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市場調查報告書

DNA修復的PARP抑制劑:2016-2026年

DNA Repair Drugs: Focus on PARP Inhibitors, 2016-2026

出版商 ROOTS ANALYSIS 商品編碼 358443
出版日期 內容資訊 英文 284 Pages
商品交期: 最快1-2個工作天內
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DNA修復的PARP抑制劑:2016-2026年 DNA Repair Drugs: Focus on PARP Inhibitors, 2016-2026
出版日期: 2016年05月23日 內容資訊: 英文 284 Pages
簡介

本報告提供作用於DNA修復的PARP抑制劑的市場調查,DNA損傷、修復系統概要,PARP抑制劑概要與開發的過程,市場環境和開發平台趨勢,主要藥物簡介,主要藥物的患者人口及銷售額規模的變化與預測,競爭藥物類別,未來展望等彙整資料。

第1章 序文

第2章 摘要整理

第3章 DNA損傷、修復系統

  • 本章概要
  • DNA的損傷
  • DNA損傷物質
    • 內因性DNA損傷物質
    • 外因性DNA損傷物質
    • 其他DNA損傷物質
  • DNA損傷應答系
    • DNA修復系統的主要零組件
  • DNA修復系統的各種類型
    • 直接修復
    • 消除修復
    • 間接修復
  • DNA修復的缺點:發病

第4章 PARP (多ADP核糖聚合酵素) 抑制劑

  • 本章概要
  • PARP蛋白質
  • PARP蛋白質的分類
  • PARP蛋白質的解剖學的設計
  • PARP蛋白質的各種用途
  • PARP抑制的治療的可能性
    • 作用機制:合成殺傷力
    • 作用機制:PARP trapping
  • 對遺傳的突然變異、PARP抑制的敏銳度
  • BRCAness和PARP抑制劑的靈敏度
  • 主要的臨床性調查結果
  • DNA的化學合成、放射線增敏劑的PARP抑制劑

第5章 開發的過程

  • 本章概要
  • PARP抑制劑的發現
  • PARP抑制劑的前導的研究
  • PARP抑制劑的初期的失敗
  • 案例研究:Iniparib

第6章 市場環境:PARP抑制劑

  • 本章概要
  • 目前市場環境
  • 開發平台
  • 癌症適應
  • 進化的市場
  • 開發平台:卵巢癌、乳癌作為適應症成為主要目標
  • 開發平台:應對利基患者區分
  • 開發平台:大幅成果推動聯合治療的利用
  • 開發平台:口服給藥仍為偏好的途徑

第7章 藥物簡介

  • 本章概要
  • Olaparib (AstraZeneca)
    • 簡介
    • 開發的過程
    • 給藥計劃、藥價
    • 搭配診斷
    • 銷售額的過程
    • 目前發展情形
    • 臨床試驗
    • 臨床試驗試驗指標
    • 主要的臨床實驗的結果
    • 前臨床的主要調查結果
    • 開發者概要
    • 合作
  • Veliparib (AbbVie)
    • 簡介
    • 目前開發情形
    • 臨床試驗
    • 臨床試驗試驗指標
    • 主要的臨床實驗的結果
    • 前臨床的主要調查結果
    • 開發者概要
    • 合作
  • Niraparib (Tesaro)
    • 簡介
    • 給藥計劃
    • 搭配診斷
    • 專利
    • 目前發展情形
    • 臨床試驗
    • 臨床試驗試驗指標
    • 主要的臨床實驗的結果
    • 前臨床的主要調查結果
    • 開發者概要
    • 合作
  • Talazoparib (Medivation)
    • 簡介
    • 開發的過程
    • 給藥計劃
    • 目前開發情形
    • 臨床試驗
    • 已計劃的研究
    • 臨床試驗試驗指標
    • 主要的臨床實驗的結果
    • 前臨床的主要調查結果
    • 開發者概要
    • 合作
  • Rucaparib (Clovis Oncology)
    • 簡介
    • 開發的過程
    • 給藥計劃
    • 搭配診斷
    • 專利
    • 目前開發情形
    • 臨床試驗
    • 臨床試驗試驗指標
    • 主要的臨床實驗的結果
    • 前臨床的主要調查結果
    • 開發者概要
    • 合作

第8章 市場預測

  • 本章概要
  • 預測手法
  • 整體市場預測
    • Olaparib (Lynparza) (AstraZeneca)
      • 標的患者人口
      • 銷售額預測
    • Veliparib (AbbVie)
      • 標的患者人口
      • 銷售額預測
    • Niraparib (Tesaro)
      • 標的患者人口
      • 銷售額預測
    • Talazoparib (Medivation)
      • 標的患者人口
      • 銷售額預測
    • Rucaparib (Clovis Oncology)
      • 標的患者人口
      • 銷售額預測

第9章 出版物分析

第10章 競爭級

  • 本章概要
  • 直接性方法
    • APE抑制劑 (BER)
    • NER途徑抑制劑 (NER)
    • MGMT抑制劑 (直接修復途徑)
    • DNA蛋白激酶抑制劑 (NHEJ; HRR)
  • 間接的方法
    • 組蛋白去乙醯酶 (HDAC) 抑制劑
    • 週期依賴性激酶 (CDK) 抑制劑
    • CHK1抑制劑
  • 其他的新DNA修復抑制劑
    • SINE XPO1 Antagonist
    • Pyrrolobenzodiazepine Dimers (PBD)
    • RAD51抑制劑
    • DNA結合抗體平台

第11章 總論

第12章 附錄1:圖表

第13章 附錄2:企業、機關清單

圖表

目錄
Product Code: RA10060

DNA is the repository of genetic information in all living cells. Genomic integrity and stability are amongst the key considerations for effective and coordinated biological function. However, DNA is not inert. Cells are continuously exposed to several endogenous and exogenous insults that often cause DNA damage. Despite its role in cellular signalling, ROS, a by-product of mitochondrial respiration, is known to cause severe oxidative DNA damage. Lesions in genomic DNA may also be caused by hydrolysis (deamination, depurination and depyrimidination) and alkylation (6-O-methylguanine) brought about other endogenous insults.Additionally, normal cellular processes, such as replication, are also prone to error. Such erroneous processes often result in the incorporation of incorrect nucleotides leading to formation of lesions in the genome. Exogenous sources of damage may be physical (UV light, ionizing radiations) or chemical (chemotherapeutic drugs, industrial chemicals, cigarette smoke). Overall, it is estimated that every cell experiences up to 105 spontaneous or induced DNA lesions per day.

To detect and correct spontaneous and induced DNA damage, and maintain the integrity and stability of the genome, cells have evolved complex and robust DNA repair mechanisms. The DDR network is a specialized network of proteins and enzymes that is actively engaged in the identification and rectification of lesions and breaks in DNA. Complex organisms have multiple DNA repair pathways, namely the direct repair pathway, excision repair pathways (BER, NER and mismatch repair), and the indirect pathway (HRR and NHEJ). In case one pathway is compromised or rendered dysfunctional, alternate repair pathways are activated to maintain genomic integrity.

Tumor cells that are deficient of a particular repair pathway make optimum use of alternate repair pathways. Such cells up-regulate the expression of certain repair proteins, thereby conferring resistance to therapies that involve DNA damage. Therefore, inhibitors of such compensatory repair pathways have the potential to sensitize cancer cells to DNA damaging agents and associated forms of therapy. The mechanism of action of these drugs relies on the principle of synthetic lethality. PARP inhibitors are an emerging class of drugs that inhibit the BER pathway and lead to the selective elimination of certain types of cancer cells. Normal cells with functional repair pathways remain unaffected by this class of chemotherapeutic drugs.

Currently, only one PARP inhibitor, LynparzaTM (olaparib), is commercially available. Four other PARP inhibitors are being tested in phase III of development for several oncological indications; in addition, molecules are also being developed for non-oncological indications such as smoke inhalation injury and stroke.

Synopsis:

The ‘DNA Repair Drugs: Focus on PARP Inhibitors, 2016-2026' report is an elaborate study of drugs targeting DNA damage and repair systems, particularly, the enzyme PARP. DNA, the repository of genetic information, is susceptible to damage caused by several environmental and synthetic agents. DNA damage leads to the incorporation of defects and aberrations in the genome that often result in functional mutations. When these mutations occur in genes coding for vital proteins and/or enzymes, it leads to the development of genetic diseases. However, our biological system is equipped with a robust repair mechanism capable of correcting damaged DNA sequences. PARP inhibitors and other similar therapeutics are designed to augment the body's innate DNA repair mechanism and aid in the treatment of diseases associated with genetic aberrations. So far, this emerging class of drugs has only been evaluated across a niche population segment. This has led to increased efforts in the development of therapeutics targeting cells that harbor defects in their repair systems. There are several targets, other than PARP, that are also under clinical evaluation.

The PARP inhibitors market consists of a thin but promising pipeline of products targeting various indications. Since its serendipitous discovery, the developmental history of these candidate therapeutics has been full of ups and downs. The recalling of the late stage molecule, iniparib, and the termination of several other candidate therapeutics significantly impacted the growth of this segment of the industry. However, it has picked up pace after the commercialization of LynparzaTM (olaparib), the only marketed PARP inhibitor till date. It is important to highlight the role of companion diagnostics, which have significantly contributed to growth in this segment. These molecular tools enabled therapy developers to accurately identify eligible patient groups. Encouraging clinical results demonstrating prolonged PFS and overall survival rates have also accelerated the progress of this drug class.

One of the key objectives of this study was to review and quantify the opportunities laid by the academia/industry players involved in this space. Considering the success of olaparib and clinical data from other active late stage development programs, we have presented an opinion on the anticipated success of PARP inhibitors. Amongst other elements, the report elaborates upon the following key areas:

  • The current state of the market with respect to key players, developmental status of pipeline products (both clinical/preclinical) and target indications
  • The role of innovative companion diagnostics that have contributed significantly in the development of PARP inhibitors
  • An overview of the competitive landscape, elaborating upon other drug classes that explicitly use the DNA repair system as a therapeutic tool
  • An in-depth analysis of all peer-reviewed literature that is available on the key late stage molecules, published in the past few years
  • Development and sales potential of PARP inhibitors based on target consumer segments, likely adoption rate and expected pricing

The analysis in the report is backed by a deep understanding of key drivers behind the market's growth. With an intent to add comprehensiveness to the market projections, we have provided three market forecast scenarios; the base, optimistic and conservative scenarios represent the likely trends of the future evolution of the market. All actual figures have been sourced and analyzed from publicly available information. The financial figures mentioned in this report are in USD, unless otherwise specified.

Example Highlights:

  • 1. Overall, we have identified 11 unique PARP inhibitors under clinical/preclinical development; of these, eight (73%) are being developed for oncological indications, two (18%) are under development for stroke and one (9%) is being developed for smoke inhalation injury and primary graft dysfunction.
  • 2. Four drugs are in late phase (phase III) of development; veliparib (AbbVie), talazoparib (Medivation), niraparib (Tesaro) and rucaparib (Clovis Oncology).
  • 3. Myriad Genetics and Foundation Medicine have emerged as the major diagnostic developers to actively join hands with PARP inhibitor developers. A companion diagnostic kit called BRACAnalysis CDx®, developed by Myriad Genetics, has been approved to be used with olaparib to detect mutations in the BRCA genes.
  • 4. We anticipate the PARP inhibitors market to grow aggressively at a healthy annual growth rate of 42% between 2016 and 2026. In the longer term, we expect the market to continue to rise steadily with high adoption rates of marketed drugs and approval of new drugs and indications.
  • 5. The overall opportunity will certainly face credible competition from several other classes of DNA repair inhibitors that are currently under development. Some prominent examples include APE inhibitors, nucleotide excision repair (NER) pathway inhibitors, O(6)-methylguanine-DNA methyltransferase (MGMT) inhibitors, DNA-protein kinase (DNA-PK) inhibitors, histone deacetylase (HDAC) inhibitors, cyclin dependent kinase (CDK) inhibitors and checkpoint kinase (CHK1) inhibitors.

Chapter Outlines:

Chapter 2 presents an executive summary of the report. It offers a high level view on where the PARP inhibitors market is headed in the coming few years.

Chapter 3 provides a general introduction to DNA damage and repair. In this section, we have comprehensively discussed DNA damage, providing information on the various types of damages that occur and their causative agents. The chapter also provides information on DNA repair systems and associated biological pathways that are activated during DNA repair. Additionally, it includes a summary of the key clinical findings related to DNA damage and repair that culminated in the development of PARP inhibitors and other similar therapies.

Chapter 4 provides an introduction to PARP inhibitors. It includes information on the classification, anatomical layout and therapeutic potential of PARP inhibitors. The chapter provides a detailed account on the mechanism supporting PARP inhibitors as chemo- and radiosensitizers and their evaluation as combination therapies for oncological indications.

Chapter 5 outlines the evolutionary journey of PARP inhibitors in the current pharmaceutical space. The chapter features a case study on iniparib, the recalled PARP inhibitor; it provides details related to its clinical trial design, key clinical endpoints, key clinical findings, associated side effects and structural features. Additionally, the chapter also talks about other PARP inhibitor programs that were terminated/suspended during clinical development due to various technical reasons.

Chapter 6 provides an overview of the market landscape of PARP inhibitors. This chapter includes information on all the PARP inhibitors that we identified during our research, providing details such as target indications, type of study (combination/monotherapy/maintenance), sub-segment of patients targeted (frontline/pre-treated), phase of development and the active developers engaged in this space.

Chapter 7 contains detailed drug profiles of late stage (phase III) candidate molecules in the PARP inhibitor market. Each drug profile covers information such as mechanism of action, history of development, clinical trial status and assessment of clinical trial endpoints, clinical trial results, manufacturing and a brief overview of the developer company.

Chapter 8 provides a comprehensive view on the market forecast measuring the opportunity over the coming ten years (2016-2026). We have provided the key assumptions, forecast methodology and patient population of the target indications. In addition, we have separately highlighted the contribution of the approved and phase III PARP inhibitors.

Chapter 9 presents a detailed publication analysis of all peer-reviewed, published literature available on the clinical development of late stage PARP inhibitors in the past few years. The chapter presents a robust analysis showcasing the active drugs, evolving trend of publications, focused clinical endpoints and therapeutic areas across the published data.

Chapter 10 provides an insight on the competitive landscape of PARP inhibitors. In this chapter, we have provided a glimpse of the various drug classes that are likely to compete with this emerging class of therapeutics. The chapter outlines the specific mechanisms of competing drugs/therapies, along with a summary of their clinical pipeline. These include drug classes such as APE1 inhibitors, NER inhibitors, MGMT inhibitors, DNA-PK inhibitors, HDAC inhibitors, CDK inhibitors and CHK1 inhibitors.

Chapter 11 summarizes the overall report. In this chapter, we have provided a list of key takeaways and have expressed our independent opinion based on the research and analysis described in previous chapters.

Chapter 12 is an appendix, which provides tabulated data and numbers for all the figures provided in the report.

Chapter 13 is an appendix, which provides the list of companies and organizations mentioned in the report.

Table of Contents

1. PREFACE

  • 1.1. Scope of the Report
  • 1.2. Research Methodology
  • 1.3. Chapter Outlines

2. EXECUTIVE SUMMARY

3. DNA DAMAGE AND REPAIR SYSTEMS

  • 3.1. Chapter Overview
  • 3.2. DNA Damage
  • 3.3. DNA Damaging Agents
    • 3.3.1. Endogenous DNA Damaging Agents
    • 3.3.2. Exogenous DNA Damaging Agents
    • 3.3.3. Other DNA Damaging Agents
  • 3.4. DNA Damage Response System
    • 3.4.1. Key Components of the DNA Repair System
  • 3.5. Types of DNA Repair Systems
    • 3.5.1. Direct Repair
      • 3.5.1.1. Photo Reactivation
      • 3.5.1.2. Alkyl Transferase Mediated Direct DNA Repair
      • 3.5.1.3. AlkB Mediated Direct DNA Repair
      • 3.5.1.4. DNA Ligase Mediated Direct DNA Repair
    • 3.5.2. Excision Repair
      • 3.5.2.1. Base Excision Repair (BER)
        • 3.5.2.1.1. BER Pathway: Key Enzymes
          • 3.5.2.1.1.1. DNA glycosylases: Initiators of the Repair Process
          • 3.5.2.1.1.2. AP Endonucleases
          • 3.5.2.1.1.3. Other Enzymes
        • 3.5.2.1.2. Short-Patch Base Excision Repair
        • 3.5.2.1.3. Long Base Excision Repair
      • 3.5.2.2. Nucleotide Excision Repair (NER)
      • 3.5.2.3. Mismatch Repair (MMR)
    • 3.5.3. Indirect Repair
      • 3.5.3.1. Homologous Recombination Repair (HRR)
      • 3.5.3.2. Non-Homologous End-Joining Repair (NHEJ)
  • 3.6. Defects in DNA Repair: Onset of Disease

4. POLY ADP-RIBOSE POLYMERASE INHIBITORS

  • 4.1. Chapter Overview
  • 4.2. PARP Proteins
  • 4.3. Classification of PARP Proteins
  • 4.4. Anatomical Layout of PARP Proteins
  • 4.5. Applications of PARP Proteins
  • 4.6. Therapeutic Potential of PARP Inhibition
    • 4.6.1. Mechanism of Action: Synthetic Lethality
    • 4.6.2. Mechanism of Action: PARP Trapping
  • 4.7. Genetic Mutations and Susceptibility to PARP Inhibition
  • 4.8. BRCAness and PARP Inhibitor Sensitivity
  • 4.9. Key Clinical Findings
  • 4.10. PARP Inhibitors as Chemosynthesizers and Radiosensitizers

5. HISTORY OF DEVELOPMENT

  • 5.1. Chapter Overview
  • 5.2. Discovery of PARP Inhibitors
  • 5.3. Pioneering Research on PARP Inhibitors
  • 5.4. Early Failure of PARP Inhibitors
  • 5.5. Case Study: Iniparib
    • 5.5.1. Iniparib: Clinical Development Plan
    • 5.5.2. Iniparib: Clinical Trial Endpoints
    • 5.5.3. Iniparib: Key Clinical Findings
    • 5.5.4. Iniparib: Reasons for Failure

6. MARKET LANDSCAPE

  • 6.1. Chapter Overview
  • 6.2. PARP Inhibitors: Current Market Landscape
  • 6.3. PARP Inhibitors: Development Pipeline
  • 6.4. PARP Inhibitors: Oncological Indications Emerge as the Most Targeted Therapeutics Area
  • 6.5. PARP Inhibitors: An Evolving Market
  • 6.6. PARP Inhibitors Pipeline: Ovarian and Breast Cancer are the Primary Target Indications
  • 6.7. PARP Inhibitors Pipeline: Catering to a Unique and Niche Patient Segment
  • 6.8. PARP Inhibitors Pipeline: Significant Results Driving PARP Inhibitors as Combination Therapy
  • 6.9. PARP Inhibitors Pipeline: Oral Administration Continues to be the Preferred Choice

7. DRUG PROFILES

  • 7.1. Chapter Overview
  • 7.2. Olaparib (AstraZeneca)
    • 7.2.1. Introduction
    • 7.2.2. History of Development
    • 7.2.3. Dosage Regimen and Pricing
    • 7.2.4. Companion Diagnostic
    • 7.2.5. Historical Sales
    • 7.2.6. Current Development Status
    • 7.2.7. Clinical Trials
    • 7.2.8. Clinical Trial Endpoints
    • 7.2.9. Key Clinical Trial Results
      • 7.2.9.1. Ovarian Cancer
      • 7.2.9.2. Breast Cancer
      • 7.2.9.3. Gastric Cancer
      • 7.2.9.4. Pancreatic Cancer
      • 7.2.9.5. Prostate Cancer
      • 7.2.9.6. Solid Tumors
    • 7.2.10. Key Preclinical Findings
    • 7.2.11. Developer Overview
    • 7.2.12. Collaborations
  • 7.3. Veliparib (AbbVie)
    • 7.3.1. Introduction
    • 7.3.2. Current Status of Development
    • 7.3.3. Clinical Trials
    • 7.3.4. Clinical Trial Endpoints
    • 7.3.5. Key Clinical Trial Results
      • 7.3.5.1. Lung Cancer
      • 7.3.5.2. Brain Cancer
      • 7.3.5.3. Liver Cancer
      • 7.3.5.4. Pancreatic Cancer
      • 7.3.5.5. Breast Cancer
      • 7.3.5.6. Ovarian Cancer
      • 7.3.5.7. Prostate Cancer
      • 7.3.5.8. Solid Tumors
    • 7.3.6. Key Preclinical Findings
    • 7.3.7. Developer Overview
    • 7.3.8. Collaborations
  • 7.4. Niraparib (Tesaro)
    • 7.4.1. Introduction
    • 7.4.2. Dosage Regimen
    • 7.4.3. Companion Diagnostic
    • 7.4.4. Patents
    • 7.4.5. Current Development Status
    • 7.4.6. Clinical Trials
    • 7.4.7. Clinical Trial Endpoints
    • 7.4.8. Key Clinical Trial Results
      • 7.4.8.1. Solid Tumors
    • 7.4.9. Key Preclinical Findings
    • 7.4.10. Developer Overview
    • 7.4.11. Collaborations
  • 7.5. Talazoparib (Medivation)
    • 7.5.1. Introduction
    • 7.5.2. History of Development
    • 7.5.3. Dosage Regimen
    • 7.5.4. Current Status of Development
    • 7.5.5. Clinical Trials
    • 7.5.6. Planned Studies
    • 7.5.7. Clinical Trial Endpoints
    • 7.5.8. Key Clinical Trial Results
      • 7.5.8.1. Metastatic Breast Cancer
      • 7.5.8.2. Solid Tumors
    • 7.5.9. Key Preclinical Findings
    • 7.5.10. Developer Overview
    • 7.5.11. Collaborations
  • 7.6. Rucaparib (Clovis Oncology)
    • 7.6.1. Introduction
    • 7.6.2. History of Development
    • 7.6.3. Dosage Regimen
    • 7.6.4. Companion Diagnostics
    • 7.6.5. Patents
    • 7.6.6. Current Status of Development
    • 7.6.7. Clinical Trials
    • 7.6.8. Clinical Trial Endpoints
    • 7.6.9. Key Clinical Trial Results
      • 7.6.9.1. Ovarian Cancer
      • 7.6.9.2. Solid Tumors
      • 7.6.9.3. Pancreatic Cancer
    • 7.6.10. Key Preclinical Findings
    • 7.6.11. Developer Overview
    • 7.6.12. Collaborations

8. MARKET FORECAST

  • 8.1. Chapter Overview
  • 8.2. Forecast Methodology
  • 8.3. Overall PARP Inhibitors Market, 2016-2026
    • 8.3.1. Olaparib (Lynparza) (AstraZeneca)
      • 8.3.1.1. Target Patient Population
      • 8.3.1.2. Sales Forecast
    • 8.3.2. Veliparib (AbbVie)
      • 8.3.2.1. Target Patient Population
      • 8.3.2.2. Sales Forecast
    • 8.3.3. Niraparib (Tesaro)
      • 8.3.3.1. Target Patient Population
      • 8.3.3.2. Sales Forecast
    • 8.3.4. Talazoparib (Medivation)
      • 8.3.4.1. Target Patient Population
      • 8.3.4.2. Sales Forecast
    • 8.3.5. Rucaparib (Clovis Oncology)
      • 8.3.5.1. Target Patient Population
      • 8.3.5.2. Sales Forecast

9. PUBLICATION ANALYSIS

  • 9.1. Chapter Overview
  • 9.2. PARP Inhibitors: Overview of Research
  • 9.3. Olaparib Leads the PARP Inhibitors Research Space; Veliparib to Follow
  • 9.4. 2015 Suggests Renewed Interest in This Drug Class
  • 9.5. Combination Therapy Leads the Research Space of PARP Inhibitors
  • 9.6. Phase I Clinical Trial Data is The Most Documented Literature
  • 9.7. Industry and Academia have Both Contributed to the Development of PARP Inhibitors
  • 9.8. Safety: One of the Most Evaluated Clinical Endpoint
  • 9.9. Ovarian Cancer is The Major Focus Area

10. COMPETING CLASSES

  • 10.1. Chapter Overview
  • 10.2. Direct Approach
    • 10.2.1. APE Inhibitors (BER)
    • 10.2.2. NER Pathway Inhibitors (NER)
    • 10.2.3. MGMT Inhibitors (Direct Repair Pathway)
    • 10.2.4. DNA Protein Kinase Inhibitors (NHEJ; HRR)
  • 10.3. Indirect Mechanism
    • 10.3.1. Histone Deacetylase (HDAC) Inhibitors
    • 10.3.2. Cyclin Dependent Kinase (CDK) Inhibitors
    • 10.3.3. CHK1Inhibitors
  • 10.4. Other Novel DNA Repair Inhibitors
    • 10.4.1. SINE XPO1 Antagonist
    • 10.4.2. Pyrrolobenzodiazepine Dimers (PBDs)
    • 10.4.3. RAD51 Inhibitors
    • 10.4.4. DNA Binding Antibody Platform

11. CONCLUSION

  • 11.1. A Robust DNA Damage Response Network Helps Maintain the Integrity and Stability of DNA
  • 11.2. Targeting DNA Repair has Demonstrated Tremendous Anti-Cancer Potential
  • 11.3. PARP Inhibitors: A Leading Class of DNA Repair Inhibitors
  • 11.4. A Thin Therapeutic Pipeline Targeting a Niche Population Across Various Cancer Indications
  • 11.5. Companion Diagnostics Aid in the Identification of the Correct Target Population
  • 11.6. Significant Opportunity Amongst Targeted Inhibitors Highlights A Promising Market Ahead

12. APPENDIX I: TABULATED DATA

13. APPENDIX II: LIST OF COMPANIES AND ORGANIZATIONS

List of Figures

  • Figure 3.1: Types of DNA Damage
  • Figure 3.2: DNA Damage: Types of Causative Agents
  • Figure 3.3: Types of DNA Damage and Repair
  • Figure 3.4: DNA Damage Response System
  • Figure 3.5: Types of DNA Repair Systems
  • Figure 3.6: Base Excision Repair Pathway
  • Figure 3.7: Nucleotide Excision Repair Pathway
  • Figure 3.8: Mismatch Repair Pathway
  • Figure 3.9: Homologous Recombination Repair Pathway
  • Figure 3.10: Non-Homologous End-Joining Repair
  • Figure 3.11: Genetic Disorders Caused due to Defects in DNA Repair Pathways
  • Figure 4.1: PARP Proteins: Mechanism of Action
  • Figure 4.2: Family Tree of PARP Proteins
  • Figure 4.3: Structure of PARP-1 and PARP-2
  • Figure 4.4: Functions of PARP Proteins
  • Figure 4.5: Mutated Tumors Cells and PARP Inhibition
  • Figure 4.6: Mechanism of Action: PARP Trapping
  • Figure 4.7: Systematic Natural DNA Repair vs PARP Inhibition
  • Figure 6.1: PARP Inhibitors Pipeline: Distribution by Phase of Development(PI/II/III/Preclinical)
  • Figure 6.2: PARP Inhibitors Pipeline: Distribution by Target Therapeutic Area
  • Figure 6.3: PARP Inhibitors Pipeline: Distribution by Patient Segment
  • Figure 6.4: PARP Inhibitors Pipeline: Distribution by Type of Study
  • Figure 6.5: PARP Inhibitors Pipeline: Distribution by Route of Administration
  • Figure 7.1: BRACAnalysisCDx Diagnostic Kit: Historical Timeline
  • Figure 7.2: BRACAnalysisCDx Diagnostic Kit: Working Process
  • Figure 7.3: AstraZeneca: Revenues, 2009-2015(USD Billion)
  • Figure 7.4: AbbVie: Revenues, 2010-2015(USD Billion)
  • Figure 7.5: Talazoparib: Unique Features
  • Figure 7.6: Talazoparib: Planned Studies
  • Figure 7.7: Rucaparib: Development Timeline
  • Figure 8.1: Overall PARP Inhibitors Market(USD Million), 2016-2026
  • Figure 8.2: Olaparib Sales Forecast: Base Scenario(USD Million)
  • Figure 8.3: Veliparib Sales Forecast: Base Scenario(USD Million)
  • Figure 8.4: Niraparib Sales Forecast: Base Scenario(USD Million)
  • Figure 8.5: Talazoparib Sales Forecast: Base Scenario(USD Million)
  • Figure 8.6: Rucaparib Sales Forecast: Base Scenario(USD Million)
  • Figure 9.1: PARP Inhibitors Publications: Distribution by Focus Drug
  • Figure 9.2: PARP Inhibitors Publications: Distribution by Year of Publication
  • Figure 9.3: PARP Inhibitors Publications: Distribution by Study Type
  • Figure 9.4: PARP Inhibitors Publications: Distribution by Focus Drug and Study Type
  • Figure 9.5: PARP Inhibitors Publications: Distribution by Phase of Development
  • Figure 9.6: PARP Inhibitors Publications: Distribution by Focus Drug and Phase of Development
  • Figure 9.7: PARP Inhibitors Publications: Distribution by Type of Sponsor
  • Figure 9.8: PARP Inhibitors Publications: Distribution by Focus Drug and Type of Sponsor
  • Figure 9.9: PARP Inhibitors Publications: Distribution by Evaluable Clinical Endpoints
  • Figure 9.10: PARP Inhibitors Publications: Distribution by Focus Drug and Evaluable Clinical Endpoints
  • Figure 9.11: PARP Inhibitors Publications: Distribution by Therapeutic Area
  • Figure 9.12: PARP Inhibitors Publications: Distribution by Drug and Focus Therapeutic Area
  • Figure 10.1: Classification of HDACs
  • Figure 10.2: Cell Cycle Regulation
  • Figure 11.1: PARP Inhibitors And Companion Diagnostics: Collaborations
  • Figure 11.2: Overall PARP Inhibitors Market Summary(USD Million): 2016, 2021, 2026

List of Tables

  • Table 3.1: Components of DNA Repair System
  • Table 3.2: Difference between the HR and NHEJ Pathway
  • Table 4.1: DNA Damaging Agents Used in Cancer Therapy
  • Table 5.1: List of Terminated/Withdrawn PARP Inhibitors
  • Table 5.2: Iniparib: Clinical Trials
  • Table 5.3: Iniparib: Phase III Clinical Trial Endpoints
  • Table 5.4: Iniparib: Phase II Clinical Trial Endpoints-1
  • Table 5.5: Iniparib: Phase II Clinical Trial Endpoints-2
  • Table 6.1: PARP Inhibitors: Clinical/Preclinical Pipeline
  • Table 6.2: PARP Inhibitors: Clinical Development Scenario
  • Table 7.1: Olaparib: Current Status of Development
  • Table 7.2: Olaparib: Industry Sponsored Clinical Trials
  • Table 7.3: Olaparib: Non-Industry Sponsored Clinical Trials
  • Table 7.4: Olaparib: Phase III Clinical Trial Endpoints-1
  • Table 7.5: Olaparib: Phase III Clinical Trial Endpoints-2
  • Table 7.6: Company Overview: AstraZeneca
  • Table 7.7: Veliparib: Current Status of Development
  • Table 7.8: Veliparib: Industry Sponsored Clinical Trials
  • Table 7.9: Veliparib: Non-Industry Sponsored Clinical Trials
  • Table 7.10: Veliparib: Phase III Clinical Trial Endpoints
  • Table 7.11: Company Overview: AbbVie
  • Table 7.12: Niraparib: Patent Portfolio
  • Table 7.13: Niraparib: Current Status of Development
  • Table 7.14: Niraparib: Clinical Trials
  • Table 7.15: Niraparib: Phase III Clinical Trial Endpoints
  • Table 7.16: Niraparib: Phase II Clinical Trial Endpoints
  • Table 7.17: Niraparib: Phase I Clinical Endpoints
  • Table 7.18: Company Overview: Tesaro
  • Table 7.19: Talazoparib: Current Status of Development
  • Table 7.20: Talazoparib: Industry Sponsored Clinical Trials
  • Table 7.21: Talazoparib: Non-Industry Clinical Trials
  • Table 7.22: Talazoparib: Phase II Clinical Trial Endpoints
  • Table 7.23: Talazoparib: Phase I Clinical Trial Endpoints
  • Table 7.24: Company Overview: Medivation
  • Table 7.25: Rucaparib: Current Status of Development
  • Table 7.26: Rucaparib: Clinical Trials
  • Table 7.27: Rucaparib: Phase II Clinical Trial Endpoints
  • Table 7.28: Rucaparib: Phase I Clinical Trial Endpoints
  • Table 7.29: Company Overview: Clovis Oncology
  • Table 8.1: PARP Inhibitors: Market Potential for Candidates
  • Table 8.2: Olaparib: Target Patient Population
  • Table 8.3: Rucaparib: Target Patient Population
  • Table 8.4: Niraparib: Target Patient Population
  • Table 8.5: Veliparib: Target Patient Population
  • Table 8.6: Talazoparib: Target Patient Population
  • Table 9.1: PARP Inhibitors Publications
  • Table 10.1: APE1 Inhibitors Pipeline
  • Table 10.2: NER Inhibitors Pipeline
  • Table 10.3: DNA PK Inhibitors Pipeline
  • Table 10.4: DNA Repair: Effect of Histone Modifications
  • Table 10.5: HDAC Inhibitors Pipeline
  • Table 10.6: CDKs: Functions and Emerging Areas of Research
  • Table 10.7: CDK Inhibitors Pipeline
  • Table 10.8: CHK1 Inhibitors: Clinical Pipeline
  • Table 10.9: Other Novel DNA Repair Inhibitors
  • Table 10.10: Selinexor: Clinical Pipeline
  • Table 12.1: PARP Inhibitors Pipeline: Distribution by Phase of Development(PI/II/III/Preclinical)
  • Table 12.2: PARP Inhibitors Pipeline: Distribution by Target Therapeutic Area
  • Table 12.3: PARP Inhibitors Pipeline: Distribution by Patient Segment
  • Table 12.4: PARP Inhibitors Pipeline: Distribution by Type of Study
  • Table 12.5: PARP Inhibitors Pipeline: Distribution by Route of Administration
  • Table 12.6: AstraZeneca: Revenues, 2009-2015(USD Billion)
  • Table 12.7: AbbVie: Revenues, 2010-2015(USD Billion)
  • Table 12.8: Overall PARP Market: Conservative Scenario(USD Million), 2016-2026
  • Table 12.9: Overall PARP Market: Base Scenario(USD Million), 2016-2026
  • Table 12.10: Overall PARP Market: Optimistic Scenario(USD Million), 2016-2026
  • Table 12.11: Olaparib Sales Forecast: Conservative Scenario(USD Million)
  • Table 12.12: Olaparib Sales Forecast: Base Scenario(USD Million)
  • Table 12.13: Olaparib Sales Forecast: Optimistic Scenario(USD Million)
  • Table 12.14: Veliparib Sales Forecast: Conservative Scenario(USD Million)
  • Table 12.15: Veliparib Sales Forecast: Base Scenario(USD Million)
  • Table 12.16: Veliparib Sales Forecast: Optimistic Scenario(USD Million)
  • Table 12.17: Niraparib Sales Forecast: Conservative Scenario(USD Million)
  • Table 12.18: Niraparib Sales Forecast: Base Scenario(USD Million)
  • Table 12.19: Niraparib Sales Forecast: Optimistic Scenario(USD Million)
  • Table 12.20: Talazoparib Sales Forecast: Conservative Scenario(USD Million)
  • Table 12.21: Talazoparib Sales Forecast: Base Scenario(USD Million)
  • Table 12.22: Talazoparib Sales Forecast: Optimistic Scenario(USD Million)
  • Table 12.23: Rucaparib Sales Forecast: Conservative Scenario(USD Million)
  • Table 12.24: Rucaparib Sales Forecast: Base Scenario(USD Million)
  • Table 12.25: Rucaparib Sales Forecast: Optimistic Scenario(USD Million)
  • Table 12.26: PARP Inhibitors Publications: Distribution by Focus Drug
  • Table 12.27: PARP Inhibitors Publications: Distribution by Year of Publication
  • Table 12.28: PARP Inhibitors Publications: Distribution by Study Type
  • Table 12.29: PARP Inhibitors Publications: Distribution by Focus Drug and Study Type
  • Table 12.30: PARP Inhibitors Publications: Distribution by Phase of Development
  • Table 12.31: PARP Inhibitors Publications: Distribution by Focus Drug and Phase of Development
  • Table 12.32: PARP Inhibitors Publications: Distribution by Type of Sponsor
  • Table 12.33: PARP Inhibitors Publications: Distribution by Focus Drug and Type of Sponsor
  • Table 12.34: PARP Inhibitors Publications: Distribution by Evaluable Clinical Endpoints
  • Table 12.35: PARP Inhibitors Publications: Distribution by Focus Drug and Evaluable Clinical Endpoints
  • Table 12.36: PARP Inhibitors Publications: Distribution by Therapeutic Area
  • Table 12.37: PARP Inhibitors Publications: Distribution by Focus Drug and Focus Therapeutics Area
  • Table 12.38: Overall PARP Inhibitors Market Summary(USD Million): 2016, 2021, 2026

Listed Companies

The following companies have been mentioned in the report.

  • 1. 4SC AG
  • 2. AbbVie
  • 3. Agouron Pharmaceuticals
  • 4. Almac Group
  • 5. Array BioPharma
  • 6. Astellas
  • 7. Astex Pharmaceuticals
  • 8. AstraZeneca
  • 9. BeiGene
  • 10. BioMarin Pharmaceuticals
  • 11. Bristol Myers Squibb
  • 12. BiPar Sciences
  • 13. Celgene
  • 14. Cephalon
  • 15. Checkpoint Therapeutics
  • 16. ChemPartners (Service unit of ShangPharma)
  • 17. Clovis Oncology
  • 18. Cyclacel Pharmaceuticals
  • 19. Cyteir Therapeutics
  • 20. Eisai
  • 21. Eli Lilly
  • 22. Eternity Biosciences
  • 23. Foundation Medicine
  • 24. Genentech
  • 25. GlaxoSmithKline
  • 26. HD Biosciences Corporation
  • 27. Inotek Pharmaceuticals
  • 28. Italfarmaco
  • 29. Jeil Pharmaceutical
  • 30. Jiangsu Hengrui Medicine
  • 31. Johnson & Johnson
  • 32. Karyopharm Therapeutics
  • 33. KuDOS Pharmaceuticals
  • 34. LEAD Therapeutics
  • 35. MedImmune
  • 36. Medivation
  • 37. MEI Pharma
  • 38. Merck
  • 39. Merck KGaA
  • 40. MT Pharma
  • 41. Myriad Genetics
  • 42. NeRX Biosciences
  • 43. Novartis
  • 44. Oncothyreon
  • 45. Onxeo
  • 46. Patrys
  • 47. Pfizer
  • 48. Pharmacyclis
  • 49. PharmaMar
  • 50. Pharmion Corporation
  • 51. Pivot Pharmaceuticals
  • 52. Quintiles
  • 53. Radikal Therapeutics
  • 54. Sanofi
  • 55. Sentinel Oncology
  • 56. Serometrix
  • 57. Sunesis Pharmaceuticals
  • 58. Syndax Pharmaceuticals
  • 59. Tesaro
  • 60. Tiziana Life Sciences
  • 61. Tolero Pharmaceuticals
  • 62. Tracon Pharmaceuticals
  • 63. Vernalis

The following organizations have been mentioned in the report.

  • 1. American Association for Cancer Research
  • 2. ARCAGY/ GINECO GROUP
  • 3. American Society of Clinical Oncology
  • 4. Ascopharm Groupe Novasco
  • 5. Beijing Cancer Hospital
  • 6. Beth Israel Deaconess Medical Center
  • 7. Breast International Group
  • 8. Br.E.A.S.T. -Data Center & Operational Office Institut Jules Bordet
  • 9. Breast Cancer Research Foundation
  • 10. British Columbia Cancer Agency
  • 11. Cambridge University Hospitals NHS Foundation Trust
  • 12. Cancer Research UK
  • 13. Cedars-Sinai Medical Center
  • 14. Christie Hospital NHS Foundation Trust
  • 15. Cooperative Ovarian Cancer Group for Immunotherapy
  • 16. Dana-Farber Cancer Institute
  • 17. European Cancer Congress
  • 18. Eastern Cooperative Oncology Group
  • 19. European Network of Gynaecological Oncology Trial Groups
  • 20. European Organization For Research And Treatment
  • 21. European Society of Gynecological Oncology
  • 22. European Society for Medical Oncology
  • 23. National Health Service
  • 24. European Cancer Observatory
  • 25. FORCE: Facing Our Risk of Cancer Empowered
  • 26. International Federation of Gynecology and Obstetrics
  • 27. Frontier Science & Technology Research Foundation
  • 28. Gynecologic Cancer InterGroup
  • 29. Georgetown University
  • 30. German Breast Group
  • 31. Gynecologic Oncology Group
  • 32. Grupo Espanol de Investigacion del Cancer de Mama
  • 33. Gustave Roussy, Cancer Campus, Grand Paris
  • 34. Hoosier Cancer Research Network
  • 35. Institute of Cancer Research, UK
  • 36. Istituti Ospitalieri di Cremona
  • 37. Istituto Di Ricerche Farmacologiche
  • 38. Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
  • 39. Italian Sarcoma Group
  • 40. Jiangsu Hengrui Medicine
  • 41. Jonsson Comprehensive Cancer Center
  • 42. M.D. Anderson Cancer Center
  • 43. Massachusetts General Hospital
  • 44. Medical School of Newcastle University
  • 45. Memorial Sloan Kettering Cancer Center
  • 46. National Breast Cancer Coalition
  • 47. National Cancer Institute
  • 48. National Crime Information Center
  • 49. New Mexico Cancer Care Alliance
  • 50. Newcastle University
  • 51. The National Institute for Health and Care Excellence
  • 52. Northern Institute of Cancer Research
  • 53. National Institutes of Health
  • 54. National Institutes of Health Clinical Center
  • 55. NSABP Foundation
  • 56. Prostate Cancer Clinical Trials Consortium
  • 57. QuantumLeap Healthcare Collaborative
  • 58. Radiation Therapy Oncology Group
  • 59. Royal Marsden NHS Foundation Trust
  • 60. Samsung Medical Centre
  • 61. SARC
  • 62. Sheba Medical Center
  • 63. Sidney Kimmel Comprehensive Cancer Center
  • 64. SOLTI Breast Cancer Research Group
  • 65. Spanish Lung Cancer Group
  • 66. St. Jude Children's Research Hospital
  • 67. Stanford University
  • 68. Swedish Medical Center
  • 69. The Netherlands Cancer Institute
  • 70. Third Military Medical University
  • 71. Translational Research in Oncology
  • 72. UNC Lineberger Comprehensive Cancer
  • 73. UNICANCER
  • 74. University College, London
  • 75. University Health Network
  • 76. University of California, San Francisco
  • 77. University of Colorado
  • 78. University of Michigan Cancer Center
  • 79. University of Sheffield
  • 80. University of Toronto
  • 81. University of Washington
  • 82. US Department of Health and Human Services
  • 83. US Department of Labor
  • 84. US Department of Treasury
  • 85. US Oncology Research
  • 86. Vanderbilt-Ingram Cancer Center
  • 87. Vejle Hospital
  • 88. Velindre NHS Trust
  • 89. Yale University
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