A Look at the Clinical Benefits of the FDA’s Expanded Access Program

A single-center evaluation of the FDA's Expanded Access program indicated broad use of the program among the center’s patients, including a large percentage of pediatric patients.

A single-center evaluation of the US Food and Drug Administration (FDA) Expanded Access program indicated broad use of the program among the center’s patients, including a large percentage of pediatric patients.

Despite the population of patients being heavily pretreated, “a small but meaningful proportion of patients appeared to benefit,” reported Noah Z. Feit, BA, of Weill Cornell Medical College, and colleagues, in a research letter published in JAMA Oncology.

According to the FDA, Expanded Access, sometimes called “compassionate use,” is a potential pathway for patients with an immediately life-threatening or serious disease or condition to gain access to an investigational medical product for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.

However, there are little data about outcomes associated with use of this program, according to Feit and colleagues. To evaluate safety and efficacy, the study included all single-patient use applications approved by Memorial Sloan Kettering’s Institutional Review Board and the FDA from 2012 to 2018. Response was assessed by a physician at 6 weeks; any patient who had clinically deteriorated prior to this 6-week mark was considered a nonresponder.

There were 208 single-patient use applications approved, and products were administered in 185 instances to 179 patients. Patients had a median of four prior treatments. About two-thirds (65.9%) of the patients were adults.

“Children represented 34.1% of the cohort despite being only approximately 2% of the patients seen at the center in 2017, suggesting single-patient uses may provide an important means of pediatric drug access,” the researchers wrote.

Included patients had 43 cancer types, of which 57.9% were solid tumors. Among the solid tumors included were neuroblastoma (15.3%), lung (7.9%), primary brain (7.9%), breast (5.9%), and others (20.8%).

A variety of investigational therapies were administered, such as kinase inhibitors (28.8%), naked antibodies (12.5%), and allogeneic cell therapy (12.0%). Genomic data were listed as the reason for the single-patient use application in about one-third (38.0%) of cases. The median time from request to treatment was 19 days.

The researchers excluded 26 patients who received the therapies while in remission or with minimal residual disease.

Among the 159 remaining patients, 1 out of 5 patients responded (20.1%). The best response varied by patients and products, but occurred most commonly with kinase inhibitors (16.7%), allogeneic cell therapy (17.6%), and antibody-drug conjugates (5.3%).

At 6 months, the estimated progression-free survival rate was 38.9%; that decreased to 24.5% at 1 year. Median overall survival was 11.4 months.

A little less than one-third of patients had one or more treatment-related serious adverse events (19.1% in pediatric patients and 35.3% in adults). No treatment-related deaths occurred.

Feit and colleagues noted several limitations with the study, including its single-center and retrospective design.

Lisa Kearns, MS, MA, a senior research associate of the division of medical ethics and a member of its Working Group on Compassionate Use and Pre-Approval Access at NYU School of Medicine, told Cancer Network that this study and any report on single-patient use of investigational products is important because there is such a dearth of data on the topic.

“The FDA reports the number of requests it receives and allows to proceed, but there is very little out there on the number of requests [that] physicians or manufacturers receive and whether they’re approved or declined,” Kearns said.

Research in the Working Group has shown that lack of knowledge about the existence of the Expanded Access program and how it operates are obstacles to access, according to Kearns.

“Thus, the fact that 66 different investigational products were provided to 179 patients shows that, at least in this specific oncology context, Expanded Access is a practicable access route for patients who are ineligible for clinical trials,” she said. “The breadth of products also shows the importance that knowledgeable physicians plays in Expanded Access.”

Kearns also highlighted the fact that the median time from initial request to treatment was less than 3 weeks.

“The FDA Expanded Access program often gets dinged for being a bureaucratic obstacle to experimental drugs; this quick turnaround shows that the bad rap is undeserved,” Kearns said. “Keep in mind that in a median 19 days, 1) patients’ physicians requested agents from manufacturers/sponsors; 2) manufacturers processed, considered, and responded to the requests; 3) the physicians got the FDA to sign off on the treatment protocols; 4) the physicians’ institutional review boards … signed off on the treatment protocols, as well as the informed consent documents, the provisions of which are federally regulated for Expanded Access to ensure that patients understand the full ramifications of taking experimental agents that may not have undergone extensive clinical testing; and 5) then procured and administered the agents.”

Finally, Kearns also pointed out that the Expanded Access program collected adverse event data, something not required by the Right to Try Act.

“This alternative pathway to the FDA Expedited Access Pathway requires only an annual summary of adverse events, which means [that] a bad outcome in a patient that would inform the treatment of future patients may not be known for months and months,” Kearns said. “This exposes patients to undue and unnecessary risks.”