Breakthrough Requests: FDA Adds Quick Screen To Pare Workload
This article was originally published in The Pink Sheet Daily
Executive Summary
Hope is to quickly reject obviously inadequate designation requests, but few meet criteria for dismissal so far.
FDA has instituted a screening system to weed out deficient breakthrough designation requests and help reduce the workload created by the popular program.
But so far it has been difficult to make a significant dent in the growing list of products sponsors believe to be potentially transformative therapies and thus deserving of the increased agency involvement during development that the breakthrough program promises.
Office of New Drugs Director John Jenkins said the screening process was implemented as a pilot project over the summer in the hopes of quickly removing those designation requests that obviously are not breakthroughs.
“If we see one that’s just based on animal data and there’s no clinical data to confirm that promise, then that’s an easy rejection,” Jenkins said Nov. 12 during the Biopharma Congress, which was sponsored by the Friends of Cancer Research and Prevision Policy.
Jenkins said after the panel discussion that screeners also could flag requests that on their face are not an improvement or do not use a reliable endpoint, in addition to those with data on so few patients that the evidence cannot be interpreted reliably.
But he also indicated that most breakthrough requests are not so easily judged. The number of applications meeting the screening criteria still is relatively small, Jenkins said.
Breakthrough’s popularity has required FDA to come up with ways to better handle designation requests.
As of Sept. 30, FDA had received 337 breakthrough requests, granted 103 and denied 181 since the program’s 2012 launch (Also see "‘Breakthrough Therapy’ Designations" - Pink Sheet, 2 Nov, 2015.).
The number of potential drugs showing early clinical evidence of substantial benefit is exciting for the agency and stakeholders.
However, the work involved with breakthrough designees is substantial (Also see "‘Breakthrough’ Therapies: Information Requests A Sign Of Workload Problem?" - Pink Sheet, 13 Apr, 2015.).
The quick screen idea emerged following an April meeting at the Brookings Institution, where stakeholders discussed a number of issues with the breakthrough program (Also see "‘Breakthrough’ Request Success Tied To Data Reliability" - Pink Sheet, 4 May, 2015.).
Among its biggest problems has been what have been characterized as frivolous requests – applications that have little chance to be designated, but are submitted anyway (Also see "‘Breakthrough’ Fee Eyed As Deterrent To Frivolous Requests" - Pink Sheet, 4 May, 2015.).
Pre-Request Teleconference Also Not Popular
Along with the screening program, FDA offered to arrange a brief teleconference between sponsors and review divisions to talk about potential breakthroughs before requests are submitted.
Jenkins didn’t think many sponsors had used the teleconference or the division’s advice when told the breakthrough request was not ready.
He said the agency wants sponsors to better understand the designation threshold so effort is not wasted.
“Sometimes it’s about getting more data,” Jenkins said. “And often when you bring more, the confidence that that’s a real signal of substantial improvement goes up and we feel more comfortable designating a product.”
Joanne Palmisano, VP of regulatory affairs for Boehringer Ingelheim GMBH, said most companies likely are quite confident that their products are worthy of a breakthrough designation. She said there needs to be a better understanding of FDA’s interpretation of the requirements.
“I think some of this has to be fostered by an appreciation of what is adequate data to support a prediction of eventual efficacy and maybe some early safety data to reduce some uncertainty,” Palmisano said during the conference.
“It may not be challenging for large companies which have very sophisticated drug development, but it may be a challenge for small and medium size companies, particularly companies that are powered by venture capital, where there clearly is a need to have that breakthrough designation in order to get additional funding or to keep their stakeholders involved.”
Investors have embraced the breakthrough program because of FDA’s willingness to devote more resources to the product's development, and in part because of the prestige of having a designated product (Also see "Investors Like “Breakthrough” Therapies, But Real Test Still To Come" - In Vivo, 22 Dec, 2014.).
User Fee Would Change Industry-FDA Relations, Jenkins Says
Jenkins also said the idea to create a breakthrough user fee as a way of deterring unworthy requests, which has gained attention in recent months, would create more problems.
The agency is better off not having fees tied to specific pieces of its work, he explained.
“I have concerns about situations where we start having fees that are directly linked to a specific piece of work because of the dynamics that may cause in the system of how we relate with sponsors,” he said. “I like the system where it’s a broader approach to how we collect the fees.”
Breakthrough program adjustments could be among the issues discussed during prescription drug user fee reauthorization negotiations, which began in September (Also see "PDUFA Negotiations Begin With FDA Seeking Review System Reform" - Pink Sheet, 13 Oct, 2015.).