Representatives McCaul and Van Hollen send letters to the FDA and Teva Pharmacueticals to seek more information about the ongoing shortage of daunorubicin, an essential therapy in the treatment of leukemia in children.
BPCA and PREA Reauthorization
The House Childhood Cancer Caucus supports bipartisan efforts to reauthorize and strengthen the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA).
BPCA and PREA have been remarkably successful in ensuring that medications used in children are tested and labeled appropriately for pediatric use. As a result of BPCA and PREA, the incentives afforded to the biopharmaceutical industry to conduct appropriate drug development studies in children in large measure have succeeded, with more studies conducted over the past 10 years than likely conducted over the 5 decades prior to legislative implementation. 426 drug labels have been revised with new pediatric information and an estimated 50% of drugs used in children are now studied as compared to just 20% before the enactment of these two laws.
Despite this tremendous success, the impact of BPCA on childhood cancer drug development has been modest, and the impact of PREA has been thus far minimal. Therefore, I would like to share with you some of my observations and recommendations to strengthen BPCA and PREA for the benefit of children with cancer.
Pediatric Research Equity Act (PREA)
FDA-approved indications for almost all cancer drugs focus on the drug’s use in a specific disease, such as colon cancer, lung cancer, breast cancer, etc. PREA applies only to those drugs developed for diseases that occur in both the adult and pediatric populations. As a result, waivers can be granted for most new cancer drugs, as the common cancers observed in adults essentially do not occur in children. The key point, however, is that the molecular target of new cancer drugs may indeed be more important for childhood cancers. An example can highlight this current limitation of PREA.
Last year a new drug, crizotinib, received FDA approval for a type of lung cancer. The new drug targets a specific molecular target, called ALK. In a small proportion of patients with lung cancer, ALK has undergone a rearrangement, or a molecular change, in the tumor. The new drug is a true advancement for patients with ALK positive lung cancers. However, since lung cancers do not occur in children, there is no requirement under PREA to conduct pediatric studies.
It turns out that a subset of a very difficult to treat childhood cancer called neuroblastoma may also be dependent on ALK, though not in a manner identical to lung cancer. Although studies are underway to determine the role of crizotinib in children with neuroblastoma, there is no regulatory requirement under PREA to pursue such studies.
Part of the challenge for PREA then is that the manner in which drugs are labeled by the FDA has not yet fully caught up with the pace of science. Drugs are still primarily labeled for specific diseases. Improved PREA legislation can address this by requiring that the obligation to perform appropriate trials on children with cancer should be based on the relevance on the drug’s target to childhood cancer(s), independent of the organ, origin or name assigned to the cancer.
Recommended improvements to consider:
For an oncology drug, an assessment under Section 505B (a)(2) may be required for a pediatric oncologic indication if the molecular target of the drug for an adult oncologic indication is highly relevant to a specific pediatric cancer(s).
Best Pharmaceuticals for Children Act (BPCA)
Incentives can have a major impact on pediatric drug development. The incentive offered through BPCA, however, occurs late in the life cycle of a drug. In other words, companies have time to estimate the true value of exclusivity extensions by waiting until the drug is on the market and its market value becomes known. The real need for the childhood cancer community is to start pediatric studies at an earlier time point, which is almost always prior to drug approval for the adult indication. We recommend encouraging the FDA, based on input from the pediatric oncology research community, to issue Written Requests significantly earlier in the drug development timeline.
As work continues on BPCA and PREA reauthorization, the Caucus urges fellow lawmakers to consider the fact that childhood cancer is still the number one cause of death by disease in American children, with nearly 40 children diagnosed every day—or approximately 14,600 kids a year. It would be tragic to reauthorize BPCA and PREA without improving these two laws for children with cancer.
To read Dr. Peter Adamson, Chair of the Children's Oncology Group's, remarks for how to strengthen BPCA and PREA, as presented at the 2nd Annual Childhood Cancer Summit on Capitol Hill, please click on the link below.