Associated Protein-4 (CTLA-4)
2.7.1.2 Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1)
2.7.1.3 Major Checkpoint Inhibitors in Clinical Development
2.7.2 Chimeric Antigen Receptor (CAR) T Cell Therapy
2.7.3 Tumor-Infiltrating Lymphocytes (TILs) and Interleukin-2 (IL-2)
2.8 Cancer Immunotherapy: Timeline of Progress
3.0 Current Status of Cancer Immunotherapy: An Overview
3.1 Programmed Death (PD-1) Inhibitors
3.1.1 Important Events and Advantages for Nivolumab in Melanoma Indication
3.1.2 Important Events and Advantages for Nivolumab in Non-Small Cell Lung Cancer
3.1.3 Important Events and Advantages for Nivolumab in Renal Cell Cancer
3.1.4 Nivolumab Studies for Melanoma
3.1.5 Nivolumab Studies for Non-Small Cell Lung Cancer (NSCLC)
3.1.6 Nivolumab Studies for Renal Cell Cancer (RCC)
3.2 Keytruda (Pembrolizumab, MK-3475)
3.2.1 Important Events and Advantages for Keytruda in Melanoma
3.2.2 Important Events and Advantages for Keytruda in NSCLC
3.2.3 Important Events for Keytruda in RCC
3.3 Tecentriq from Roche
3.3.1 Important Events for Tecentriq in Melanoma
3.3.2 Important Events and Advantages for Tecentriq in NSCLC
3.3.3 Important Event for Tecentriq in RCC
3.3.4 Tecentriq Studies in NSCLC
3.3.5 Tecentriq Studies in RCC
3.3.6 Tecentriq Study in RCC
3.4 Pidilizumab from CureTech
3.5 An Overview of Anti-PD-1 Clinical Development
3.5.1 Other Checkpoint Inhibitors in Development
3.6 Studies with Yervoy (Ipilimumab)
3.7 Studies with Tremelimumab
3.8 KAHR-102
3.9 TIM3 Antibody
3.10 BMS-989016
3.11 ImmuTune IMP701 and ImmuFact IMP321
3.12 Dendritic Cell Therapies
3.12.1 Provenge (Sipuleucel-T)
3.12.2 AGS-003 from Argos Therapeutics
3.12.3 DCP-001 from DCPrime
3.12.4 DC-Vax from Northwest Biotherapeutics
3.13 Chimeric Antigen Receptor T-Cells (CAR-T) Therapies
3.13.1 CLT109
3.13.2 Chimeric Antigen Receptors (CAR) Program by Juno
3.13.3 Chimeric Antigen Receptor (CAR) T-Cell Program by Bluebird Bio
3.13.4 UCART19 from Cellectis
3.13.5 Chimeric Immune Receptor (CIR) T-Cells from Abramson Cancer Center
3.13.6 CD19 eACT CAR-T Therapy from Kite Pharma
3.13.7 Autologous CAR-T Program for Breast Cancer from Adaptimmune
3.14 Cancer Vaccines
3.14.1 HyperAcute
3.14.2 MAGE-A3 Antigen-Specific Cancer Immunotherapeutic
3.14.3 ADXS-HPV
3.14.4 IDO Inhibitors
3.14.5 Indoximod and NLG-919 (INCY)
3.14.6 INCB24360 (INCY)
3.14.7 deCellVax (BMSN)
3.15 Miscellaneous Immunotherapies
3.15.1 Contego (Lion Biotechnologies)
3.15.2 TG4010 (Transgene)
3.16 Most Valuable R&D Projects in Cancer Immunotherapy
3.16.1 Nivolumab (Opdivo)
3.16.2 Keytruda
3.16.3 Tecentriq
3.16.4 Palbociclib
3.16.5 DCVax-L
3.16.6 Imfinzi
4.0 Challenges in Cancer Medicine Research: An Overview
4.1 Years of Failures and Emerging Successes in Melanoma Medicine Research
4.1.1 Future Outlook for Melanoma Drugs
4.2 A New Era for Lung Cancer Medicines
4.2.1 Progresses Made in Lung Cancer Medicine Research
4.2.2 Successes and Failures in Lung Cancer Medicine Development
4.2.3 Future Outlook for Lung Cancer Medicines
4.3 Ray of Hope for Brain Cancer Patients
4.3.1 Progress made for Brain Cancer Treatment in Recent Years
4.3.2 Successes and Failures in Brain Cancer Drug Development
5.0 Cancer Immunotherapeutic Products: An Overview
5.1 I-Labelled Tositumomab (Bexxar)
5.2 Y-Labelled Ibritumomab (Zevalin)
5.3 Alemtuzumab (Campath)
5.4 Adotrastuzumab Emtansine (Kadcyla)
5.5 Bacillus Calmette-Guerin (BCG)
5.6 Bevacizumab (Avastin)
5.7 Brentuximab Vedotin (Adcetris)
5.8 Cetuximab (Erbitux)
5.9 Cervarix
5.10 DenileukinDiftitox (Ontak)
5.11 Gardasil
5.12 Gemtuzumab (Mylotarg)
5.13 Hepatitis B Vaccine
5.14 Interferon Alfa (IFN-alfa)
5.15 Interleukin-2 (IL-2)
5.16 Ipilimumab (Yervoy)
5.17 Ofatumumab (Arzerra)
5.18 Panitumumab (Vectibix)
5.19 Pembrolizumab (Keytruda)
5.20 Rituximab (Mabthera)
5.21 Sargramostim (Leukine)
5.22 Sipuleucel-T (Provenge)
5.23 Trastuzumab (Herceptin)
6.0 Available Immunotherapies for Cancer by Disease Type: An Overview
6.1 Melanoma Skin Cancer and Immunotherapy
6.1.1 Ipilimumab (Yervoy) for Advanced Melanoma
6.1.2 PD-1 Inhibitors (Keytruda and Opdivo) for Advanced Melanoma
6.1.3 Cytokines for Advanced Melanoma
6.1.4 Interferon Alfa as Adjuvant Therapy for Melanoma
6.1.5 Bacille Calmette-Guerin (BCG) Vaccine for Melanoma
6.1.6 Imiquimod (zyclara) Cream for Melanoma
6.2 Breast Cancer and Immunotherapy
6.2.1 Promising Therapeutic Vaccine Product Candidates for Breast Cancer
6.2.2 Promising Checkpoint Inhibiting Product Candidates for Breast Cancer
6.2.3 Promising Adoptive T Cell Therapy Product Candidates for Breast Cancer
6.2.4 Promising Antibody Product Candidates for Breast Cancer
6.3 Immunotherapy for Prostate Cancer
6.3.1 Therapeutic Vaccines for Prostate Cancer
6.3.2 Checkpoint Inhibitors for Prostate Cancer
6.3.3 Adoptive Cell Therapy for Prostate Cancer
6.4 Immunotherapy for Lung Cancer
6.4.1 Monoclonal Antibodies for Lung Cancer
6.4.1.1 Promising MAb Product Candidates for Lung Cancer
6.4.1.2 Checkpoint Inhibitors for Lung Cancer
6.4.1.3 Therapeutic Vaccines for Lung Cancer
6.4.1.4 Promising Adoptive T Cell Transfer Product Candidates for Lung Cancer
6.5 Immunotherapy for Colorectal Cancer
6.5.1 Promising Monoclonal Antibody Product Candidates for Colorectal Cancer
6.5.2 Trials Using Checkpoint Inhibitors and Immune Modulators for Colorectal Cancer
6.5.3 Clinical Trials for Vaccines Indicated for Colorectal Cancer
6.5.4 Adoptive Cell Therapy for Colorectal Cancer
6.5.5 Oncolytic Virus Therapy for Colorectal Cancer
6.5.6 Adjuvant Immunotherapy for Colorectal Cancer
6.5.7 Cytokines for Colorectal Cancer
6.6 Immunotherapies in Development for Lymphoma
6.6.1 Therapeutic Vaccines in Development for Lymphoma
6.6.2 Checkpoint Inhibitors for Lymphoma
6.6.3 Adoptive T Cell Transfer for Lymphoma
6.6.4 Monoclonal Antibodies for Lymphoma
6.7 Immunotherapy for Kidney Cancer
6.7.1 Checkpoint Inhibitors for Kidney Cancer
6.7.2 Vaccines for Kidney Cancer
6.7.3 Adoptive Cell Therapy for Kidney Cancer
6.8 Dominance of MAbs and Vaccines in Cancer Clinical Research
6.9 Oncology Biologics Losing Patent Protection
7.0 Cancer Incidence and Mortality: An Overview
7.1 Global Economic Burden of Cancer
7.2 Global Burden of Cancer
7.3 Top Five Most Frequent Cancers, Globally
7.3.1 Global Prevalence of Colorectal, Breast and Lung Cancers
7.3.2 Percentage of Top Three Cancers Diagnosed Globally
7.3.2.1 Mortality due to Lung, Liver and Stomach Cancers
7.3.2.2 Percentage of Death due to Lung, Liver and Stomach Cancers
7.4 Cancer Deaths in Women
7.5 Prevalence and Mortality for Cancer Types Addressed by Immunotherapy
7.5.1 Breast Cancer
7.5.1.1 Worldwide Incidence of Breast Cancer and Mortality Rate by Geography
7.5.1.2 Female Breast Cancer Incidence in the U.S
7.5.1.3 Five Year Breast Cancer Survival Rates by Stage at Diagnosis and Age in the U.S
7.5.1.4 Breast Cancer Incidence in Canada
7.5.1.5 Breast Cancer Incidence and Mortality in Latin America
7.5.1.6 Breast Cancer Incidence and Mortality in Europe
7.5.1.7 Breast Cancer Incidence in Asia/Pacific
7.5.1.8 Breast Cancer Incidence by Country
7.5.2 Gastric Cancer (Stomach Cancer)
7.5.2.1 Incidence of Gastric Cancer in Top 15 Countries
7.5.3 Colorectal Cancer
7.5.3.1 Global Incidence of Colorectal Cancer
7.5.3.2 Worldwide Variations in the Incidence of Colorectal Cancer
7.5.3.3 Risk Factors for Colorectal Cancer
7.5.3.4 Colorectal Cancer Screening in the U.S
7.5.3.5 Colorectal Cancer Incidence Rates in the U.S. by State
7.5.3.6 Colorectal Cancer Mortality Rates (per 100,000) in the U.S. by States
7.5.4 Lung Cancer
7.5.4.1 Non-Small Cell Lung Cancer (NSCLC)
7.5.4.2 Global NSCLC Incidence
7.5.4.3 Lung Cancer in Americas by Gender
7.5.4.4 Tobacco Use and Lung Cancer
7.5.4.5 Current Therapeutic Options for Lung Cancer
7.5.5 Glioblastoma
7.5.5.1 Global Incidence of Glioblastoma
7.5.6 Kidney Cancer
7.5.6.1 Global Incidence of Kidney Cancer
7.5.7 Blood Cancer
7.5.7.1 Leukemia
7.5.7.2 Blood Cancer in the U.S
7.5.8 Cervical Cancer
7.5.8.1 Global Incidence of Cervical Cancer
7.5.9 Prostate Cancer
7.5.9.1 Global Incidence of Prostate Cancer
7.5.9.2 Prostate Cancer Incidence and Mortality by Geography
7.5.9.3 Prostrate Cancer in the U. S
7.5.10 Melanoma
7.5.10.1 Skin Cancer in the U. S
8.0 Global Oncology Market Analysis and Forecast to 2023
8.1 Global Oncology Market Geographical Analysis and Forecast to 2023
8.2 Top Companies in Oncology Drug Sales
8.2.1 Roche
8.2.2 Novartis
8.2.3 Pfizer
8.2.4 Bristol-Myers Squibb
8.2.5 Merck
8.2.6 Celgene
8.2.7 AstraZeneca
8.2.8 Eli Lilly
8.2.9 Takeda
8.3 FDA approved oncology drugs to 2019
8.4 Top Oncology Drug Market Forecast to 2023
8.5 Global Oncology Therapeutics Market by Cancer Type
9.0 Market for Cancer Immunotherapy
9.1 Key Drivers
9.2 Global Market for Cancer Immunotherapeutics by Geography
9.3 Global Market for Cancer Immunotherapy by Product Class
9.4 Global Market for Immunotherapy Drugs by Cancer Type
9.5 Global Market for Monoclonal Antibodies for Cancer by Type
9.5.1 Best Selling MAbs
9.5.1.1 Market Forecast for Herceptin
9.5.1.2 Market Value and Forecast for Avastin
9.5.1.3 Global Market and forecast for Erbitux
9.5.1.4 Global Market and Forecast for Yervoy
9.5.1.5 Global Market and Forecast for Mabthera
9.5.1.6Global Market and Forecast ForOpdivo (Nivolumab)
9.5.2 Global Market and Forecast for Antibody Drug Conjugates (ADCs)
9.5.2.1 Global Market and Forecast for Adcetris
9.5.2.2 Global Market and Forecast for Keytruda
9.6 Global Market and Forecast for Cancer Vaccines
9.6.1 Global Market for Cancer Vaccines by Type
9.7 Global Market for Non-Specific Cancer Immunotherapeutics
9.7.1 High Cost of MAbs
10.0 Company Profiles
10.1 Ablynx NV
10.2 Activartis Biotech GmbH
10.2.1 GBM Vax Study
10.3 Advaxis Inc
10.3.1 Advaxis’ Technology
10.3.2 Advaxis’ Product Pipeline
10.3.2.1 ADXS-HPV
10.3.2.2 ADXS-PSA
10.3.2.3 ADXS-cHER2
10.4 AduroBioTech Inc
10.4.1 Aduro’s Technology
10.4.1.1 CRS-207
10.4.1.2 AUD-623
10.4.1.3 ADU-741
10.4.1.4 ADU-S100
10.5 Agenus Inc
10.5.1 QS-21 Stimulon
10.6 AlphaVax Inc
10.6.1 Alpha Vax’s Technology
10.7 A. MenariniIndustrieFarmaceuticheRiuniteSrl
10.7.1 MEN1112
10.8 Amgen Inc
10.8.1 Vectibix (panitumumab)
10.8.2 Blinatumomab (Blincyto)
10.8.3 Rilotumumab
10.9 Antigen Express Inc
10.9.1 Li-Key Hybrid Vaccines (AE37)
10.10 Argos Therapeutics Inc
10.10.1 AGS-003
10.11 Bavarian Nordic A/S
10.11.1 Prostvac
10.11.2 CV-301
10.11.3 MVA-BN PRP
10.11.4 MVA-BN HER2
10.11.4.1 MVA-BN Brachyury
10.12 Bellicum Pharmaceuticals Inc
10.12.1 BPX-501
10.12.2 BPX-201
10.12.3 BPX-401
10.12.4 BPX-601
10.12.5 BPX-701
10.13 Biogen Idec Inc
10.13.1 Rituxan (Rituximab)
10.13.2 Gazyva (Obinutuzumab)
10.14 Biovest International Inc
10.14.1 BiovaxID
10.15 Bristol-Myers Squibb Company
10.15.1 Erbitux (cetuximab)
10.15.2 OPDIVO (nivolumab)
10.15.3 Yervoy (ipilimumab)
10.16 Cellectis
10.17 Cellerant Therapeutics Inc
10.17.1 CLT-008
10.17.2 CLT-009
10.18 Celldex Therapeutics
10.18.1 Rindopepimut
10.18.2 Glembatumumabvedotin (CDX-011)
10.18.3 Varlilumab (CDX-1127)
10.18.4 CDX-1401
10.18.5 CDX-301
10.19 CEL-SCI Corp.
10.19.1 Multikine
10.20 CureTech Ltd.
10.20.1 Pidilizumab (CT-011)
10.21 Delta-Vir GmbH
10.21.1 Treatment
10.22 Dendreon Corp.
10.22.1 Provenge (Sipuleucel-T)
10.23 DenDrit Biotech USA
10.23.1 MelCancerVac
10.24 DNAtrix Inc
10.24.1 DNX-2401
10.25 Eli Lilly and Co.
10.25.1 Erbitux (Cetuximab)
10.26 EMD Serono Inc
10.27 Etubics Corp.
10.28 Galena Biopharma Inc
10.29 Genentech Inc
10.29.1 Avastin (bevacizumab) for Metastatic Colorectal Cancer
10.29.1.1 Avastin and Interferon Alfa for Metastatic Kidney Cancer
10.29.1.2 Avastin for Metastatic NLCLC
10.29.2 Gazyva (obinutuzumab) for Chronic Lymphocytic Leukemia
10.29.3 Herceptin (trastuzumab) for Breast Cancer
10.29.3.1 Herceptin and Chemotherapy for Gastric Cancer
10.29.4 Kadcyla (ado-trastuzumab emtansine)
10.29.5 Perjeta (pertuzumab)
10.29.6 Rituxan (rituximab)
10.29.7 Genentech’s Cancer Immunotherapy Pipeline Products
10.30 Genmab AS
10.30.1 Ofatumumab
10.31 GlaxoSmithKline
10.31.1 Arzerra (Ofatumumab)
10.31.2 Cervarix
10.32 Gliknik Inc
10.33 GlobeImmune Inc
10.34 Heat Biologics Inc
10.35 Immatics Biotechnologies GmbH
10.36 ImmunoCellular Therapeutics Ltd.
10.37 Immunocore Ltd.
10.37.1 Product Pipeline
10.38 ImmunoFrontier Inc
10.39 ImmunoGen Inc
10.39.1 IMGN853
10.39.2 IMGN529
10.39.3 IMGN289
10.39.4 IMGN779
10.40 Immunomedics Inc
10.41 Immunotope Inc
10.41.1 IMT-1012 Immunotherapeutic Vaccine
10.42 Immunovaccine Inc
10.43 Inovio Pharmaceuticals Inc
10.44 Janssen Biotech Inc
10.44.1 Doxil
10.44.2 Procrit
10.44.3 Zytiga
10.44.4 Imbruvicia
10.45 Juno Therapeutics Inc
10.46 Kite Pharma Inc
10.46.1 Kite Pharma’s Technology
10.46.1.1 eACT (engineered Autologous Cell Therapy)
10.46.1.2 DC-Ad GM-CAIX
10.47 MabVax Therapeutics Holdings Inc
10.48 MedImmune LLC
10.49 Merck & Co., Inc
10.49.1 Gardasil (Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine
10.49.2 Keytruda (Pembrolizumab)
10.50 Merrimack Pharmaceuticals Inc
10.51 Morphotek Inc
10.51.1 Farletuzumab (MORAb-003)
10.51.2 Amatuximab (MORAb-009)
10.51.3 Ontuxizumab (MORAb-004)
10.51.4 MORAb-066
10.52 NewLink Genetics Corp.
10.53 Northwest Biotherapeutics Inc
10.54 NovaRx Corp.
10.55 OncoPep Inc
10.55.1 PVX-410
10.56 Oncothyreon Inc
10.57 OSE Pharma SA
10.58 Oxford BioTherapeutics Ltd.
10.58.1 Technologies
10.58.1.1 OGAP – Cancer Targeting
10.58.1.2 Antibody Development
10.58.1.3 Antibody “arming”
10.58.2 Lead Programs
10.58.2.1 OX001/MEN1112
10.58.2.2 OX002
10.58.2.3 OX003
10.58.2.4 OX004
10.59 Pique Therapeutics
10.60 Polynoma LLC
10.60.1 MAVIS Trial
10.61 Prima BioMed Ltd.
10.62 Progenics Pharmaceuticals Inc
10.62.1 PSMA Targeted Imaging Compound (1404)
10.62.2 PSMA ADC Therapeutic
10.62.3 Small Molecule Therapeutic (1095)
10.62.4 Azedra
10.63 Regen Biopharma Inc
10.63.1 HemaXellerate
10.63.2 dCellVax
10.63.3 Diffron C
10.64 Roche Holdings Inc
10.64.1 Avastin (Bevacizumab)
10.64.2 Gazyva/Gazyvaro (Obinutuzumab; GA101)
10.64.3 Herceptin (Trastuzumab)
10.64.4 Kadcyla (Trastuzumabumemtansinum)
10.64.5 Mabthera (Rituximab)
10.64.6 Perjeta (Pertuzumab)
10.65 Seattle Genetics Inc
10.65.1 Adcetris (Brentuximab vedotin)
10.65.2 Seattle Genetics’ Collaborarator Pipeline
10.66 Sorrento Therapeutics Inc
10.66.1 Sorrento’s Antibody Technologies
10.66.1.1 G-MAB
10.66.1.2 Antibody Drug Conjugates (ADCs)
10.67 Spectrum Pharmaceuticals Inc
10.67.1 Zevalin
10.68 Synthon Pharmaceuticals Inc
10.69 TapImmune Inc
10.70 ThioLogics Ltd.
10.71 Transgene SA
10.72 TVAX Biomedical Inc
10.72.1 TVI-Brain-1
10.72.2 TVI-Kidney-1
10.73 Vaccinogen Inc
10.74 Viventia Biotechnologies Inc
10.75 Wilex AG
10.76 Ziopharm Oncology Inc
11.0 Cancer Immunotherapy Market Participants by Product Segment
12.0 CAR T Therapy
12.1 Challenges Relating to Chimeric Antigen Receptor T Cells in Immunotherapy
12.1.1 Clinical Status of CD19 CAR-T Cells To Date
12.1.2 Clinical and Regulatory Challenges for Development of CAR T Cells
12.1.3 Key Regulatory Challenges Associated with CAR-T Development
12.1.4 Summary of Select CAR-T Products by Juno, Novartis and Kite
12.1.5 Clinical Benefit Versus Toxicity in CD19-Directed ALL Clinical Trials
12.1.6 How to Manage Toxicity of CAR-T Therapy
13.0 Regulations Pertaining to Immunotherapy Regulation in the USA
13.1 Center for Biologics Evaluation and Research (CBER)
13.1.1 Compliance and Surveillance
13.1.2 Extra Resources on Immunotherapeutics from the FDA
13.1.3 Cellular, Tissue and Gene Therapies Advisory Committee
13.1.4 Consumer Affairs Branch (CBER) Contact in FDA
13.1.5 FDA Regulations Pertaining to Immunotherapies
13.1.6 Case Study Ovarian Cancer Immunotherapy Regulations
13.1.6.1 Efficacy
13.1.6.2 Adverse Effects
13.1.7 Trial Design Considerations for Immunotherapy
13.1.8 Development of Immune-Related Response Criteria (irRC) & Clinical Endpoints Specific to Immunotherapies
14.0 Regulations for Immunotherapy in Japan
14.1 PMDA and Immunotherapy
14.1.1 Increasing the Efficiency in Immunotherapy Regulatory Review
14.1.2 Forerunner Review Assignment System
14.1.3 Revised Guidelines for Clinical Evaluation of Anti‐Malignant Tumor Agents
14.1.4 Key Contacts Within the PMDA for Immunotherapeutics
15.0 European Regulation and Immunotherapeutics
15.1 Introduction
15.2 Challenges for Immunotherapy in EMEA
15.2.1 EMA Status on Potency Testing
15.2.1.1 In Vivo Potency Testing
15.2.1.2 In Vitro Potency Testing
15.2.1.3 Viable Cell Count
15.2.1.4 Autologous Cell Based Products
15.2.1.5 Reference Preparation
15.2.1.6 Adjuvant Containing Immunotherapy Products
15.2.2 EMA Status on Identifying hyper, Hypo or non-Responders
15.3 Challenges Relating to Biomarkers in Immunotherapy
15.4 Challenges Relating to Chimeric Antigen Receptor T Cells in Immunotherapy
15.5 Estimating Optimal Cut-Off Parameters
15.6 EU-Approved Immunotherapies in Melanoma
15.7 Key Contacts Within EMA for Immunotherapeutics
16.0 Manufacturing of Immunotherapies
16.1 Introduction
16.2 Generation of CAR-Modified T Cells
16.2.1 What Co-Stimulation and Activity Domain is Optimal to Use?
16.2.2 Optimizing Cell Culture Media
16.2.3 Manufacturing Lentiviral Vectors
16.2.4 Detection of Integrated CAR-Expressing Vectors
16.2.5 Donor Lymphocyte Infusion Procedure
16.2.6 Ex Vivo Costimulation& Expansion of Donor T Cells
16.2.7 Infusion to the Patient
16.3 Manufacturing Devices and Instruments Required for Immunotherapy Production
16.3.1 Leukapheresis
16.3.2 Cell Counters and Analyzer
16.3.3 Cell Seeding, Growth and Propagation
16.4 Good Manufacturing Procedure (GMP) for Immunotherapy
16.5 Case Study Production of Lentivirus Induced Dendritic Cells under GMP Conditions
16.6 Quality Control
16.7 Regulatory Affairs
16.8 Key Challenges in Manufacturing
16.8.1 Electroporation of T-cells
16.8.2 Allogenic CAR T cells
16.8.3 Relapse Rates are Critical
16.8.4 Antigen Negative Relapse
16.8.5 Incorporating Suicide Genes
16.8.16 Automation in Cell Therapy Manufacturing
16.8.17 Autologous Cell Therapy Manufacture Scale Up
17.0 Supply Chain & Logistics
17.1 Introduction
17.2 Case Study: Juno Therapeutics
18.0 Pricing & Cost Analysis
18.1 Introduction
18.2 CAR T Therapy Market Evaluation
19.0 Current Deals Within the CAR T Market
20.0 CAR T Therapy Company Case Studies
20.1 Juno Therapeutics
20.2 Kite Pharma
20.3 Cellectis
Appendix
Immuno-Oncology Highlights and Approvals over the last number of years
Future Directions of Immuno-Oncology
List of Tables
Table 2.1: Types of Immune Cells and their Functions
Table 2.2: FDA-Approved Cancer Immunotherapies
Table 2.3: FDA-Approved Monoclonal Antibodies (MAbs) to Treat Cancer
Table 2.4: Most Frequently Targeted Antigens by MAbs
Table 2.5: FDA-Approved Monoclonal Antibodies
Table 2.6: Cytotoxic Wareheads Used in ADCs
Table 2.7: Targeted Indications for ADCs
Table 2.8: Antibody Drug Conjugates: Developmental Tmeline
Table 2.9: Target Antigens for ADCs in Preclinical and Clinical Development
Table 2.10: Current ADCs Launched, Withdrawn and in Phase I/II/III Trials by Sponsor, Indication, Antigen, Cytotoxin and Linker
Table 2.11: MAb Products and Candidates that Recruit T Cells
Table 2.12: Bispecific MAbs in Clinical Trials Targeting Cancer by Indication and Company
Table 2.13: Bispecific Antibody Technology Platforms
Table 2.14: Side Effects of Some of the Approved Cancer Immunotherapy MAbs
Table 2.15: FDA-Approved Cancer Vaccines
Table 2.16: Cancer Vaccines in Development
Table 2.17: FDA-Approved Cytokines for Cancer Immunotherapy
Table 2.18: Cancer Indications Approved for IFN-alfa
Table 2.19: FDA-Approved Immune Checkpoint Modulators
Table 2.20: Immune Checkpoint Inhibitors in Clinical Development
Table 2.21: Cancer Immunotherapy: Timeline of Progress
Table 3.1: PD-1 Therapies Targeting either the PD-L1/L2 or PD-1 Receptor
Table 3.2: Overview of Clinical Trial Landscape for Top Five Anti-PD-1 and Anti-PD-L1 Drugs
Table 3.3: Nivolumab Efficacy from Expansion Cohorts of Study 003
Table 3.4: Key Clinical Trial Data of Pembrolizumab in Melanoma
Table 3.5: IMpower132 Phase III Data of Tecentriq, (atezolizumab RG7446) in NSCLC Patients
Table 3.6: Phase III IMmotion151 study results of Roche's Tecentriq (atezolizumab) and Avastin (bevacizumab) in Renal Cell Carcinoma
Table 3.7: Phase I Melanoma Data for Tecentriq
Table 3.8: Phase II Data for Pidilizumab in Diffuse Large B Cell Lymphoma (DLBCL)
Table 3.9: Phase II Melanoma Data for Pidilizumab
Table 3.10: An Overview of Anti-PD-1 Development by Company, Drug Candidate, Indication and Clinical Phase
Table 3.11: Clinical Development of CTLA-4, TIM3, and LAG3 Checkpoint Inhibitors by Company, Drug Candidate, Indication and Clinical Trial Stage
Table 3.12: Pivotal Phase III Results for Yervoy in Second-Line Patients with Metastatic Melanoma
Table 3.13: Updated Data from Phase III Clinical Study 024 for Yervoy
Table 3.14: Data from the Failed Phase III Study of Tremelimumab for Melanoma
Table 3.15: An Overview of Clinical Development of Dendritic Cell Therapies by Company, Drug Candidate, Indication and Clinical Phase
Table 3.16: Pivotal Phase III Results for Yervoy in Second-Line Patients with Metastatic Melanoma
Table 3.17: Phase I/Iia Results from Kite Pharma’s CAR-T Therapy
Table 3.18: Cancer Vaccines in Development by Company, Drug Candidate, Indication & Clinical Phase
Table 3.19: Advaxis Phase II Results for Cervical Cancer Patients in India
Table 3.20: Phase II Data for Contego
Table 3.21: Valuable R&D Projects in Cancer Immunotherapy
Table 6.1: Cancer Types Addressed by Immunotherapies by Drug, Trade Name and Company
Table 6.2: Oncology Drugs Losing Patent Protection by 2020 by Product, U.S. Expiry Date and E.U. Expiry Date
Table 7.1: Global Cancer Statistics – Key Facts
Table 7.2: Top Five Most Frequent Cancers, Globally
Table 7.3: Estimated Breast Cancer Cases and Deaths in the U.S. by Age
Table 7.4: Estimated Canadian Breast Cancer Statistics
Table 7.5: Age-Standardized Breast Cancer Incidence Rate per 100,000 Women by Country
Table 7.6: Global Colorectal Cancer Incidence and Mortality Rates by Gender per 100,000 people
Table 7.7: Risk Factors for Colorectal Cancer
Table 7.8: Lung Cancer Incidence and Mortality Rate in Americas by Gender
Table 7.9: Current Therapeutic Options for Lung Cancer
Table 7.10: Estimated Number of New Leukemia Cases in the U.S.
Table 7.11: Estimated Deaths in the U.S. from Leukemia
Table 7.12: Estimated Deaths from HL and NHL in the U.S.
Table 7.13: Estimated Incidence and Deaths for Myeloma in the U.S.
Table 7.14 Global Prostate Cancer Incidence and Mortality Rates by Geography
Table 7.15: Incidence and Mortality Rates of Prostate Cancer in Americas
Table 7.16: Incidence and Mortality Rates for Melanoma in Americas
Table 8.1: Global Market for Oncology Drugs by Geography/Country, Through 2023
Table 8.2: Top Ten Companies in Oncology Sales, Through 2023
Table 8.3: Top Five Oncology Drugs, Through 2023
Table 9.1: Global Cancer Immunotherapy Market, Through 2023
Table 9.2: Global Market for Immunotherapy by Product Class, Through 2023
Table 9.3: Global Market for Immunotherapy Drugs by Cancer Type, Through 2023
Table 9.4: Global Market for Monoclonal Antibodies for Cancer by Type, Through 2023
Table 9.5: Global and U.S. Market for Herceptin, Through 2023
Table 9.6: Global and U.S. Market for Avastin, Through 2023
Table 9.7: Global Market for Cancer Vaccines, Through 2023
Table 9.8: Global Market for Cancer Vaccines by Type, Through 2023
Table 9.9: Projected Market for the Forthcoming DCVax-L and Imfinzi
Table 9.10: Annual Cost of MAbs in the U.S. by Product, Indication and Biomarker
Table 10.1: Ablynx’s Product Pipeline
Table 10.2: Aduro’s Product Pipeline
Table 10.3: Agenus’ Product Pipeline
Table 10.4: AlphaVax Cancer Immunology Product Pipeline
Table 10.5: Amgen’s Product Pipeline
Table 10.6: Antigen Express’ Cancer Therapeutic Pipeline
Table 10.7: Argos’ Cancer Product Pipeline
Table 10.8: Bavarian Nordic’s Product Pipenine
Table 10.9: Bellicum’s Pipeline Product Candidatea
Table 10.10: Biogen’s Oncology Pipeline
Table 10.11: Bristol-Myers Squibb’s Pipeline Products in Cancer Immunotherapy
Table 10.12: Cellectis’ Products in Development
Table 10.13: Cellerant’s Product Pipeline
Table 10.14: Celldex’s Therapeutic Pipeline
Table 10.15: CEL-SCI’s Immunotherapy Products in Development
Table 10.16: EMD Serono’s Product Pipeline
Table 10.17: Etubic’s Product Pipeline
Table 10.18: Galena’s Product Pipeline
Table 10.19: Genentech’s Cancer Immunotherapy Pipeline Products
Table 10.20: Genmab’s Products in Development
Table 10.21: Gliknik’s Product Pipeline
Table 10.22: GlobeImmune’s Product Pipeline
Table 10.23: Heat Biologic’s Product Pipeline
Table 10.24: Immatics Biotechnology’s Product Pipeline
Table 10.25: ImmunoCellular’s Product Pipeline
Table 10.26: Immunomedics’ Late-Stage Antibody-Based Therapies
Table 10.27: Immunovaccine’s Product Pipeline
Table 10.28: Inovio Pharmaceuticals Product Pipeline
Table 10.29: Juno Therapeutics’ Current Pipeline
Table 10.30: Kite Pharma’s Product Pipeline
Table 10.31: MabVax’s Product Pipeline
Table 10.32: MedImmune’s Products in Development
Table 10.33: Merck’s Pipeline of Cancer Immunotherapy Products
Table 10.34: Merrimack’s Product Pipeline
Table 10.35: NewLink Genetics’ Product Pipeline
Table 10.36: Northwest’s Product Pipeline
Table 10.37: NovaRx Clinical Development Pipeline
Table 10.38: Oncothyreon’s Immunotherapy Product Pipeline
Table 10.39: OSE Pharma’s Product Pipeline
Table 10.40: Pique Therapeutics’ Product Pipeline
Table 10.41: Prima BioMed’s Pipeline
Table 10.42: Progenics Pharmaceutical’s Pipeline
Table 10.43: Roche Holding’s Cancer Immunotherapy Product Pipeline
Table 10.44: Seattle Genetics’ Pipeline Products
Table 10.45: Seattle Genetics’ Collaborarator Pipeline
Table 10.46: Synthon Biopharmaceuticals’ Pipeline
Table 10.47: TapImmune’s Product Pipeline
Table 10.48: ThioLogic’s Product Pipeline
Table 10.49: Transgene’s Product Pipeline
Table 10.50: Vaccinogen’s Product Pipeline
Table 10.51: Viventia’s Product Pipeline
Table 10.52: Wilex’s Product Pipeline
Table 10.53: Ziopharm’s Products in Development
Table 11.1: Cancer Immunotherapy Market Participants by Product Segment
Table 12.1: Selected CD19-directed Product Candidates in Clinical Trials by Costimulatory & Binding Domains, Starting Cell Population, Vector and Ablation Technology
Table 12.2: Select CD19-Directed ALL Clinical Trials
Table 12.3: Select Anti-CD22 CAR-T Clinical Projects
Table 13.1: CBER Compliance and Surveillance Activities
Table 13.2: Contacts for the Cellular, Tissue and Gene Therapies Advisory Committee, FDA
Table 14.1: Key Contacts Within PMDA, Japan
Table 15.1: Contact Details for EMA Immunotherapy Experts
Table 16.1: General Technical and Personnel Requirements of a GMP, QC, QA, FDA Regulated Cell Therapy Manufacturing Facility
Table 16.2: Technician/Scientific Requirements for CAR T Manufacturing
Table 16.3: Selection of Apheresis Instruments Currently on the Market
Table 16.4: Selection of Cell Counters and Analyzer Instruments Currently on the Market
Table 16.5: Main Objectives of GMP Manufacturing Immunotherapeutics
Table 16.6: Main Objectives of Quality Control While Manufacturing Immunotherapeutics
Table 16.7: Main Objectives of Regulatory Affairs During Manufacturing Immunotherapeutics
Table 16.8: CAR-T Studies Using mRNA Transfection Electroporation
Table 16.9: Challenges for Autologous Cell Therapy Manufacture
Table 16.10: Current Company/Institutions with Suicide Gene CAR T Projects
Table 16.11: Advantages of Using Automated Cell Therapy Manufacturing
Table 16.12: Main Drivers to Implement Automated Cell Therapy Manufacturing
Table 16.13: Main Benefits of Automated Cell Therapy Manufacturing
Table 16.14: Advantages & Disadvantages of Autologous Cell Therapy Manufacture Scale Up
Table 17.1: Juno Therapeutics Manufacturing Facility Objectives
Table 18.1: Current Juno Therapeutics Trials and CAR T Products
Table 19.1: Current CAR T Business Deals
Table 20.1: Juno Therapeutics Target Biomarker Portfolio
Table 20.2 Juno Therapeutics CAR Technology
Table 20.3 Juno Therapeutics T Cell Receptor (TCR) Technology
Table 20.4 Juno Therapeutics Clinical Pipeline by Target, Product and Trial
Table 20.5: Select CD19-Directed ALL Clinical Trials
Table 20.6: Select Anti-CD22 CAR-T Clinical Projects
Table 20.7 Juno Therapeutics Manufacturing Facility Objectives
Table 20.8 Current Kite Pharma CAR T Clinical Studies and Trials
Table 20.9 Current Kite Pharma TCR Clinical Studies and Trials
List of Figures
Figure 2.1: Components of an Antibody Drug Conjugate (ADC)
Figure 2.2: Mechanism of Action of Antibody Drug Conjugates
Figure 2.3: Ranking of Commonly Used Cytotoxin Wareheads
Figure 4.1: Number of Successful and Unsuccessful Melanoma Drugs
Figure 4.2: Successes and Failures in Lung Cancer Medicine Development
Figure 4.3: Successes and Failures in Brain Cancer Drug Development
Figure 5.1: Ibritumomab Linked to Yttrium Radfionucleotide
Figure 5.2: Kadcyla (Trastuzumab + DMI)
Figure 6.1: Dominance of MAbs and Vaccines in Cancer Clinical Research
Figure 7.1: Global Economic Burden of Cancer
Figure 7.2: Number of Colorectal, Breast and Lung Cancer Cases Diagnosed Globally
Figure 7.3 Percentage of Top Three Cancers Diagnosed Globally
Figure 7.4: Number of Deaths due to Lung, Liver and Stomach Cancers Globally
Figure 7.5: Perce
Related Report
