Regulating By Example: FDA’s Sampling Of Accelerated Approval Endpoints

Prolonged suppression of HIV viral load in plasma has been shown to reduce the morbidity and mortality associated with HIV disease and has been the basis for traditional approval. Shorter-term suppression of viral load has been used in the past as a surrogate to support accelerated approval because it was considered reasonably likely to predict an effect on morbidity or mortality. Data now demonstrate that short-term suppression of viral load may support full approval, in some circumstances.

Clearance of bacteria from the bloodstream as evidenced by a laboratory measurement of bacteria in the blood has been considered reasonably likely to predict the clinical resolution of infection.

Outcomes of six-month follow-up treatment (i.e., sputum culture status and infection relapse rate) have been considered reasonably likely to predict the resolution of pulmonary tuberculosis.

Decrease in iron stores for patients with iron overload caused by thalassemia has been considered reasonably likely to predict a decrease in transfusion-related adverse events caused by iron overload in the body.

Radiographic evidence of tumor shrinkage (response rate) in certain cancer types has been considered reasonably likely to predict an improvement in overall survival.

A treatment for multiple sclerosis was approved based on a large therapeutic effect on relapse rate through approximately 13 months of treatment, but where there was uncertainty about the durability of the observed effect. Under accelerated approval, the sponsor was required to continue the existing trials into the post-marketing period to confirm durability of the observed effect at two years.

A treatment for preterm labor was approved based on a demonstration of delay in delivery. Under accelerated approval, the sponsor was required to conduct post-marketing studies to demonstrate improved long-term postnatal outcomes.

Source: FDA final guidance, “Expedited Programs for Serious Conditions – Drugs and Biologics”

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