Market Research Report
DNA Repair Drugs: Focus on PARP Inhibitors, 2016-2026
|Published by||ROOTS ANALYSIS||Product code||358443|
|Published||Content info||284 Pages
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|DNA Repair Drugs: Focus on PARP Inhibitors, 2016-2026|
|Published: May 23, 2016||Content info: 284 Pages||
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.
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 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.
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.
The following companies have been mentioned in the report.
The following organizations have been mentioned in the report.