Reply to Stowasser et al. : Assessing How Patients Feel, Function, and Survive in Idiopathic Pulmonary Fibrosis: The Best Is the Enemy of the Good
Year: 2024
Type: letter
Abstract: development in this field.However, as the only currently accepted surrogate endpoint, FVC poses significant challenges for drug developers and the pulmonary fibrosis community, as new drug candidates now must demonstrate their effects on FVC decline on top of standard of care; there is only limited room for improvement left given the physiologic trajectory of lung function over a defined period of evaluation.We agree that changes in FVC over 12 weeks in small trials (3) may not serve as a surrogate for overall survival; however, it may be premature to conclude that short-term changes in FVC in adequately designed studies cannot provide proof of concept.Ongoing trials with bexotegrast (also known as PLN-74809) and nerandomilast (also known as BI 1015550) may tell us about the appropriateness of 12-week FVC measurements as proof of concept (4, 5), and we should be open to learning from these newly emerging data and their correlation with data from ongoing late-stage trials with changes in FVC at 52 weeks.The efforts by the symposium participants (including patients and regulators) to propose other potential endpoints in IPF clinical trials are noble; we should all be focusing on meaningfully improving the lives of patients with IPF, not merely showing a statistically significant effect on a parameter that patients do not often feel.Are there better endpoints than FVC for clinical trials in IPF? Undoubtedly!Do we know all the pros and cons of using these novel endpoints?Absolutely not, but we will eventually with the collective efforts of all stakeholders.We cannot let "the best" become the enemy of "the good."Focusing on having all the information about an endpoint's true meaning before adopting it in clinical trials (and even clinical practice) will delay the development of better therapeutic options for patients with IPF.Postmarketing surveillance and realworld data may be needed in addition to those from robust and rigorous trials to provide the assurances physicians, patients, and regulators seek that a drug improves the lives of patients; this cannot happen in the context of a clinical development program alone.A good-faith joint effort involving all stakeholders (including drug developers) is needed to overcome our collective challenges and not hinder successful drug development and progress.The symposium summarized by Raghu and colleagues (1) is a good and urgently needed starting point.Overcoming these hurdles will require courage, innovation, pragmatism, and inclusive discussion with all key stakeholders.Only then will we truly achieve results that affect how patients feel, function, and survive.
Institutions: University of Washington, Weill Cornell Medicine
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4399204344