Dear Representatives DeGette and Bucshon,
On behalf of the Cystic Fibrosis Foundation, we write to provide input on the progress made towards the original goals of the 21st Century Cures Act and Cures 2.0 and next steps to facilitate the continued advancement of basic and clinical research and development in today’s healthcare landscape.
Cystic fibrosis is a rare genetic disease that affects nearly 40,000 people of every racial and ethnic group in the United States. In people with CF, mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in a buildup of thick mucus in multiple organ systems, leading to lung damage, life-threatening infections, and other complications. To facilitate the development of CF therapeutics — and, ultimately, a cure for CF — the CF Foundation is engaged in virtually every element of the research and development process, from preclinical discovery and identification of new therapeutics to conducting clinical trials and post-marketing surveillance.
With this experience in mind, we offer the following feedback for Representatives DeGette and Bucshon as they refine their strategies for future action and ensuring that they achieve the outcomes most beneficial to patients, the research and development field, and the health care system.
Do the policies included in Cures 2.0 that have advanced through legislation or executive action meet the needs that the original Cures 2.0 bill aimed to address?
Though the original Cures 2.0 bill did not pass through Congress, many important policies included in the legislation have advanced through other avenues. Those most relevant to the CF community have largely been achieved through executive action, including FDA guidances. The recommendations contained within published FDA guidance documents regarding multiple aspects of cell and gene therapy development, increasing use of real-world evidence and innovative clinical trial designs, improving clinical trial diversity, use of digital health technologies for drug development, and implementing decentralized clinical trials have been critical for helping both sponsors and the CF Foundation navigate a rapidly-evolving and increasingly-complex CF therapeutic development landscape.
What elements might be missing that are essential for further progress?
Combatting antimicrobial resistance
The thick, sticky mucus that clogs the lungs of people with CF traps bacteria and fungi, rendering patients extremely susceptible to colonization by life-threatening pathogens and chronic infections. As of 2023, 25% of people with CF in the United States were infected with Pseudomonas aeruginosa and 14% were infected with methicillin-resistant Staphylococcus aureus (MRSA); beyond their prevalence within, and impact on, the CF community, both multidrug-resistant Pseudomonas and MRSA have been deemed serious threats by the CDC. These and other infections can result in progressive, irreversible lung damage, increased and lengthened hospitalizations, and early death, usually due to respiratory failure. However, the frequent treatment with antimicrobial products that is required to manage these infections puts people with CF at risk for developing antimicrobial-resistant infections.
The CF Foundation appreciates the recognition in the original Cures 2.0 legislation of the growing threat of antimicrobial resistance (AMR), as reflected in the inclusion of the Pioneering Antimicrobial Subscriptions To End Upsurging Resistance (PASTEUR) Act (H.R. 2940). It is critical that the United States invest in innovative approaches to combat the AMR crisis, especially those that would incentivize the development of new antimicrobial products. The 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 you to include it in future Cures drafts and support its passage.
Improving newborn screening efforts
Given how critical newborn screening is for improving health outcomes for people with CF, the CF Foundation recommends continued inclusion of the Precision Medicine Answers for Kids Today Act (H.R. 5989, 2021), which was included in the original Cures 2.0 bill. The Precision Medicine Answers for Kids Today Act would establish a demonstration project for states to provide coverage of genetic and genomic testing for children for three years, followed by analysis of how that coverage would improve diagnosis of pediatric health conditions. It would further require the Center for Medicare and Medicaid Services to report on Medicaid coverage of genetic and genomic testing services and issue guidance for states on ways to increase coverage for children, in addition to calling for a National Academies of Sciences, Engineering, and Medicine study on impact of this guidance and the general utility of genetic and genomic testing. The CF Foundation believes that these measures will allow for more effective and comprehensive newborn screening efforts, leading to fewer misdiagnoses of children with rare and ultra-rare CFTR mutations and the resulting failure to provide timely and adequate care.
Protecting orphan drug exclusivity
Additionally, though not included in the original Cures 2.0 bill, the CF Foundation recommends including the Retaining Access and Restoring Exclusivity (RARE) Act (H.R. 7383), 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 supports the inclusion of the RARE Act in future legislation to maintain existing incentives for rare disease drug development.
Addressing coverage and reimbursement challenges for high-cost therapies, including cell and gene therapies
Given the increasing pace of approvals for gene therapies, we believe there is an urgent need for government attention to coverage and reimbursement for these treatments and a continued investment in the Center for Medicare and Medicaid Innovation (CMMI) to drive this work. The high upfront costs, limitations of clinical trial data, and patient churn across insurance markets all present significant challenges for payers when covering these therapies, which create concerns about patient access. The federal government is uniquely positioned to address some of these issues, particularly around the financial concerns and patient churn. Some markets are particularly concerning — including self-funded plans and Medicaid programs — as these payers face even greater challenges paying for these therapies and the federal government should pay particular attention to those markets. We are glad CMMI has launched the Cell and Gene Therapy Access Model to support access to curative sickle cell therapies for patients and we see great potential in supporting states as they grapple with the cost of these therapies and administrative challenges of alternative payment models. Patients need CMMI to continue this work of investing in and evaluating different financing arrangements to ensure patients have access to these costly but life-saving treatments as they come to market.
In the CF community, we are already seeing payers grapple with high-costs and as a result, putting increasingly burdensome policies in place to manage their costs. For instance, third-party entities and payers are using tactics known as maximizers, alternative funding programs, and accumulators to defray their own costs. However, these programs create confusion for patients and can lead to delays in care, higher out-of-pocket costs, and significant administrative burden. These obstacles to prescription drug access occur in a situation where patients already confront high drug prices and the practices of pharmacy benefit managers (PBMs). The promise of PBMs is that they will reduce overall system expenditures, but all too often the experience of people with CF and other life-threatening diseases is that PBM practices block or at least delay their access to specialty drugs and increase cost-sharing unexpectedly.
Congress has considered ways to reform PBM practices (at least increasing transparency of PBM operations) and address some of the payer strategies that block or hamper patient access to prescription drugs and increase cost-sharing. We encourage Congress to act to protect patient access to prescription drugs, but we realize that the legislative days in this Congress are limited and will be dedicated mostly to government spending issues. If patients do not see relief in this Congress from the access challenges described above, we urge you to make action on these issues a first priority of a third phase of delivering cures to Americans.
We applaud an effort to bring innovation to the gene and cell therapy space, as these therapies may be accompanied by difficulties in development and manufacturing, significant challenges in delivery and side effect management, coverage obstacles, and high prices. However, future Cures initiatives should at the same time include a patient-centered effort to ensure affordable access to the therapies already on the market. This might include elements of reform measures that Congress has already discussed and reviewed. We believe that you are in a unique position to advance a package of patient-focused reforms that ensure affordable access to the cures of today.
What additional reforms, support mechanisms, or incentives are needed to enhance or improve the effectiveness of the steps already taken, including any structural reform to agencies, offices, or programs involved?
As noted within this RFI, a significant number of policies included in Cures 2.0 were advanced through administrative action. In light of the recent decision in Loper Bright Enterprises v. Raimondo, Congress should take steps to ensure that the agencies responsible for implementing Cures 2.0 priorities, such as the FDA and CMS, are sufficiently empowered to continue to advance those policies. First, Congress must provide increased funding and resources to the FDA and CMS to accommodate the likely increase in staffing required to accommodate the shifting regulatory and legal landscape. In particular, agencies will need more legal regulatory expertise to ensure promulgated rules are firmly within the bounds of their statutory authority and aligned with the mission of the agency. Agencies will need more resources to conduct such analysis and without appropriate staffing, may not be able to take needed action to achieve their mandate. In addition, it is critical that future legislation be written with a level of specificity that obviates potential issues regarding statute ambiguity and agency deference.
We look forward to serving as a resource for Representatives DeGette and Bucshon as they continue to advocate for Congressional action to build a stronger research infrastructure, advance the next generation of therapeutic development, and ensure that patients have the treatments they need.