Speed vs. Certainty When it Comes to Expedited Regulatory Review of Colorectal Cancer Therapeutics

The FDA has long used expedited regulatory paths (ERPs) to speed up the availability of promising treatments for critical illnesses. The Journal of Managed Care & Specialty Pharmacy released a study in August that looked at how these routes have changed the way colorectal cancer (CRC) is treated. CRC is the second biggest cause of cancer death in the United States. The results show that precision oncology has come a long way, but there are still big problems for payers, doctors and patients.

The FDA has four ERPs available for therapeutics, which are Fast Track Designation, Priority Review, Breakthrough Therapy Designation and Accelerated Approval. While ERPs speed access, they do so by lowering the evidentiary threshold for approval. Many CRC drugs have been cleared based on surrogate endpoints or single-arm trials, with confirmatory studies required post-approval.

However, as Danea Horn, Ph.D., from the Center for Translational and Policy Research on Precision Medicine, Department of Clinical Pharmacy, University of California, San Francisco, and her team point out, one-third of all currently available CRC drugs still await confirmatory trial results. Among drugs approved since 2018, none have yet secured full FDA approval.

This evidence gap can persist for years. Developers typically have three to seven years to complete confirmatory trials. In some cases, approvals have been revoked when later studies failed to demonstrate clinical benefit. For managed care organizations, this creates uncertainty in formulary placement, utilization management, and long-term cost-effectiveness

To explore how these pathways have influenced the pharmaceutical landscape, a cross-sectional study was conducted by Horn. The study analyzed all 24 FDA-approved drugs for CRC as of December 2024. The methodology focused on approval trends, comparing the period before and after the 2012 passage of the FDA Safety and Innovation Act (which created the Breakthrough Therapy Designation).

Strikingly, 75% of these therapies were cleared through at least one ERP. The use of ERPs rose sharply after the 2012 FDA Safety and Innovation Act, which also expanded the use of surrogate endpoints like progression-free survival.

Before 2012, 63% of CRC drugs used an expedited pathway; after 2012, that figure climbed to 81%. Since 2018, every new CRC drug approval has gone through an ERP. Accelerated Approval has been the most common route, accounting for 72% of all expedited CRC approvals.

The research also highlighted a parallel trend: the growing reliance on molecular diagnostics to guide treatment. Only 25% of CRC drugs approved before 2012 required a companion or complementary diagnostic test. That number rose to 75% after 2012, and since 2018, every new CRC treatment has been linked to biomarker testing.

This is part of a larger trend toward precision medicine, which uses treatments that target specific genetic abnormalities or tumor markers. For instance, when patients are chosen based on cancer biomarkers, the response rates to immunotherapy in CRC might go from almost nil to 40%. However, the combination of diagnostics and medicines makes coverage decisions more difficult because different FDA sections control pharmaceuticals and tests, and they may not be approved at the same time.

Many CRC medications on the market don't have clear survival data, so payers must find a balance between letting patients use them and taking financial and clinical risks. Some strategies are contracts based on outcomes, coverage with evidence development and adaptable formularies that change as new data comes in. Using real-world evidence from claims and electronic health records could help fill in the gaps when confirmatory trials are delayed.

Almost every CRC drug now requires biomarker testing; coverage policies must integrate pharmacy and medical benefits. Ensuring timely access to companion diagnostics is essential to avoid inappropriate prescribing. Managed care pharmacists will need to verify testing before dispensing and develop biomarker-based utilization criteria.

The FDA has lately been given increased power to enforce standards for confirmatory trials and speed up the process of removing medications that don't show any benefit. The report noted that while expedited approvals allow patients earlier access to potentially life-saving therapies, they also create added challenges for providers and payers, including clinical uncertainty, greater complexity and rising costs.