Cancer Drug Development: Views From Industry
Kiran Patel, MD, Janssen Research & Development, LLC, Raritan, New Jersey, USA
Authored by Jessica Hawley, MD, Columbia University Medical Center, New York, New York, USA
Cancer rates are increasing rapidly. In the past ten years there has been a 28% increase in global cancer cases. U.S. cancer death estimates are projected to nearly double by 2035. Fortunately, drug development has become a highly regulated process founded on statistical evidence and precise science, as compared to the merely empirical evidence of anecdotal experience which directed treatments in the past. However, drug development remains a long and complex process, beginning with an idea, leading to discovery, then to clinical trial development, and finally to FDA registration – with several steps in between. At each step of development, there is a 90% chance the drug will not make it to the next step. In fact, for every 5-10,000 compounds in development, only one will yield a new FDA approved agent. The entire process of drug development can take 10-15 years, which represents a major obstacle to cancer care, especially when considering the staggering projected increase in cancer rates mentioned above.
Dr. Patel discussed particular obstacles to small molecule inhibitor and antibody drug development, highlighting particular challenges from both the basic-science bench side (toxicology, biology, pharmacology) and from the clinical development standpoint. The cost of R&D per drug is $5.8 billion, which includes the cost of the failed compounds. This is astounding. However, encouragingly, the timeline gap is beginning to close. This is exemplified by the following examples: Gleevec’s development took 41 years; herceptin took 13, BRAF inhibition took 7, and crizotinib took only 3.
Dr. Patel went on to discuss the impact these breakthroughs have had on patient care, including decreased cancer deaths overall. He highlighted some of the FDA mechanisms in place that have helped accelerate drug approval when promising clinical results are realized. And finally, he discussed some of the newer agents and types of therapies stemming from antibodies coming down the pipeline (tumor-specific Ab, ICB, radioimmuntherapy, CAR T cells, ADCs, and bispecifics), as well as Janssen’s recent focus on targeting and understanding patients who are at high-risk of developing cancer and how best to target premalignancy risk factors earlier on.
Authored by Devika Rao, MD, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA
Having a senior member of the industry, Dr. Kiran Patel, speak of his experiences in navigating the transition from academic training onto uncharted paths was extremely interesting. It served as an apt reminder that no one size ever fits all, especially when navigating the complex winding path of new drug development. The process of drug approval was detailed, from the initial conception of the idea, the timeline to preclinical data generation, and eventual transition to human trials. Successes gained in melanoma and lung cancer served as the backdrop to this talk. The room was reminded of the drug developmental pyramid wherein five to ten thousand products would be tested before one single drug could be approved, which explained the growing economic burden of new drug development. Nuances of small molecule and antibody development were further discussed, highlighting the need for close collaboration between researchers in the clinic and on the bench. Changes in the FDA and the new category of expedited programs have helped speed the process of bringing new and more effective drugs to the bedside more rapidly than ever before. However there remain multiple unanswered questions on novel approaches to tumors as we gain more understanding of their biology, and there is immense scope for career advancement in this field.