Dear Chair Guthrie and Ranking Member Eshoo,
On behalf of the Cystic Fibrosis Foundation, we thank the House Energy and Commerce Health Subcommittee for its dedication to supporting patients with rare diseases, including the nearly 40,000 children and adults living with cystic fibrosis in the United States. CF is a complex, multi-system genetic disease that can affect people of every racial and ethnic group. It causes the body to produce thick, sticky mucus that clogs the lungs and digestive system and can result in life-threatening infections; if left untreated, these infections and other exacerbations caused by CF can result in irreversible lung damage and early death, usually due to respiratory failure.
The CF Foundation is a national organization dedicated to ensuring that people with CF live long, fulfilling lives, with the ultimate goal of curing CF. We achieve this by investing in research and development of new CF therapies, advocating for access to care for people with CF, and funding an accredited network of specialized CF care centers. In response to the hearing on legislative proposals to support patients with rare diseases, the CF Foundation offers support for several pieces of legislation tackling antimicrobial resistance (AMR), orphan drug exclusivity, patient-focused drug development, and access to specialized care across state lines — topics that are critical to the CF community. In addition to the bills slated for discussion, the CF Foundation also urges the Committee to take up and pass H.R. 2940, the Pioneering Antimicrobial Subscriptions To End Upsurging Resistance (PASTEUR) Act.
Combating the Threat of Antimicrobial Resistance:
AMR poses a rapidly-growing threat to both CF patients and the entire United States population. According to the 2019 CDC Antibiotic Resistance Threats in the United States report, AMR causes 2.8 million infections and claims over 35,000 lives in the United States each year. The COVID-19 pandemic only worsened this crisis: in 2020, the U.S. experienced a 15% increase in hospital-onset AMR infections and deaths, and experts do not expect a return to pre-pandemic levels without concerted action. The economic toll of the AMR crisis is also staggering: according to a 2022 report from the National Academies of Sciences, Engineering, and Medicine, the direct medical costs in the U.S. of treating only six of the most common drug-resistant pathogens is $4.6 billion per year. Notably, this figure does not include associated and downstream costs, including the cost to the health system after discharge, lost wages, diminished worker productivity, short- and long-term disability, mortality, and cost burden on family and caregivers.
The AMR threat is particularly dangerous for people with CF, who are extremely vulnerable to pathogenic colonization and life-threatening infections due to the thick, sticky mucus in their lungs. These infections often require hospitalization and treatment with antimicrobials and can lead to losses in lung function and death. For these reasons, the CF Foundation both supports the Antimicrobial Resistance Research Assessment Act and strongly urges Congress to pass H.R. 2940, the Pioneering Antimicrobial Subscriptions To End Upsurging Resistance (PASTEUR) Act.
The H.R. 7436 Antimicrobial Resistance Research Assessment Act, which directs the United States Government Accountability Office (GAO) to prepare an exhaustive report on federal efforts to address AMR, including the identification of and proposed recommendations for duplicative efforts, will help ensure efficient use of federal resources in the effort to address AMR. Given its magnitude and complexity, tackling the AMR crisis requires a multi-faceted approach. This includes the establishment and operation of task forces, committees, and programs; funding antimicrobial research and development; expanding national, regional, and state capacity for AMR surveillance, detection, containment, and prevention; and numerous other approaches. However, due to the scope, volume, and inter- and multi-agency nature of these AMR programs, it is important to ensure that government resources are utilized in the most efficient manner possible and not allocated to duplicative efforts and the CF Foundation supports a GAO review of these programs. Furthermore, as an organization at the forefront of research and development for phage therapies, the CF Foundation supports a more extensive characterization of current federal phage therapy programs.
In addition to establishing a comprehensive overview of existing federal AMR efforts, is also critical that the United States invest in innovative approaches to combating the AMR crisis, especially those that would incentivize the development of new antimicrobial products. H.R. 2940, the Pioneering Antimicrobial Subscriptions To End Upsurging Resistance (PASTEUR) Act offers an innovative post-market incentive structure to both facilitate the revitalization of the antimicrobial pipeline and make novel antimicrobials available to those in need. Despite the magnitude of the AMR crisis, the antimicrobial ecosystem is remarkably weak. Fewer than 50 antibacterial therapeutics are currently in clinical development worldwide, only a handful of which are for the most threatening gram-negative pathogens. In recognition of the dire unmet need for innovative antimicrobial products, the GAO formally recommended in a March 2020 report that the Department of Health and Human Services develop a strategy to further incentivize the development of new antimicrobial products for drug-resistant infections, including through the use of post-market financial incentives.
Under PASTEUR’s subscription model, the federal government can enter into contracts with developers of innovative antimicrobials to pay for a reliable supply of product. Payments are decoupled from the volume of antimicrobials used, thereby removing the incentive for companies to promote the widespread use that often results in the development of drug-resistant pathogens. Critically, PASTEUR contracts are awarded exclusively on the basis of innovation and success. PASTEUR will only fund antimicrobials that have been approved by the FDA and meet established criteria for novelty and fulfilling unmet AMR needs — in other words, products with a significant impact on patients and public health. Furthermore, the subscription contract is all-inclusive, and the federal government only pays once. Economic modeling performed by the Center for Global Development suggests that this sort of subscription-based approach to incentivizing antimicrobial development would generate a significant return on investment in both the short- and long-term. From the U.S. domestic perspective, taking into consideration the value of averted death and disease plus associated hospital costs, the predicted ROI for an annual $1 billion investment in new, high-impact antimicrobials was calculated at 6:1 over ten years and 28:1 over thirty years.
Without innovative, cost-effective strategies for tackling the AMR crisis, the tremendous impact of AMR on people with CF and the broader United States population will continue to worsen. Because the PASTEUR Act presents an opportunity to strengthen the incredibly weak antimicrobial research and development pipeline, stabilize the broken market for antimicrobial products, and ensure that patients have access to the novel treatment options they need, the CF Foundation urges Congress support its passage.
Protecting Orphan Drug Exclusivity:
The CF Foundation also supports H.R. 7383, the Retaining Access and Restoring Exclusivity (RARE) Act, which would restore the FDA’s long-standing system for awarding orphan drug exclusivity (ODE) based on “use or indication” within a disease or condition. To incentivize the development of drugs for rare and orphan diseases, the Orphan Drug Act established a term of market exclusivity for drugs intended to treat those populations. ODE protects companies from parties seeking approval for the “same drug for the same disease or condition” for seven years. Importantly, the FDA has historically interpreted this as protecting exclusivity for the “same use or indication” within a disease or condition. However, the Catalyst Pharms., Inc. v. Becerra court decision would require the FDA to grant ODE based on “disease or condition,” not “approved use or indication” within the disease or condition. Under the Catalyst decision, once an orphan drug is approved for a single use or indication, the FDA cannot approve another company’s application for the same drug for any additional use or indication within that disease (e.g., pediatric populations).
In the case of CF therapeutics, sponsors often pursue label expansions to add additional indications, such as new genotypes or age groups, to a drug’s label. Each label expansion receives an additional, but separate orphan drug exclusivity period. Without the clarification provided by the RARE Act, these additional label expansions could block generic drugs from coming to market for the populations included in previous labels, even when those earlier exclusivity periods expire. This means that patients may wait longer for more affordable options. The CF Foundation therefore asks Congress to support the RARE Act and restore FDA’s long-standing policy on orphan drug exclusivity.
The CF Foundation appreciates the opportunity to support and provide feedback on the subcommittee’s critical efforts to improve the lives of rare disease patients. We look forward to continuing this dialogue and serving as a resource for the committee going forward.