Poly(adenosine diphosphate
[ADP]–ribose) Polymerases (PARPs) Inhibitors
Successful targeting of DNA Repair Pathways by PARP Inhibitors – Current and Future Potential
[Report Updated: 28-07-2017]


Related Topics: Cancer , Ovarian Cancer

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Introduction

Poly(adenosine diphosphate [ADP]–ribose) polymerases (PARPs) activity is essential for the repair of damaged DNA. The DNA repair pathway is defective/mutated in several cancers (BRCA1, BRCA2 ovarian and breast cancer, etc) and further impairing this pathway by PARP inhibitors in these cancers is the basis of developing DNA repair targeted therapies. In the Last four years three drugs targeting PARPs have been approved for Ovarian Cancer (BRCA mutant) and new clinical data supports further label expansion of this class of drugs in other solid tumors. PARP inhibitors have demonstrated clear patient benefit in germline BRCA (gBRCA), Homologous Recombination (HR)-deficient, and other ovarian cancers. The market opportunity of this class of drug in the approved Ovarian cancer indication itself is large and the best is yet to come from the label expansion in other cancers- Prostate, Breast, Lung, Endometrial, Pancreatic, GlioBlastoma Multiforme (GBM), , etc. as a monotherapy or in combination with other targeted drugs. The innovator companies have pegged the market opportunity of this class of drugs beyond bn which should trigger M&A activity at attractive terms for them. In this report, we highlight the rationale of inhibiting PARP in different cancers and the promising clinical data. Clinical progress of PARP inhibitors as a monotherapy against tumors with existing DNA repair defects, such as BRCA1 and BRCA2 and other mutations, and as a combination therapy when administered with other targeted therapies as well as chemotherapeutics that induce DNA damage.

Table of Contents
for Poly(adenosine diphosphate [ADP]–ribose) Polymerases (PARPs) Inhibitors Successful targeting of DNA Repair Pathways by PARP Inhibitors – Current and Future Potential [Report Updated: 28-07-2017]

  • TABLE OF CONTENTS

    1. Executive Summary 4

    2. Overview of PARP Inhibitors 6

    3. Strategy Used in developing PARP Inhibitors as drugs – Turning Mutations against the Cancer Cells 8

    4. Competitive Landscape – PARP inhibitors-drugs in pipeline 9

    5. Potential of PARP Inhibitors set to Unfold! 11

    6. PARP Inhibitors in Approved Indication- Ovarian Cancer 13

    • Current Treatment options in Ovarian Cancer 14

    • PARP Inhibitors in Ovarian Cancer 14

    • Clinical data and future Label Expansion in Ovarian Cancer 15

    • Ongoing clinical trials in Ovarian cancer 19

    7. Breast Cancer 21

    8. Prostate Cancer 22

    9. Lung Cancer – Non-Small Cell Lung Cancer (NSCLC) 23

    10. Other Cancers 24

    • Pancreatic Cancer 24

    • Endometrial Cancer 25

    • Brain Tumors- GBM 25

    • Gastric Cancer 26

    11. Commercial Outlook 27

    12. M & A Opportunity 29

    13. Key Milestones 31

    14. Appendix I – Ovarian Cancer – Ongoing Clinical Trials 33

    15. Appendix II – Breast Cancer – Ongoing Clinical Trials 40

    16. Appendix III – Prostate Cancer – Ongoing Clinical Trials 45

    17. Appendix IV – Lung Cancer – Ongoing Clinical Trials 47

    18. Appendix V – Other Cancers (Pancreatic, Endometrial, Gastric, GBM, etc.) – Ongoing Clinical Trials 49

List Of Tables
in Poly(adenosine diphosphate [ADP]–ribose) Polymerases (PARPs) Inhibitors Successful targeting of DNA Repair Pathways by PARP Inhibitors – Current and Future Potential [Report Updated: 28-07-2017]

Table 1a PARP Inhibitors: Drugs – Approved and in the Pipeline for Solid Tumors 9-10

Table 1b Comparative in vitro and Other Preclinical Properties of Select PARP Inhibitors 10

Table 2 Comparative Clinical Efficacy and Safety data of Approved PARP inhibitors in Recurrent Advanced Ovarian Cancer 16-18

Table 3 Future Market Potential of PARP inhibitors 27

Table 4 Historical M&A and Licensing Deals for PARP inhibitors 30

Appendix

I Ovarian Cancer – Ongoing Clinical Trials 33-39

II Breast Cancer – Ongoing Clinical Trials 40-44

III Prostate Cancer – Ongoing Clinical Trials 45-46

IV Lung Cancer – Ongoing Clinical Trials 47-48

V Other Cancers (Pancreatic, Endometrial, Gastric, GBM etc.) – Ongoing Clinical Trials 49-56

List Of Figures, Charts and Diagrams
in Poly(adenosine diphosphate [ADP]–ribose) Polymerases (PARPs) Inhibitors Successful targeting of DNA Repair Pathways by PARP Inhibitors – Current and Future Potential [Report Updated: 28-07-2017]

Figure 1A: DNA Repair Pathways 7

Figure 1B: PAPR Inhibitors Drive Synthetic Lethality 7

Figure 2: Rationale for targeting BRCA and Other Mutations by PARP in Solid Tumors 12

Figure 3: Better Therapies for Ovarian Cancer in the Next Five Years 19

Figure 4: Leading sites of Cancer Cases and Deaths – 2017 Estimates: US 28

Figure 5: Leading sites of Cancer Cases and Deaths Estimates: Worldwide 29

Additional Details

Publisher

Publisher Information

Reference

107360 | -

Number of Pages

56

Report Format

PDF

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