Poly(adenosine diphosphate [ADP]–ribose) Polymerases (PARPs) Inhibitors

Successful targeting of DNA Repair Pathways by PARP Inhibitors – Current and Future Potential

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 $5bn 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 chemo-therapeutics that induce DNA damage.

Recent Hot Deals (July 2017) in the PARP space –

AstraZeneca and Merck inked $8.5bn PARP - Olaparib (LYNPARZA in the US) and MEK inhibitor Deal

TESARO granted Takeda Pharma rights to Niraparib (ZEJULA in the US) in Japan for all types of cancer

PARP Inhibitors – What You Will Learn

  • Could PARP inhibitors be effective for BRCA-associated breast, pancreatic, prostate cancers and other cancers?
  • Will PARP inhibitors be effective in all HR deficient tumors?
  • Can PARP inhibitors be successful with inhibitors of other signaling pathways to create clinical synthetic lethality?
  • Should PARP inhibitors be used alone or in combination with other drugs to treat newly diagnosed cancers in BRCA mutation carriers?
  • Are some PARP inhibitors more effective or less toxic than others?
  • Should women diagnosed with ovarian cancer take PARP inhibitors after chemotherapy as "maintenance therapy" to reduce the chances of relapse?
  • Whether PARP inhibitors might play a role in cancer prevention-i.e., as a means of avoiding prophylactic surgeries in BRCA mutation carriers?

Research Methodology

Research methodology is based on in-depth research and market study, scientific journals or technical literature, industry publications, company reports and published information, and statistical data from government agencies and other therapy foundation or associations.  Forecasts and projections of market size and future market activity are derived using standard modelling and statistical techniques.

Author Bio

Subita Srimal

ProGrow Pharma (PGP) Partners caters the full spectrum of services to Pharma companies (Pharma/ Biotech, Generic, CRAMS, CROs, Start-ups) and its Investors (Private Equity, Fund Managers, HNI).  With decades of experience in strategic advisory, regulatory aspects, technical publications, understanding complex drugs, identifying market potential and all related services, the team is widely approached by pharmaceutical companies and experts.  Our team can support you from defining strategic programmes to providing expert guidance for tactical operations to transform your operational or market based challenges into growth aligned opportunities.

  1. Executive Summary
  2. Overview of PARP Inhibitors
  3. Strategy Used in developing PARP Inhibitors as drugs – Turning Mutations against the Cancer Cells
  4. Competitive Landscape – PARP inhibitors-drugs in pipeline
  5. Potential of PARP Inhibitors set to Unfold!
  6. PARP Inhibitors in Approved Indication- Ovarian Cancer
    • Current Treatment options in Ovarian Cancer
    • PARP Inhibitors in Ovarian Cancer
    • Clinical data and future Label Expansion in Ovarian Cancer
    • Ongoing clinical trials in Ovarian cancer
  7. Breast Cancer
  8. Prostate Cancer
  9. Lung Cancer – Non-Small Cell Lung Cancer (NSCLC)
  10. Other Cancers
    • Pancreatic Cancer
    • Endometrial Cancer
    • Brain Tumors- GBM
    • Gastric Cancer
  11. Commercial Outlook
  12. M & A Opportunity
  13. Key Milestones
  14. Appendix I – Ovarian Cancer – Ongoing Clinical Trials
  15. Appendix II – Breast Cancer – Ongoing Clinical Trials
  16. Appendix III – Prostate Cancer – Ongoing Clinical Trials
  17. Appendix IV – Lung Cancer – Ongoing Clinical Trials
  18. Appendix V – Other Cancers (Pancreatic, Endometrial, Gastric, GBM, etc.) – Ongoing Clinical Trials
  • AstraZeneca
  • Clovis Oncology
  • Eli Lilly
  • Bristol-Myers Squib
  • TESARO
  • Zai Lab China
  • Pfizer
  • AbbVie
  • BeiGene
  • Checkpoint Therap.
  • Merck
  • Jiangsu HengRui
  • Oncology Venture / 2X Oncology
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