FDA's oncology office uses advisory committee to spotlight timely accelerated approval confirmation

An upcoming meeting of the FDA’s oncologic drugs advisory committee is slated to serve as a reminder for cancer drug developers that the agency is keeping a close eye on accelerated approvals.

External experts invited by the FDA will discuss during a meeting Thursday two accelerated approvals by Acrotech Biopharma. The two nods are for Folotyn and Beleodaq in relapsed or refractory peripheral T-cell lymphoma (PTCL), granted in 2009 and 2014, respectively.

Both indications have long passed their original timeline agreed with the FDA for providing confirmatory trial data to verify the drugs’ clinical benefit. And the final report of data from a new confirmatory trial proposed by Acrotech isn’t expected until 2030.

The FDA’s oncology staffers are now asking its advisers to weigh in on next steps for the two drugs and provide suggestions about facilitating the timely completion of confirmatory trials for future accelerated approvals.

“The overall goal will be the continued optimization of the accelerated approval process with a focus on decreasing the amount of time to verify (or fail to verify) clinical benefit, while continuing to provide early availability of promising oncology products,” the agency said in its agenda.

The FDA oncology department’s heightened scrutiny on accelerated approvals can be traced back to late 2020, when Bristol Myers Squibb withdrew Opdivo in third-line small cell lung cancer as part of an industrywide evaluation by the FDA. During a three-day advisory committee meeting in 2021, the FDA put on display its crackdown on some so-called “dangling” accelerated approvals, where a drug’s postmarketing trials had failed to prove clinical benefit.

This time, the FDA appeared to be using the public platform to remind biopharma companies to complete their verification of accelerated approvals on time, while the indications involved are minor from a commercial standpoint. PTCL is a relatively rare type of aggressive blood cancer, accounting for about 10% of all newly diagnosed non-Hodgkin lymphomas.

And the agency’s stance on delayed confirmatory trials isn’t new. The FDA’s oncology chief Richard Pazdur, M.D., previously called the time between an accelerated approval and either success or failure in confirmation of efficacy “a period of vulnerability” that the agency is trying to minimize.

In a separate briefing document the FDA prepared for Thursday’s meeting, the agency once again highlighted that potentially vulnerable period.  

“Reducing this time to verification or refutation of clinical benefit through timely completion of confirmatory trials can reduce the risk and exposure to such drugs,” the FDA said of drugs that may not later prove to provide enough clinical benefit.

Empowered by the Food and Drug Omnibus Reform Act that passed in 2022, the FDA’s oncology drug reviewers have lately required that confirmatory trials be underway at the time of approval.

Of the 187 accelerated approvals the FDA has granted in oncology, the Folotyn and Beleodaq nods now have the longest outstanding postmarketing requirements for a confirmatory trial, the FDA noted.

Folotyn and Beleodaq got their approvals based on single-arm tumor shrinkage data, and both showed an overall response rate below 30% in patients with previously treated PTCL. After an originally designated confirmatory study struggled to enroll patients, Acrotech proposed the phase 2/3 SPI-BEL-301 trial as the confirmatory trial, which will test different combinations for the drugs against the traditional CHOP regimen in newly diagnosed PTCL.

A phase 3 trial would have started early in 2022, but the FDA last year raised questions about the doses identified in phase 1 studies. Instead, the agency requested an additional randomized phase to find the optimal dose before entering the phase 3 stage. Now, Acrotech is just beginning to launch the first part of the phase 2/3 study.