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An updated version of legislation to modernize clinical research policies and FDA expedited approval pathways is circulating on Capitol Hill in anticipation of gaining approval in the coming year. The latest “Cures 2.0” draft released by Reps. Diana DeGette (D-Col) and Fred Upton (R-Mich) also supports the creation of the Biden administration’s proposed Advanced Research Projects Agency for Health (ARPA-H) to accelerate research on cures for devastating diseases such as cancer, diabetes, Alzheimer’s and more.
The proposal builds on the initial 21st Century Cures legislation, which was developed on a bipartisan basis by DeGette and Upton in 2015 and aims to further improve how new critical treatments are tested and delivered to patients. The Cures 2.0 measure has been under discussion for several years and currently is in the form of a “discussion draft” that is open to revision and addition by fellow lawmakers.1 A final measure could be included in upcoming federal budget legislation or in the bill needed in 2022 to reauthorize FDA user fee programs.
Provisions in the current draft address interest in advancing diversity in clinical trials, expanding digital health, further utilizing real world evidence (RWE) in clinical trials and postapproval studies, and enhancing FDA oversight of cell and gene therapies. There are grants to support novel clinical trial designs and other drug development innovations, but many provisions merely instruct FDA to issue reports or participate on advisory panels, without making significant policy changes. And under the “something-for-everyone” approach, the legislation would provide $25 billion to support research at independent institutions, universities and public laboratories to “continue their work on thousands of federally-backed projects.”
A section that may gain more attention aims to facilitate the completion of post-approval studies for new drugs granted accelerated approval. The approach here is to authorize broader use of clinical evidence, patient registries and other sources of RWE to satisfy post-marketing commitments, a policy already in effect for regenerative medicine advanced therapy (RMAT) products. But the ongoing controversy over FDA’s recent accelerated approval of Biogen’s Alzheimer’s drug has raised concern about the timing and scope of evidence to confirm the benefits of this very expensive drug with uncertain health gains, and this provision is likely to be expanded to consider broader accelerated approval issues.
The draft bill also addresses the need for manufacturing information to advance expedited development and review of breakthrough drugs, particularly cell and gene therapies. The legislators call for FDA to publish new guidance on standards and data on chemistry, manufacturing and controls (CMC) to support such applications. The sense is that FDA already has provided much guidance on what clinical safety and efficacy testing is required for innovative products, but a remaining barrier to expedited approvals may arise from uncertainty over what CMC information is needed during development and for initial approval, and what can be provided postapproval. Draft guidance is due in six months and should consider the benefits of requiring more manufacturing information early compared to risks of delaying patient access to a needed treatment.
More controversial is a proposal supporting the establishment of additional FDA Centers of Excellence. The success of the agency’s Oncology Center ofExcellence (OCE) to shepherd promising, though risky, cancer treatments through product development, testing and approval has spurred interest among a range of patient disease groups to gain similar priority treatment for new therapies for rare diseases and neurological conditions, among others. However, FDA officials are not enthusiastic about siphoning off resources for additional centers, and OCE director Richard Pazdur recently emphasized the need for a clear scientific basis plus added resources to actually advance R&D through such entities.
The broader Cures bill also looks to advance public health by expanding diagnostic testing, vaccine development and preparedness for future pandemics. A more immediate need is to identify individuals with “long COVID” in order to ensure care of these patients and to further medical research on diagnostics and therapeutics in this area. The measure supports establishing a national testing and response strategy for future disease outbreaks, with programs to help rare disease patients deal with public health emergencies and to educate all Americans on the importance of vaccines and immunization programs.
This section of the bill also includes the proposed PASTUER (Pioneering Antimicrobial Subscriptions to End Upsurging Resistance) Act, which supports R&D for new antibiotics with specifics to prevent antimicrobial resistance (AMR).2 The measure would authorize a “subscription model” for government payment for new antibiotics to ensure return on investment to drug developers despite limiting drug use to the most seriously ill patients to avoid AMR.
Added Cures 2.0 measures fall under the heading of support for patients and caregivers. The bill backs education and training for caregivers and provides support for patients navigating health information systems. FDA will improve diversity in clinical trials, while the Government Accountability Office (GAO) studies barriers to clinical trial participation. And drug manufacturers will be required to collect and report on patient experience in clinical trials, while Medicare expands coverage of costs for individuals participating in certain clinical studies. Another GAO study would recommend ways for Medicare to cover innovative health technologies. Medicare also will examine programs to extend telehealth services and to provide coverage for breakthrough medical devices and for precision medicine.
Some of these initiatives could be addressed by ARPA-H, which would be located at the National Institutes of Health (NIH) with the charge of speeding “transformational innovation in health research.” Specific projects would create new technological and disease models, support high-risk exploration, offer financial incentives for certain critical solutions, and complement NIH and private sector research initiatives.