US FDA Expanded Access Pilot Launching Soon With Staffing Questions Unanswered
Executive Summary
New call center is designed to help physicians navigate the expanded access pathway for oncology products, but FDA officials are unsure about how much interest it will generate.
Project Facilitate, the US Food and Drug Administration's pilot to help patients navigate the expanded access system, is set to launch later this month amid questions about the public interest it may generate.
Agency experts will be available to answer phone calls during business hours from physicians and help them complete the necessary forms and obtain needed authorizations for oncology-related single-patient IND applications. But because the FDA has no experience running a call center for expanded access questions, agency officials have no idea how many employees to devote to it.
Richard Pazdur, director of the Oncology Center of Excellence, said a couple existing staffers would rotate through the call center each day until the agency gauges the call volume. Permanent staff may be added should they be needed after the initial phase.
Some on Pazdur's staff seem to be fearing the worst in terms of the incoming workload.
"Dr. Pazdur's worried that we're not going to get enough calls," OCE Deputy Director Gideon Blumenthal said during a 16 May public meeting on Project Facilitate. "I think we're worried that we're going to be flooded with calls. We'll see how it all shakes out."
Some sponsors already are seeing increases in expanded access activity and warned more may be coming with the additional attention on the program. A representative of Pfizer Inc. said during the workshop that in 2018 the company received about 4,800 expanded access requests globally, but received about 1,600 in the first quarter of 2019. The FDA also received about 1,800 requests annually from fiscal years 2012 to 2016.
The FDA decided to launch Project Facilitate amid lingering confusion and misinformation about the expanded access program. The public meeting was intended to solicit feedback on improvements to the existing system and identify gaps in patient and provider knowledge of it. (Also see "‘Project Facilitate’: US FDA Plans May Meeting On Expanded Access Call Center" - Pink Sheet, 15 Mar, 2019.)
Pazdur told the workshop that Project Facilitate also is an effort to open the expanded access program to more patients.
"Traditionally and conventionally, people go on expanded access programs or single-patient INDs when their doctors tend to be investigators for a particular drug," he said. "So this produces some inequity in the system.
"This is an attempt to facilitate the existing program that is here, but to really make it a much more accessible program to all patients in the United States."
Misconceptions about the difficulty gaining approvals for expanded access and thinking that the agency was a barrier led to passage of right to try legislation. The 2018 measure allowed patients to petition sponsors about providing expanded access without gaining FDA approval. Since the law's enactment, there have been few disclosed uses of the pathway. (Also see "Gottlieb: Lack Of Compromise On Right-To-Try Bill Is 'Interesting Lesson In Politics' For Stakeholders" - Pink Sheet, 15 May, 2019.)
Documenting Company Denials – If Reasons Given
The FDA intends to gather much more information about expanded access programs through Project Facilitate than currently is available, including a more accurate description of the total number of requests and reasons companies deny them, if provided. The agency also wants efficacy and safety data from patients and physicians who receive drugs through expanded access.
"We don't know how many patients are asking for these drugs," Pazdur said. "They may go to the drug company and the drug company could say no to 100 patients and then say yes to patient 101. Why?"
The FDA approves more than 99% of the requests received each year, however, the number of requests not submitted because of confusion or burden of the process is unknown. (Also see "FDA's Compassionate Use Initiatives: Web Clearinghouse, Guidance Documents" - Pink Sheet, 16 May, 2016.)
The complexities surrounding expanded access programs gained attention in 2014 when Chimerix Inc. refused requests by Josh Hardy, a seven-year-old infected with adenovirus, for expanded access for brincidofovir. Hardy had been infected following a bone marrow transplant for cancer and his mother started a social media campaign that quickly gained a massive following and media attention.
Eventually, Hardy was enrolled in a 20-patient trial, but there were questions as to why Hardy's case merited consideration after Chimerix had ended its expanded access program for the drug two years earlier and had denied 300 expanded access requests. (Also see "FDA Crisis Management: Behind-The-Scenes Of Josh Hardy's Compassionate Use" - Pink Sheet, 29 Oct, 2015.)
Pilot Will Attempt To Streamline Process
Project Facilitate will become the single contact point for oncology-related expanded access applications. Staff will help physicians fill out the FDA forms and provide options for Institutional Review Board access. A full IRB board review is not necessary for approval a single-patient IND application. The IRB chair is allowed to sign-off, the agency said.
Pazdur also said the agency will keep previously approved protocols on file for potential reuse should a similar application arrive and input physician CV information into its database.
The FDA will use the Expanded Access Navigator created and administered by the Reagan-Udall Foundation as a resource when advising physicians and patients on EA requests. The foundation created the navigator as a central location for company expanded access information, although FDA and foundation officials said during the workshop that some companies still have not posted their policies as required by the 2016 21st Century Cures Act. (Also see "Reagan-Udall Expanded Access Navigator Ready To Launch" - Pink Sheet, 11 May, 2017.)
The FDA also is working to calm industry fears about expanded access. Agency officials have used data obtained through expanded access trials to help support regulatory approvals. Advanced Accelerator Applications SA's Lutathera (lutetium Lu 177 dotatate) included expanded access data in its application, which was approved in January 2018 for treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. (Also see "Expanded Access Data Supported Lutathera Approval, US FDA Notes" - Pink Sheet, 29 Jan, 2018.)
Despite the opportunity, some sponsors still worry that adverse events seen in expanded access patients may hurt a drug's chances of approval. (Also see " Expanded Access: US FDA Told To Increase Regulatory Clarity, Early Interactions With Sponsors" - Pink Sheet, 8 Nov, 2018.)