Key Decision Points for Recent Oncology Approvals

In keeping with our theme of forking paths, I would like to highlight three critical decision points illustrated by these approvals:  the decision to participate in Project Orbis, the submission of Assessment Aids, and the use of the Real Time Oncology Review process.   

Project Orbis

Two of the recent approvals highlighted above used Project Orbis.  This program was initiated by the FDA Oncology Center of Excellence in May 2019 to establish a framework for the concurrent submission and review of oncology drugs among international regulatory partners. The collaboration has been successful in providing cancer patients with earlier access to treatments across different countries, and in reducing overall regulatory approval times. 

The project leverages international pivotal clinical trials to assess the safety and efficacy of cancer drugs, fostering the establishment of uniform global treatment standards. By promoting simultaneous reviews and approvals, Project Orbis facilitates faster access to new therapies, thereby expanding the availability of innovative cancer treatments to a larger global market. For more detailed information, you can visit the Project Orbis page. 

Decision point for sponsors: When considering project Orbis, sponsors should consider general challenges inherent in multinational submissions from data and regulatory perspectives with specific emphasis on the impact of accelerated timelines on coordination of regulatory advice, gap analysis of submission requirements, and management of information requests.  

Assessment Aid

Assessment aids are based on the FDA’s multidisciplinary review template but are drafted by the applicant.  While these submissions are voluntary, they benefit both sponsors and the FDA by providing a valuable focusing tool that highlights critical submission information at a level of detail that “leads to a more dynamic review process where key regulatory questions can be answered more thoroughly and effectively.”  A strong Assessment Aid serves not just as a summary of the NDA/BLA, but also as a statement of sponsor position, reducing ambiguity and allowing the FDA to more effectively perform their analysis. A key expected benefit of this approach is a reduction in information requests.  

Decision point for sponsors: As the Assessment Aid is generally submitted with the NDA/BLA, a key decision point for sponsors is whether the extra effort to produce the document is worth the benefits that arise from a more focused FDA review.  The answer to this question may lie in advanced preparation, particularly in the form of quality written summaries that can be extracted and adapted to produce an effective assessment aid.

Real Time Oncology Review

Lastly, we highlight the use of Real Time Oncology Review (RTOR).  The RTOR program was designed to streamline the review of promising new oncology treatments, while allowing Sponsors an earlier application review start.  This provides an opportunity for early Agency engagement to proactively identify potential deficiencies and review top line clinical data upon availability as opposed to following the completion of a final clinical study report.  The FDA evaluated the approval time for oncology applications and found that those using the RTOR process had a shorter median submission review to approval time of 3.3 months.   For an extensive overview of the challenges, benefits, and key decision points related to RTOR, please see the recent blog drafted by the MMS Regulatory Strategy and Operations teams.   

Decision point for sponsors: One of the main challenges of the RTOR process is the management of the Information Requests (IRs) from the FDA in parallel with ongoing submission planning. The frequent flow of IRs also involves tight turnaround times, typically within 24 to 48 hours.  These IRs may also impact future components of the rolling submission, which will need to incorporate the FDA’s feedback.