On the day after Christmas in 2019, Annette Harlow received the final infusion of her lung cancer treatment, only to learn weeks later that the therapy had ceased to be effective. Facing limited options, she was soon informed of a potential new avenue: a clinical trial targeting a mutation in her tumor’s KRAS gene at the University of Texas M.D. Anderson Cancer Center. Enrolling in the Phase 1 trial led by Dr. David Hong, she became one of the earliest patients to receive sotorasib, an experimental drug designed to block effects of the previously undruggable KRAS mutation. More than six years later, Harlow remains optimistic as her cancer is under control.
Dr. Hong, the deputy chair of M.D. Anderson’s Phase 1 program, has dedicated his career to bridging laboratory innovations and patient care, particularly for those with advanced cancer who have exhausted standard treatments. His leadership in trials such as the one for daraxonnazfosib, recently approved by the U.S. Food and Drug Administration (FDA) for pancreatic cancer and shown to nearly double survival rates, underscores his commitment to advancing cancer therapies.
Despite these successes, Dr. Hong expressed concern about the mounting challenges facing clinical trials in the United States. Over recent years, the cost of conducting Phase 1 trials has increased sharply, on average doubling since 2017, with some complex therapies reaching multi-million dollar expenses per patient. These rising costs have prompted pharmaceutical companies to reduce the number of new trials domestically and increasingly conduct studies overseas in countries like Australia and China. This trend limits opportunities for U.S. patients to access cutting-edge treatments and risks shifting biomedical innovation away from the American research landscape.
Experts attribute much of the slowdown to an accumulation of regulatory requirements, which have introduced extensive documentation and lengthy review processes. This regulatory environment frequently duplicates efforts, as trial protocols undergo multiple institutional review boards and FDA assessments, often without clear benefits for patient safety. Researchers recount delays stretching for months due to procedural redundancies, even as the urgent nature of diseases like cancer means that time lost in approvals directly impacts patient survival.
Manufacturing regulations, particularly those governing the production of cell and gene therapies, also pose significant hurdles. Academic clinicians note that FDA standards intended for commercial-scale drug production are ill-suited for early-phase trials requiring only small batches of investigational drugs. Attempts to apply full manufacturing requirements to such trials escalate costs and restrict trial accessibility, despite the FDA’s available, but vague, exemptions.
The cumulative effect has contributed to a decline in drug development efficiency, a phenomenon known as Eroom’s Law, describing how the number of new drug approvals per research dollar has roughly halved every nine years in recent decades, reaching a plateau in the last decade. While advances in artificial intelligence and genomics hold the promise of transforming therapies, stakeholders warn that without regulatory reform, the ability to bring new cures to patients in a timely manner is increasingly compromised. Dr. Hong emphasizes that the primary threat remains the diseases themselves, underscoring the critical need to streamline the clinical trial system to improve patient outcomes.