[Regulatory Affairs Professional Society]
By Zachary Brennan.
A new bipartisan bill reintroduced in the House and Senate in late February, which could ultimately be attached to the reauthorized Prescription Drug User Fee Act (PDUFA), seeks to close the loopholes biopharmaceutical companies use to skirt around clinical trial requirements for cancer treatments in pediatric populations.
Pediatric study requirements are included in both the Pediatric Research Equity Act (PREA), which requires biopharma companies to study their products in children under certain circumstances, and the Best Pharmaceuticals for Children Act (BPCA), which provides an incentive for drug companies to conduct US Food and Drug Administration (FDA) requested pediatric studies by granting an additional six months of marketing exclusivity.
As FDA explains: “In essence, BPCA is a carrot, an incentive to do something that may be beneficial. PREA is the stick of the legislator. Ultimately, PREA and BPCA have a shared goal of providing new pediatric information and drug labeling, and encouraging the appropriate use of medication to treat these patients.”
And though studies under PREA are mandatory and those under BPCA are voluntary, PREA requires studies only on the indication(s) under review, while the BPCA studies relate to an entire moiety and may include unapproved and different indications.
Dr. Lynne Yao, director of FDA’s Pediatric and Maternal Health Staff, said in 2013: “Before BPCA and PREA became law, more than 80% of the drugs approved for adult use were being used in children, even though the safety and effectiveness had not been established in children. Today that number has been reduced to about 50%.”
But problems have occurred as FDA has allowed sponsors to defer or forego pediatric studies, and as Yao explained, “deadlines for deferred studies have often been missed.”
In December, FDA officials also called for including adolescents in adult oncology trials.
RACE for Children Act
With about 900 treatments in the adult cancer pipeline making their way to market, but only a handful of those studied in pediatric cancers, the new Research to Accelerate Cures and Equity (RACE) for Children Act will look to ensure that FDA authority to require companies to undertake pediatric study plans pursuant to PREA “shall include instances when the molecular target of a drug developed for an adult cancer is germane to the growth and progression of a pediatric cancer.”
In addition, the bill will end the current exemption for companies from obligations related to undertaking PREA pediatric study plans when a drug has orphan status.
Nancy Goodman, author of the bill and executive director of Kids v. Cancer, told Focus that “there has never been a cancer study under PREA,” and noted two problems with PREA and BPCA: the fact that BPCA requirements are voluntary and often for business reasons companies elect not to undertake the studies, and time requirements on written requests mean companies complete pediatric studies too late and children end up getting treatments off label.
PREA currently says that if a company develops a drug for a certain indication, and there are pediatric populations, FDA may require certain studies. But Goodman notes that the challenge is the word “indication” has been interpreted to mean organ of tumor origin, meaning companies can avoid running certain pediatric trials.
As Nature pointed out in an editorial: “therapies that are being trialled in adults with breast cancer are exempted because children do not get that cancer, even if the drug could treat a childhood cancer in a different organ.”
Goodman also said the cost of the running the pediatric trials is not the issue for companies as they are a fraction of the cost and size of adult oncology studies. “A large Phase 2 trial for a pediatric cancer is about 250 kids,” she said.
Working with FDA and several legislators, Goodman crafted the bill, which she said she hopes will move forward like another bill she worked on that became law and established a new priority review voucher program to encourage rare pediatric drug development via a previous PDUFA reauthorization.