Accelerated orphan drug approval: surrogate endpoints

Today, orphan drug development is confronted with significant challenges represented by the considerable complexity, diversity of clinical manifestations, and competition in study recruitment. Thus, surrogate endpoints adoption plays a crucial role in rare disease trials by minimizing costs, the number of subjects, and study duration. Surrogate endpoints, to substitute for a direct measure of how patients feel, function, or survive, must be biomarkers that directly correlate with disease clinical manifestations and predict the impact of study drug on the long-term disease progression. Validation of surrogate endpoints for accuracy and sensitivity is essential to maximize its benefit and utility. These validation criteria include reliability, reproducibility, keenness, and a direct reflection of patient feeling, function, or survival upon treatment. On the other hand, the selection of surrogate endpoints may be pretty complex, and making mistakes may lead to inaccurate estimates of the clinical benefit. Finally, surrogate endpoints contribute to a composite endpoint when studying drug benefits patients in multiple ways, and not all the measured components are detected in each patient. Furthermore, a composite endpoint comprised of multiple surrogate endpoints could improve statistical efficiency. Selection and qualification of biomarkers for surrogate endpoints and accelerated market approval is often a complex process that requires experience and method. Today, we contributed to developing orphan drugs for many rare diseases, including Neurological Diseases, Lysosomal Storage Diseases, Metabolic Conditions, Immune Disorders, and Cancers. In conclusion, surrogate endpoints play an essential role in orphan drug development, benefiting patients and the healthcare system.