Pediatric Study Plans Should Be Made Public, FDA’s Oncology Advisers Say

The US Food and Drug Administration’s pediatric oncology advisors want initial Pediatric Study Plans to be made public, or at least more transparent, to key childhood cancer researchers in order to maximize the benefit of a new law designed to encourage more oncology drugs for children.

The Research to Accelerate Cures and Equity for Children Act (RACE) amended the Pediatric Research Equity Act (PREA) to require pediatric investigations of certain targeted adult cancer drugs. The law applied to all original applications submitted on or after 18 August 2020 with new active ingredients based on a molecular mechanism of action.

Prior to the RACE Act, which was passed as part of the 2017 FDA Reauthorization Act (FDARA), few adult cancer drugs met the requirements for pediatric studies under PREA. (Also see "Pediatric Cancer Study Requirements Added To FDA User Fee Bill" - Pink Sheet, 12 July, 2017.)

The Pediatric Oncology Subcommittee of the FDA's Oncologic Drugs Advisory Committee discussed RACE’s initial impacts during a 22 May meeting. The committee consensus was that the law has raised awareness of and attention to the need for more pediatric oncology drug development and that initial research indicates more studies are getting underway. (Also see "More Pediatric Cancer Trials Conducted Due To RACE Act" - Pink Sheet, 20 May, 2024.)

However, subcommittee members were concerned with a lack of visibility into the research being planned or conducted under the law because initial Pediatric Study Plans (iPSPs) are considered proprietary information.

This lack of transparency makes it difficult to prioritize the most important research for what are typically rare cancers with limited patient populations. Tracking future outcomes of the RACE Act also will be more difficult, particularly if the adult cancer drug is not approved.

“We’re talking about a decision made in secret by one company to study childhood cancer in collaboration with a regulatory agency then has an impact on the ability of everyone else, all other childhood cancer researchers potentially, to study that same population,” said Malcolm Smith, associate branch chief, pediatrics at the National Cancer Institute’s Cancer Therapy Evaluation Program.

The look at iPSPs or other regulatorily-mandated pediatric study plans likely needs to occur well before a sponsor and regulator finalize the proposals, said Theodore Laetsch, of the Children’s Hospital of Philadelphia.

“My sense is that companies will be hesitant to renegotiate pediatric study plans with the FDA or the [European Medicines Association] after they’re established and some of these prioritizations across different companies will have to happen before those are established,” Laetsch said.

Industry May Be On Board

Sponsors often are hesitant to reveal proprietary information but there were indications from the pediatric ODAC’s industry representative, Bayer AG Senior VP and Head of Oncology Development Tara Frenkl, as well as Genentech, Inc. Program Director for Regulatory Affairs Ruchi Gupta, who gave an industry presentation at the meeting, that they may be amenable to the additional transparency idea.

Gupta said industry needs help determining the studies to prioritize when there are multiple same-in-class molecules being developed.

“It would be helpful for FDA to develop a process for prioritization across industry either through multistakeholder meetings, more transparency and flexibility when engaging with sponsors,” Gupta said. “In addition, it could be helpful to have specific iPSP procedures that will streamline the review of iPSPs that are competing with same-in-class molecules … Similarly, it will be helpful to take the holistic approach to set realistic targets for the minimum patient numbers required for conducting pediatric studies and number of pediatric indications to be studied.”

“We need to shift mindsets across to take a portfolio approach internally and externally and find a path for prioritization to address some of the major challenges posed by the changes in regulation and benefit the children in need,” she added.

But FDA May Not Have Much Flexibility

However, the FDA may not have the authority to be more transparent, particularly if the company or companies involved do not want to make their information available to others.

FDA leadership acknowledged the issue is part of a broader tension the agency regularly confronts when handling what industry considers trade secrets, but many others consider important information society needs to advance health. (Also see "Pharma Could Lose Some Commercial Info Protections As Part of FDA’s Misinformation Campaign" - Pink Sheet, 7 October, 2023.)

“It may be outside of our purview, out of our area of control at this point, but I do think it is acknowledging that you’re in a situation where’s there’s a bit of a blinder happening, right,” said Martha Donoghue, FDA Oncology Center of Excellence associate director for pediatric oncology and rare cancers.

“But that’s not unique necessarily even to these regulations,” she added. “I think there are many instances where there are ongoing studies happening that others are not aware of until, a publication occurs or something like that. So, I do think it goes beyond this issue. But it’s still important to acknowledge for FDARA as well.”

Address Cell and Gene Therapy, Combo Treatments

Moving forward the ODAC pediatric subcommittee also asked the FDA to compile and report additional data points to track RACE’s success, including the amount of time between when the first adult trial and pediatric trial of a cancer drug are initiated. The median time has been 6.5 years for a drug to move from starting adult clinical trials to starting pediatric trials.

Advisors also want more data on the agents being studied due to RACE and whether the trials are enrolling.

One of the meeting’s outside speakers, Brenda Weigel of the University of Minnesota, wanted data on the number of adolescents enrolled in adult cancer trials due to new allowances under RACE and whether that is impacting decisions to study the drugs in younger patients.

The advisory committee also asked that the FDA consider better defining molecularly targeted therapy so that the RACE Act’s intent could more closely align with new fields like cell and gene therapy.

Subcommittee members also said more guidance on combination therapies was needed.