The 21st Century Cures Act commits substantial amounts of federal funding to key biomedical initiatives and provides expedited approval pathways for certain drugs and medical devices.
Implications | The new law makes major contributions to the pharmaceutical industry, including expedited regulatory pathways for certain antimicrobials in limited populations, use of real-world evidence in regulatory submissions for expanded indications of marketed drugs, and expanded use of patient input in FDA decision-making. |
Outlook | The signing of the 21st Century Cures Act into law is certainly a major victory for the biopharmaceutical and medical devices industries, as the legislation is anticipated to notably modernise and reform certain regulatory pathways and shorten time to market. |
President Barack Obama has signed into law the long-awaited bipartisan bill that will probably reshape the research and development landscape in the United States following its overwhelming approval by Congress. The 21st Century Cures Act earmarks substantial amounts of federal funding to key biomedical initiatives under the National Institutes of Health (NIH), including USD1.5 billion for Precision Medicine, USD1.5 billion for Brain Research Through Advancing Innovative Neurotechnologies (BRAIN), and USD1.8 billion for the Cancer Moonshot initiative, all established under Obama's presidency. The law also allocates USD1 billion to the states over two years to help tackle opioid abuse and addiction, and provides support to mental health initiatives. However, most notable are the changes and updates that it makes to accelerate certain FDA regulatory pathways for pharmaceuticals and medical devices.
Around 58 pharmaceutical companies, 26 biotechnology companies, and 24 medical device companies spent more than USD192 million in lobbying efforts on the bill among other legislative efforts, according to Kaiser Health News. Major contributions of the law to the pharmaceutical industry include:
- Limited population pathway: Establishment of a "limited population" antimicrobial drug pathway, for the expedited approval of new antibiotics and other anti-infectives for use in patients with significantly unmet medical needs before the availability of safety and efficacy studies in these specific populations. The label would include "Limited Population" along with the proprietary name of the drug.
- Real-world evidence: Allows the use of "real-world" data for regulatory submissions, including expanded indications for marketed drugs.
- Accelerated approval for regenerative advanced therapies: Establishment of a pathway for expedited approval of regenerative therapies based on surrogate endpoints, such as tumour shrinkage, rather than just clinical outcomes or overall survival.
- Reauthorisation of PRV programme: Renewal of the rare paediatric disease priority review voucher (PRV) programme that the FDA was not in favour of keeping until 2020.
- Expanded access policy: Requires pharmaceutical companies interested in providing expanded access to provide publicly available compassionate use policies to allow patients to use unapproved drugs outside of clinical trials.
- Qualification of drug development tools: Required the FDA to make a public list of the development tools and surrogate endpoints that qualify for drug approval under the Drug Development Tools Qualification Programme in order to facilitate use of new biomarkers, patient-reported outcomes, and animal models in drug development.
- Patient-focused drug development guidance: Requires the FDA to issue guidelines regarding collection of patient experience data.
- Patient experience data: Allows the incorporation of patient perspectives in the FDA approval process for drugs and medical devices.
Real-world evidence
One of the more controversial provisions in the law established an FDA regulatory framework for the use of "real-world evidence" for regulatory approval of certain drugs. Leading up to the approval of the Cures Act, and ahead of the reauthorisation of the Prescription Drug User Fee Act (PDUFA) for fiscal years 2018 through to 2022, FDA commissioner Robert Califf along with 14 other FDA staff members issued a statement in the New England Journal of Medicine recommending caution concerning the use of real-world data "derived from multiple sources outside typical clinical research settings", including electronic health records, claims records, product and disease registries, as well as data obtained from personal device and health applications. The use of this information could lead to "flawed conclusions", according to the article, and work needs to be done to provide rigorous methods for data collection and analysis. The risk is particularly notable in fields of precision molecular medicine and for orphan drugs, many of which are anticipated to be reviewed under accelerated approval programmes.
Funding for the NIH and FDA
Although the new NIH initiatives strongly benefit from the new law, the amendments to the bill have cut the previously allocated funds (USD8.75 billion) to the NIH by half. Furthermore, the USD4.8 billion now allocated to the NIH over 10 years is not guaranteed, and needs to be approved by Congress annually. The new law will allocate USD500 million to the FDA over the next 10 years, but this was criticised as being barely enough to cover the additional workload created for the agency by the Cures Act.
Furthermore, in order to provide the extra funding for the NIH initiatives, the law has cut USD3.5 billion or 30% of the Prevention and Public Health Fund established under the Affordable Care Act to help prevention of Alzheimer's disease, hospital-acquired infections, and chronic illnesses, among others. Meanwhile, the National Alopecia Areata Foundation also faces a setback despite USD40,000 spent on lobbying efforts after provisions in the law exclude hair-growth drugs from the Medicaid programme.
Outlook and implications
The signing of the 21st Century Cures Act into law is certainly a major victory for the biopharmaceutical and medical devices industries, as the legislation is anticipated to notably modernise and reform certain regulatory pathways and shorten time to market. This in turn is anticipated to save drug and medical device manufacturers billions of dollars. It is no surprise that certain provisions in the law remain somewhat controversial; considered a "handout" to the pharmaceutical industry by certain advocacy groups, including Public Citizen, the National Physicians Alliance, and the National Center for Health Research. They have raised concerns regarding expedited approval of potentially unsafe drugs and devices, allowing pharmaceutical companies to promote drugs for off-label use to insurers, and not addressing the issue of escalating drug costs. Many opponents of the new law have warned that it substantially reduces the FDA's authority to regulate drugs and diminishes the reliance on randomised clinical trials, considered the gold standard for determining drug safety and efficacy.
The use of real-world evidence in FDA approval pathways is certainly a significant milestone for the pharmaceutical industry, and one that will probably save drug manufacturers substantial time and money. However, the FDA has already warned that despite the important role this new data can play in regulatory submissions, "caution is still needed, and expectations of 'quick wins' resulting from the use of such evidence should be tempered accordingly".