FDA on Hot Seat for Clinical Trial Deaths

Did agency act too quickly on CAR-T study?

When three cancer patients died earlier this year from swelling of the brain while receiving the experimental immunotherapy CAR-T (Juno Therapeutics), the FDA promptly halted the clinical trial. Five days later, the hold was lifted—a turnaround so fast that it stunned the pharma industry. On November 23, Juno reported that two more patients were dead.

“In light of what happened, I think the FDA really dropped the ball,” Maxim Jacobs, a health care analyst at Edison Investment Research, told STAT News.

“What did the FDA review during that period from when the hold was announced to when it was lifted? What exactly was the decision-making process? What was the logic behind going so quickly towards lifting the hold?” Jacobs asked.

The FDA has declined to comment on its decision. But the debate over whether the agency moved too quickly on the CAR-T study has raised questions about whether it is sufficiently forthcoming about how it makes its decisions, according to the STAT report.

Jacobs and other experts have pointed out that there is no way to know where the FDA might have slipped up in the case of CAR-T. That’s because the agency has drawn a curtain on how it decides whether to halt and restart a clinical study, STAT notes.

It took the FDA only five days to lift its hold on the CAR-T trial. In contrast, a 2015 analysis found that, between 2008 and 2014, these holds were in place for a median period of eight months.

In a written statement, the FDA said that because of the “great promise” of CAR-T and other cellular therapies, the agency does “everything possible to assist sponsors in advancing clinical development programs in an effort to bring promising therapies to patients.” The statement also said that the agency “constantly looks at the risk–benefit profile of experimental therapies and when we have concerns about the risks, we may place the clinical trials on hold.”

Experts said it would be premature to call for the FDA to shut down Juno’s other trials or other companies’ CAR-T studies, according to STAT. But Jacobs said that, given the alarming safety problems, the FDA should make sure that companies are collecting extensive data before they move on to later-stage trials or seek approval.

“We’ve really been rushing into things with these CAR-Ts,” Jacobs said.

In March, the FDA proposed creating new databases that would allow it to monitor the safety of experimental CAR-T treatments across different trials. At that time, the agency said it planned to collect data, store them in a database, and analyze them across the different studies, according to the STAT article. But such plans could be stalled as the agency braces for upheaval in the aftermath of the presidential election. Legislation that could reduce the requirements for clinical trials may be passed in the next session, and the Trump administration is expected to call for further deregulation.

The pending legislation would allow the FDA to approve a drug based on phase 1 data.

Source: STAT News; November 23, 2016.