Eli Lilly Gains Traditional FDA Approval for Selpercatinib in RET-Mutant Medullary Thyroid Cancer

The conversion of selpercatinib (Retevmo, Eli Lilly and Company) from accelerated to traditional approval on September 27, 2024 closes a post-market commitment loop that regulatory affairs teams have been tracking since the drug's original 2020 accelerated approval for RET-mutant medullary thyroid cancer (MTC). The decision now covers adult and pediatric patients aged 2 years and older with advanced or metastatic disease requiring systemic therapy, contingent on confirmation via an FDA-approved companion diagnostic.

Confirmatory evidence came from LIBRETTO-531 (NCT04211337), a randomized, multicenter, open-label study in adults and adolescents. Patients were randomized 2:1 to selpercatinib 160 mg twice daily or physicians' choice of cabozantinib or vandetanib. The primary endpoint, progression-free survival assessed by blinded independent review per RECIST v1.1, was not reached in the selpercatinib arm versus 16.8 months in the comparator arm (HR 0.280; 95% CI: 0.165, 0.475; p<0.0001). A pre-specified patient-reported outcomes analysis further supported the benefit-risk profile, with selpercatinib patients reporting less time with severe side-effect burden.

For regulatory affairs leads managing accelerated approval portfolios, the LIBRETTO-531 dataset is a functional template: a randomized, active-controlled design with a time-to-event primary endpoint and a pre-specified PRO analysis satisfying FDA's confirmatory evidence standard. The application also used FDA's voluntary Assessment Aid submission, which the agency has increasingly encouraged to streamline review efficiency under its expedited programs framework.

The pediatric extension carries its own regulatory sequence worth noting. Accelerated approval for patients aged 2 to under 12 years was granted separately on May 29, 2024, only months before the traditional approval consolidated both cohorts. Dosing for this younger group is body-surface-area-based, distinct from the weight-based regimen for patients 12 and older, a CMC and labeling consideration for any site involved in commercial supply or post-approval change management.

The most common adverse reactions at or above 25% incidence were hypertension, edema, dry mouth, fatigue, and diarrhea. Grade 3 or 4 laboratory abnormalities occurring in 5% or more of patients included decreased lymphocytes, elevated ALT and AST, decreased neutrophils, elevated alkaline phosphatase, increased blood creatinine, and decreased calcium. The application carried priority review, breakthrough therapy, and orphan drug designations.

With traditional approval now in place, post-market surveillance obligations shift from confirmatory trial completion to routine pharmacovigilance and any outstanding label update commitments tied to the pediatric cohort's longer-term follow-up data.

Source: U.S. Food and Drug Administration, Drugs@FDA / What's New: Drugs RSS Feed, May 6, 2026.