Novel Targeted Therapies: A Challenge for Drug Development

2003 ◽  
Vol 5 ◽  
pp. S4
Author(s):  
Chandra P. Belani
Keyword(s):  
Drug Development ◽  
Targeted Therapies

scholarly journals Cancer drug development: The missing links

2019 ◽  
Vol 244 (8) ◽  
pp. 663-689 ◽  
Author(s):  
Ajaikumar B Kunnumakkara ◽  
Devivasha Bordoloi ◽  
Bethsebie Lalduhsaki Sailo ◽  
Nand Kishor Roy ◽  
Krishan Kumar Thakur ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Drug Development ◽  
Targeted Therapies ◽  
Science And Technology ◽  
Development Cost ◽  
Phase I Clinical Trials ◽  
Drug Benefits ◽  
Number Of Patients ◽  
Pharmaceutical Industries

Although better science and technology has been linked with better health care, however, reality is much different. Although America and most of Europe are equipped with most advanced science and technology, paradoxically cancer incidence is highest in the world. This indicates that science and technology alone is not sufficient in treating diseases like cancer. It is also now well recognized that more than 95% of the drugs/compounds that kill either cancer cells in culture or regress the tumors in animals, fail in phase I clinical trials in humans, indicating that most pre-clinical models of cancer are inadequate. In addition, most of the anticancer drugs that are approved by the regulatory agencies such as FDA either has no effect on the overall survival of the cancer patient or may provide an increase in few months in overall survival. This is despite the fact that most targeted therapies that are currently available are highly expensive; thus suggesting the lack of affordability. This review is meant to focus on some of these problems in detail and then provide potential solutions since most cancers are caused by multiple genes, and thus multi-targeted therapies are needed such as natural products which are inexpensive, safe and have been used for thousands of years for both prevention and treatment of cancer. Impact statement The success rate for cancer drugs which enter into phase 1 clinical trials is utterly less. Why the vast majority of drugs fail is not understood but suggests that pre-clinical studies are not adequate for human diseases. In 1975, as per the Tufts Center for the Study of Drug Development, pharmaceutical industries expended 100 million dollars for research and development of the average FDA approved drug. By 2005, this figure had more than quadrupled, to $1.3 billion. In order to recover their high and risky investment cost, pharmaceutical companies charge more for their products. However, there exists no correlation between drug development cost and actual sale of the drug. This high drug development cost could be due to the reason that all patients might not respond to the drug. Hence, a given drug has to be tested in large number of patients to show drug benefits and obtain significant results.

scholarly journals The Michael J. Fox Foundation’s Strategies for Accelerating Translation of LRRK2 into Therapies for Parkinson Disease

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1878
Author(s):  
Shalini Padmanabhan ◽  
Brian K. Fiske ◽  
Marco A.S. Baptista
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Parkinson Disease ◽  
Targeted Therapies ◽  
Kinase Inhibitors ◽  
Critical Research ◽  
Development Activity ◽  
Potential Safety ◽  
Lrrk2 Kinase ◽  
Holistic Description

Since 2005, The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has invested significant funding and non-funding effort to accelerate research and drug development activity around the Parkinson disease (PD)-associated protein LRRK2. MJFF has spearheaded multiple public/private pre-competitive collaborations that have contributed to our understanding of LRRK2 function; de-risked potential safety questions around the therapeutic use of LRRK2 kinase inhibitors; and generated critical research tools, biosamples, and data for the field. Several LRRK2-targeted therapies are now in human testing due to the hard work of so many in the PD community. In this perspective, we present a holistic description and model of how our Foundation’s support targeted important barriers to LRRK2 research and helped move the field into clinical trials.

Cardiotoxicity of ErbB2-targeted therapies and its impact on drug development, a spotlight on trastuzumab

2017 ◽  
Vol 13 (7) ◽  
pp. 755-766 ◽  
Author(s):  
Milos Dokmanovic ◽  
Kathryn E. King ◽  
Nishant Mohan ◽  
Yukinori Endo ◽  
Wen Jin Wu
Keyword(s):  
Drug Development ◽  
Targeted Therapies

scholarly journals The FDA Oncology Center of Excellence and precision medicine

2017 ◽  
Vol 243 (3) ◽  
pp. 308-312 ◽  
Author(s):  
Kirsten B Goldberg ◽  
Gideon M Blumenthal ◽  
Amy E McKee ◽  
Richard Pazdur
Keyword(s):  
Drug Development ◽  
Precision Medicine ◽  
Targeted Therapies ◽  
Treatment Options ◽  
Regulatory Science ◽  
Cancer Drug ◽  
Center Of Excellence ◽  
Life Threatening ◽  
Oncology Center ◽  
The U.S

In January 2017, the U.S. Food and Drug Administration (FDA) formally established the Oncology Center of Excellence (OCE) to streamline the development of cancer therapies by uniting experts from FDA product centers to conduct expedited review of drugs, biologics, and devices. In May 2017, the FDA approved a cancer treatment based on a biomarker, without regard to the tumor’s site, by granting accelerated approval to pembrolizumab for patients with solid tumors that have the microsatellite instability-high or mismatch repair deficient biomarker. We describe here the OCE’s role in this first site-agnostic approval and OCE programs for further advancement of oncology-related regulatory science and policy. In addition, the FDA’s four expedited review programs that enable transformative therapies to reach patients with life-threatening malignancies earlier in the development process are key to the continued rapid development of safe and effective therapies for patients with few or no other treatment options. These changes at FDA are taking place in the context of recent progress in the understanding of the genetic and immunologic foundations of cancer, resulting in the development of targeted therapies and immunotherapies. The traditional system of phased clinical trials has evolved as early trials of breakthrough therapies use expansion cohorts in a process known as seamless drug development. Increasingly, FDA approvals of targeted therapies are likely to have contemporaneous approvals of companion diagnostics to identify patients whose cancers harbor actionable abnormalities. Impact statement This publication describes the U.S. Food and Drug Administration’s (FDA) first site-agnostic oncology drug approval, a landmark event in the history of cancer drug development. The role of the FDA’s newly established Oncology Center of Excellence (OCE) in this approval is described, as are several OCE programs to advance excellence in regulatory science in the era of precision medicine. Also provided is an overview of FDA’s expedited drug review programs, which are important to the continued acceleration of therapeutics development for patients with life-threatening diseases and few or no other treatment options.

scholarly journals Evidence-Based Laboratory Medicine in Oncology Drug Development: From Biomarkers to Diagnostics

2013 ◽  
Vol 59 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Vijay Modur ◽  
Eric Hailman ◽  
JC Barrett
Keyword(s):  
Drug Development ◽  
Targeted Therapies ◽  
Diagnostic Tests ◽  
Laboratory Medicine ◽  
Organ Injury ◽  
Cancer Drug ◽  
Early Tumor Response ◽  
Fit For Purpose ◽  
Early Tumor ◽  
Assessment Strategies

BACKGROUND The promise of targeted therapies in molecularly defined subsets of cancer has led to a transformation of the process of drug development in oncology. To target cancer successfully and precisely requires high-quality translational data. Such data can be generated by the use of biomarkers that answer key questions in drug development. CONTENT Translational data for aiding in decision-making and driving cancer drug development can be generated by systematic assessments with biomarkers. Types of biomarkers that support decisions include: pharmacodynamic assessments for selecting the best compound or dosage; assessment of early tumor response with tissue biomarkers and imaging, mutation, and other assessment strategies for patient selection; and the use of markers of organ injury to detect toxicity and improve safety. Tactics used to generate biomarker data include fit-for-purpose assay validation and real-time biomarker assessments. Successfully translated and clinically informative biomarkers can mature into novel companion diagnostic tests that expand the practice of laboratory medicine. SUMMARY Systematic biomarker assessments are a key component of the clinical development of targeted therapies for cancer. The success of these biomarker assessments requires applying basic principles of laboratory medicine to generate the data required to make informed decisions. Successful biomarkers can transition into diagnostic tests that expand the laboratory medicine armamentarium.

Clinical trial risk reduction in non-small cell lung cancer though the use of biomarkers and receptor-targeted therapies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8040-8040
Author(s):  
Adam Falconi ◽  
Gilberto Lopes ◽  
Jayson L. Parker
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Drug Development ◽  
Phase I ◽  
Success Rate ◽  
Targeted Therapies ◽  
Phase Iii ◽  
Clinical Testing ◽  
Phase Ii Trials ◽  
Phase Iii Trials

8040 Background: We analyzed the risk of clinical trial failure duringnon-small cell lung cancer (NSCLC) drug development between 1998 and 2012. Methods: NSCLC drug development was investigated using trial disclosures from publically available resources. Compounds were excluded from the analysis if they began phase I clinical testing before 1998 and if they did not use treatment relevant endpoints. Analysis was conducted in regards to treatment indication, compound classification and mechanism of action. Costs of clinical drug development for advanced NSCLC were calculated using industry data and assumptions, a 9% yearly discount rate and assuming a clinical trial length of 2.5 years for phase I trials, 4 years for phase II trials, 5 years for phase III trials and an average of 5 phase I trials, 7 phase II trials, and 4 phase III trials per approved drug. All funding costs are in US dollars (USD). Results: 2,407 clinical trials met search criteria. 676 trials and 199 unique compounds met our inclusion criteria. The likelihood, or cumulative clinical trial success rate, that a new drug would pass all phases of clinical testing and be approved was found to be 11%, which is less than the expected industry aggregate rates (16.5%). The success of phase III trials was found to be the biggest obstacle for drug approval with a success rate of only 28%. Biomarker-guided targeted therapies (with a success rate of 62%) and receptor targeted therapies (with a success rate of 31%) were found to have the highest likelihood of success in clinical trials. The risk-adjusted cost for NSCLC clinical drug development was calculated to be 1.89 billion US dollars. Use of biomarkers decreased drug development cost by 26% to 1.4 billion US dollars. Potential savings may be even higher if fewer clinical trials are required for successful development. Conclusions: Physicians that enroll patients in NSCLC trials should prioritize their participation in clinical trial programs that involve either a biomarker or receptor targeted therapy, which appear to carry the best chances for a successful treatment response. Given the high adjusted cost of clinical testing alone in NSCLC, efforts to mitigate the risk of trial failure need to explore these factors more fully.

Optimal Dosing for Targeted Therapies in Oncology: Drug Development Cases Leading by Example

2015 ◽  
Vol 22 (6) ◽  
pp. 1318-1324 ◽  
Author(s):  
Jeffrey R. Sachs ◽  
Kapil Mayawala ◽  
Satvik Gadamsetty ◽  
Soonmo Peter Kang ◽  
Dinesh P. de Alwis
Keyword(s):  
Drug Development ◽  
Targeted Therapies ◽  
Oncology Drug ◽  
Optimal Dosing ◽  
Oncology Drug Development
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