Other Drug Development Policies of Give Kids a Chance Act
Policy formerly known as:
Innovation in Pediatric Drugs Act
Children are not just small adults. Drugs work differently in children and must be studied specifically for their use. Yet too often, drug development still leaves children behind. Section 2 of the Give Kids a Chance Act, the Innovation in Pediatric Drugs Act will help speed therapies to children who need them—including children with pediatric cancer and other rare diseases—by making needed changes to the pediatric drug laws.
PEDIATRIC DRUG LAWS: AN OVERVIEW
The Innovation in Pediatric Drugs Act would make needed improvements to the Pediatric Research Equity Act (PREA), a law that requires the study of drugs in children. Data resultng from PREA studies are added to drug labels to give parents and providers essential information on the safety and efficacy of drugs used in children. PREA requires drug companies to study adult drug indications in children when children could benefit from pediatric studies.
In 2017, the Research to Accelerate Cures and Equity (RACE) for Children Act amended PREA so that FDA could require companies to conduct pediatric studies of new adult cancer therapies whose molecular targets are relevant to pediatric cancers. Prior to 2017, PREA in effect excluded most oncology drugs from pediatric testng because cancers were understood by their location in the body.
THE INNOVATION IN PEDIATRIC DRUGS ACT: Ensuring Drugs for Rare Diseases are Studied in Children
Providing Equal Accountability for Pediatric Study Requirements
Due dates for PREA studies are typically deferred by FDA until a date after the approval of the drug for adults. Unfortunately, FDA has no effective enforcement tools to ensure that these studies actually get completed on time—or at all. Congress tried to solve this problem in 2012. It allowed FDA to send “non-compliance letters” to companies that failed to complete their pediatric studies. Disappointingly, this did not fix the problem. According to an analysis conducted by the American Academy of Pediatrics, as of early 2021, 123 PREA non-compliance letters had been issued, yet only 41 (33%) of these instances of non-compliance had been resolved. That lead to 82 (67%) instances of non-compliance unresolved with studies still late. The average late study was 4.4 years late. Twenty-one studies were between 5-10 years late, 7 were 10-15 years late, and 3 were more than 15 years late.
FDA requirements for postmarket studies in adults can be effectively enforced, but requirements for postmarket studies in children cannot.
If a company fails to complete adult postmarket studies, FDA can penalize the company by imposing a fine but it is prohibited, by law, from applying those penalties to pediatric postmarket studies under PREA. If FDA is not given additional enforcement tools, not only will these studies required in the past not get completed, but future studies will be in jeopardy too, including pediatric cancer studies required under the RACE for Children Act, which went into effect in 2020.
The Innovation in Pediatric Drugs Act would amend PREA to give FDA the authority it needs to ensure that legally required pediatric studies are completed in a timely way.
Investing in Pediatric Studies of Older Off-Patent Drugs
The FDA incentives and requirements under BPCA and PREA work for many newer drugs, but unfortunately cannot help encourage studies of older drugs. For this reason, Congress in 2002 authorized a BPCA program at the National Institutes of Health. This program funds NIH to do studies of off-patent drugs used in children that companies cannot be incentivized or required to conduct. To date, 18 pediatric drug labels have been changed through this program. The BPCA NIH program has been flat-funded at $25 million since its original authorization in 2002. Drug studies are expensive and while the program is an efficient use of scare resources, the $25 million funding level is insufficient to meet the current needs. When accounting for biomedical research inflation, the purchasing power of the program in 2022 was only 56% of what it was in 2002.
The Innovation in Pediatric Drugs Act would provide that of the amount made available for pediatric research to each national research institute and national center for fiscal years 2025, 2026, and 2027, the Director of NIH is authorized to make available up to one percent of such amount for pediatric clinical trials pursuant to BPCA.
Policy formerly known as:
The RARE Act
Introduced by Senators Tammy Baldwin and Mike Braun, and by Representative Doris Matsui
Bipartisan legislation that would respond to the 11th Circuit Court’s decision in Catalyst Pharms., Inc. v. Becerra and preserve access to treatments for rare disease patients
The Orphan Drug Act (ODA) of 1983 was enacted to provide incentives to support research and development into drugs for rare diseases with small patient populations. The law established a
two part process for obtaining orphan drug status: (1) at an early stage in the drug development process, a company can request that FDA “designate” the drug as an orphan drug to prevent, diagnose or treat a rare disease or condition, which allows the company to receive tax credits for the research and clinical testing on the drug; (2) after completing the necessary clinical studies and obtaining FDA approval, the drug is then awarded seven years of “orphan drug exclusivity” that protects the specific use of the drug that is approved.
For example, a drug sponsor could get a drug designated for “treatment of pulmonary arterial hypertension” but ultimately the drug is only FDA approved for use in a smaller patient population (i.e., adults over age 30 with pulmonary arterial hypertension). FDA has long construed the ODA and regulations to mean that the orphan drug exclusivity protects only the approved use of the drug, not the rare disease for which the drug was designated. Unfortunately, the 11th Circuit decision would turn this decades-long practice on its head.
Background on 11th Circuit Case: The drug company Catalyst has an approved drug product granted orphan drug designation for its use in adult patients with a rare disease called Lambert- Eaton myasthenic syndrome, or LEMS. FDA’s regulations have long interpreted the scope of orphan drug exclusivity (ODE) to be limited to the use or indication within the designated rare disease for which the drug is approved, meaning the agency would not block approval of the same drug from a different manufacturer for different uses or indications, even if it sought to treat the same rare disease or condition. A different drug maker, Jacobus, studied the same drug for use in children, and provided dosing and administration information for this specific population. Jacobus then applied for and obtained approval of its drug for use only in children with LEMS. In keeping with its longstanding practice, FDA determined Jacobus’s drug for children was not blocked by Catalyst’s orphan drug exclusivity for their drug for adults. Catalyst then sued FDA, arguing that the scope of ODE should block FDA from approving another sponsor’s application for the same drug for all other uses or indications, even though Catalyst’s drug was only approved for adults.
On September 30, 2021, the U.S. Court of Appeals for the 11th Circuit issued its decision in Catalyst Pharms., Inc. v. Becerra, and ruled in favor of Catalyst, holding that under the plain language meaning of the Federal Food, Drug, and Cosmetic Act, orphan drug exclusivity blocks approval of the same drug for the entire disease or condition for which the drug is granted orphan-drug designation, regardless of whether the drug was approved and found to be safe and effective only for a narrower use or indication, such as only an adult population.
As a result of this decision, FDA was forced to withdraw marketing approval for the Jacobus drug, the only approved treatment option for children.
What this means: The court’s decision in Catalyst has far-reaching, adverse impacts, especially for children with rare diseases. Without a fix, drug companies are incentivized to seek the broadest orphan drug designation as possible and then focus clinical studies only on the narrowest patient populations that would support approval. In so doing, companies could then rely on the broader designated orphan disease and block approval for any different uses or other patient populations.
The Retaining Access and Restoring Exclusivity (RARE) Act would codify FDA’s longstanding interpretation of the Orphan Drug Act to ensure that the scope of the orphan drug exclusivity in Sec. 527 of the Food, Drug and Cosmetic Act is clarified to apply only to the same approved use or indication within such rare disease or condition instead of the same disease or condition. This would give FDA the necessary authority to approve the same drug from different manufacturers if they aim to serve different patient populations and combat manufacturers’ efforts to take advantage of the Court’s ruling in Catalyst.