Pink Sheet - Time To Simplify US FDA’s Expedited Pathways? It Won’t Be Simple

Michael McCaughan | September 27, 2021

US Food & Drug Administration Oncology Center of Excellence Director Richard Pazdur thinks the time is right to simplify the number of “expedited” pathways that FDA and drug sponsors use as part of the regulatory process.

Pazdur has emphasized that point as part of an initiative launched by Friends of Cancer Research last fall to build on the success of the “Breakthrough Therapy” designation process launched almost a decade ago. In addition to working on tangible steps to optimize that pathway, Pazdur has used the effort to call for a rethinking of the menu of expedited programs overall. (Also see "US FDA's Presubmission Expedited Regulatory Programs Eyed For Streamlining" - Pink Sheet, 8 Feb, 2021.)

He reiterated those arguments during a 20 September FOCR webinar to release a “White Paper” as part of the “Beyond Breakthrough” initiative.

The discussion underscored the wisdom of simplifying the menu of pathways offered by the agency to expedite drug development. What was left unsaid, however, underscores why simplifying regulatory pathways will not be a simple task.

Pazdur is urging a model that focuses on the “goals” of the various pathways and designations FDA offers for sponsors of novel treatments for unmet needs, with an idea of moving towards something like an “early Breakthrough” to trigger closer engagement in drug development and a “late Breakthrough” that focuses on the application review phase.

“Should we try to simplify some of these pathways?” Pazdur asked, rhetorically. “Rather than looking at all these programs, perhaps we need some simplification and actually concentrate on what are the core messages of these programs.”

The case for simplification was underscored early in the meeting by a different presenter: oncology reviewer Martha Donaghue (who leads OCE’s “Project Beyond Breakthrough”). In describing the impact of the Breakthrough pathway over the past decade, she suggested its most important legacy goes far beyond the letter of the law.

“It has been a really important impetus for us as regulators in terms of what we view our role as, frankly ... from one that is responsive to sponsors actions and questions to more of a collaborative proactive creative problem-solving approach that we can now bring to bear through the interactions we have when we discuss drug development of BTD drugs,” she said.

“The changes have been so profound that they’ve trickled down to non-BTD drugs. I think that we really have realized quite a bit of change,” Donaghue added.

End Of The Road For Fast Track?

Pazdur specifically described “Fast Track” in terms that suggest he thinks it has outlived its usefulness. Fast Track was created 20 years ago, Pazdur noted. “Drug development has changed dramatically during that period of time,” he observed.

“Fast Track probably has very little meaning to people at this time, but sponsors ask for it,” and those requests “take up our bandwith, and our time and energy.”

Rather then retain the various designations, Pazdur proposed “keeping the essence of what is the true goal” – namely, getting effective treatments for unmet medical needs to patients as quickly as possible. He quipped that the only people who really understand all the requirements and nuances between different designations like Fast Track, Breakthrough and RMAT “are people in the regulatory departments at pharmaceutical firms.”

The current system involves “unnecessary paperwork and duplication of paperwork. ... It becomes almost a chess game for the pharmaceutical companies and the FDA of who has what and what move is next.”

Of note, Biotechnology Innovation Organization CEO Michelle McMurry-Heath agreed with that idea – at least in principle. “I think it is high time to look at simplification. These decisions are on a spectrum ... and all of the spectrum is about how you make risk benefit assessments. Simplification would make it I think easier for patients and for sponsors as they are trying to pursue it.”

But equally of note, she did not provide any specifics like Pazdur did about which pathways are now redundant. Instead, she pivoted to a call for greater public education and understanding of the Accelerated Approval pathway – another topic on which Pazdur has a wealth of ideas for enhancements.  (Also see "Accelerated Approval: US FDA Wants Comprehensive Development Plan From Oncology Sponsors" - Pink Sheet, 21 Sep, 2021.)

Similarly, former Roche Holding AG/Genentech, Inc. executive Sandra Horning (now on the faculty at Stanford) expressed agreement for the concept of simplification and transparency, with an emphasis on better explaining the programs to the American public rather than specific suggestions for pathways to eliminate.

That should not be too surprising. After all, BIO’s members are the ones seeking “Fast Track,” and clearly see some value in obtaining the designation as a way to highlight a research project for investors. In fact, at least two companies – AVEO Pharmaceuticals, Inc. and Inventiva S.A. – issued press releases in the days after the FOCR event announcing Fast Track designations for early-stage projects.

Similarly, the newest expedited pathway, RMAT (Regenerative Medicine Advanced Therapy), was created by Congress at the behest of regenerative medicine companies eager to have a special pathway to highlight their sector – even though it seemed at the time to be redundant given the existence of “Breakthrough.”

The concerns about needless, duplicative paperwork didn’t matter much, particularly since inclusion of the new program was the price exacted by then Senate Majority Leader Mitch McConnell, R-Ky., to permit final passage of the 21st Century Cures Act in 2016. (Also see "Regenerative Medicine In Cures: Conditional Approval Dropped In Lieu Of ‘Breakthrough’-Style Approach" - Pink Sheet, 1 Dec, 2016.)

Eliminating a pathway like that may well be a logical idea, but it would also involve FDA in a chess game of a very different sort.

https://pink.pharmaintelligence.informa.com/PS145004/Time-To-Simplify-US-FDAs-Expedited-Pathways-It-Wont-Be-Simple