From the Valley of Death to the Crossroads of Opportunity

Abstract

A series of recent US Food and Drug Administration (FDA) approvals (such as Sarepta’s Exondys 51, Merck’s Keytruda, and Portola’s Bevyxxa) has generated significant interest within the drug development ecosystem. Facilitated regulatory pathways aimed toward expediting medicines to patients suffering from serious and life-threatening conditions are a good thing, even if it raises curiosity and introduces some degree of uncertainty. Over the last 20 years, two key words in drug development have been speed and innovation. Going forward, the patient voice, data quality, and evidence generation must be added to that list. There is a raging debate over the level of evidence expected to first introduce a treatment to patients. Some argue for less data followed by postapproval follow-up, others for more adaptive clinical trial designs and end-point modification driven by patient-focused drug development and use of real-world evidence. The transition in the regulatory framework is happening in front of our eyes. How are these shifts in regulatory science interpreted within the context of 21st-century drug development—and how can these learnings help advance patient care while placing into context the expected uncertainty we find in benefit-risk data?