Use of Real World Data to fulfil post-approval requirements

A large pharma client submitted a New Drug Application to FDA’s Center for Drug Evaluation and Research (CDER) for a targeted therapy, which was indicated for a rare molecular subtype of a solid tumour. In order to identify patients who would be likely to benefit from the targeted therapy and to help ensure the safe and effective use of that therapy, a Premarket Approval (PMA) application for a companion diagnostic was submitted in parallel to FDA’s Center for Devices and Radiological Health (CDRH).

While the targeted therapy received accelerated approval, major deficiencies were identified in the companion diagnostic filing, which resulted in the withdrawal of the PMA. Consistent with FDA’s accelerated approval pathway and requirements for precision medicines, a post-marketing commitment was assigned to the targeted therapy necessitating the inclusion of a companion diagnostic within the labelling. 

The Sponsor had to resubmit the companion diagnostic application with additional clinical analyses and attend a series of FDA meetings involving both CDRH and CDER including an appeal process. The therapy was then granted conditional approval, requiring a post-approval study to confirm the clinical outcomes of the companion diagnostic in the post-market setting. Due to the rarity of the tumour’s molecular subtype, it would be extremely challenging to achieve patient enrolment in a post-approval clinical trial.

ICON’s Regulatory Consulting Solutions (RCS) team proposed using a clinico-genomic, real-world database to show outcomes in the real-world clinical setting instead of designing and initiating a new clinical trial. This allowed the Sponsor to gather required data without requiring new enrolment within an exceedingly small target population. 

The RCS team developed the strategy around the real-world data option to support the statistical analysis plan and discussed with the agency on behalf of the Sponsor. Following further negotiations, CDRH accepted the proposal to use real-world data to fulfil the post-approval study requirement, along with supplementary analyses from an ongoing non-US clinical study.

The negotiation with regulatory agencies to leverage real-world data saved the Sponsor substantial costs, time, and the effort of conducting a clinical trial while also enabling access to the companion diagnostic. Importantly, this solution also provided access to a targeted therapy for eligible patients. 

ICON supported the resubmission of the companion diagnostic, coordinated the many agency meetings and managed negotiations that led to the eventual fulfilment of the targeted therapy’s post-marketing commitment. Our strong partnership and collaboration with the Sponsor radically simplified their fulfilment of the regulator’s post-approval expectations, setting a precedent to leverage real-world data in future drug and device development and approval.