Medivation/Astellas’ enzalutamide capped off an extraordinary three-year run in advanced castration-resistant prostate cancer therapy, with three successive NMEs each offering a greater survival advantage than the last. That accelerated evolution of new therapies created a complex context for FDA reviews.

Although often overshadowed by the novelty of FDA’s sweeping authority in constructing Risk Evaluation and Mitigation Strategies, examination of agency review documents suggest that the FDA Amendments Act’s other safety innovation, granting FDA the ability to require (i.e., enforce) post-marketing studies, is increasingly important to the approval of NDAs with marginal data on issues of concern.