P302: Postmarketing Commitments for Companion Diagnostic Development in Oncology Drug Approvals (2012–2025)
Poster Presenter
Grace Collins
Manager, Regulatory & Data Insights
Friends of Cancer Research United States
Objectives
Evaluate how postmarketing commitments (PMC) have been used to support the development, validation, and availability of in vitro diagnostic (IVD) tests intended to be used as companion diagnostics (CDx) for novel oncology therapies approved by the FDA from 2012–2025.
Method
We reviewed publicly available FDA approval letters, labels, and review documents published on Drugs@FDA for novel oncology therapies approved from 2012–2025 to identify and assess trends in the use of PMCs related to the development, validation, and availability of IVDs intended to be used as CDx.
Results
For the 172 novel oncology drugs approved 2012–2025, we collected PMC descriptions, final report due dates, indications (cancer type and biomarker defined population) from documents published on Drugs@FDA, and used OncoKB’s database to identify drugs for which pre-treatment molecular profiling is required for optimal patient selection (i.e., precision medicines).
Most approvals (n=95/172, 55%) were precision medicines requiring diagnostic testing for patient selection. Of these, 20 drugs had a PMC (22 PMCs subject to reporting under Sec. 506B) focused on analytical and clinical validation of an IVD essential for the safe and effective use of the therapy, with a notable increase in recent years (10 drugs with a diagnostic PMC approved 2024–2025). Labels for 16 drugs stated no FDA-approved test was available for the indicated population. The remaining 4 drugs had a premarket approval application contemporaneously reviewed and approved by CDRH.
For the 20 drugs with a diagnostic PMC, we collected estimated prevalence data from published literature and categorized each drug’s indicated population(s) by rarity. Most were ultra-rare (n=7/20, 35%; <1 case per 100,000), rare (n=6/20, 30%; <6 per 100,000, or small molecular subset of a rare cancer), or less common molecular subset (n=6/20, 30%; =6 per 100,000 overall cancer, but biomarker-defined subgroup ~1–5% of common tumor type). Two drugs targeted populations considered common. Final reports for diagnostic PMCs in ultra-rare indications were due a median of 948 days after approval, more than double the median days for diagnostic PMCs in rare (414), less common (372), and common (166) indications.
Regulatory review documents provided FDA’s rationale for approving drugs despite the lack of CDx availability. Reasons included the limited risk of inappropriate patient selection, demonstrated therapeutic efficacy, availability of non-CDx or standard of care tests, rarity of the patient population, and high unmet need.
Conclusion
In recent years, the FDA has demonstrated its willingness to exercise regulatory flexibility by approving drugs prior to CDx availability while requiring PMCs focused on development and validation of IVDs intended to be used as CDx. While contemporaneous approval of a drug and CDx remains the ideal approach, these findings suggest postmarketing approaches may be particularly valuable for rare and ultra-rare cancers where obtaining the necessary samples for analytical and clinical validation is challenging. Postmarketing activities can be leveraged to provide timely access to novel therapies while ensuring IVD tests continue to be developed to inform labeling.
