Building Upon the Promise of 21st Century Cures: The Cures 2.0 Concept Paper

On April 27, 2020, US Representatives Diana DeGette (D-CO) and Fred Upton (R-MI) released a concept paper for the 21st Century Cures 2.0 (Cures 2.0) legislation. Cures 2.0 is intended to build upon the initiatives of the 21st Century Cures Act (Cures Act), enacted on December 13, 2016, and modernize the healthcare delivery system. The concept paper outlines several key areas that are intended to achieve this goal, ranging from proposals intended to spur innovation, such as further advancing the regulatory framework for digital health technologies and the use of real world data (RWD) and real world evidence (RWE) in regulatory decision making, to those regarding pandemic preparedness prompted by the ongoing coronavirus pandemic. This Advisory highlights certain proposals in the concept paper that could be most significant for drug, biologic, and device manufacturers as well as additional areas that future Cures 2.0 initiatives may address. Although the original Cures Act was enacted as freestanding legislation, the Cures 2.0 Concept Paper is particularly timely given the upcoming reauthorization of the Prescription Drug User Fee Act, which has long served as a vehicle for legislative provisions pertaining to drug and biologic development.

Background

The Cures Act, which received bipartisan support, was enacted to encourage and advance medical innovation. Among other things, the Cures Act sought to expand the types of evidence that could be used to support product approval, required the issuance of guidance on patient-centered drug development, clarified the regulatory approach to combination products and medical software, streamlined administrative processes for the National Institutes of Health (NIH) to fund medical research, and established the regenerative medicine advanced therapy (RMAT) designation to accelerate the approval of such therapies.¹

On November 22, 2019, Representatives DeGette and Upton released their initial vision for Cures 2.0 and sought additional ideas and feedback from experts and stakeholders. This initial vision contained many of the key areas contained in the concept paper, such as digital health, utilizing RWE in regulatory decision making, and modernizing product coverage and reimbursement.² The concept paper was then developed based on feedback contained in nearly 500 comments from stakeholders as well as current events.³

Cures 2.0 Concept Paper

The Cures 2.0 concept paper outlines the following six key areas of focus for this legislation: (i) pandemic health and preparedness; (ii) caregiver integration; (iii) patient engagement in healthcare decision making; (iv) diversity in clinical trials; (v) Food and Drug Administration (FDA) modernization, focusing on digital health technologies and the use of RWE; and (vi) Centers for Medicare and Medicaid Services (CMS) modernization, focusing on coverage and reimbursement.⁴

Improving US Pandemic Preparedness and Response through Support of Antimicrobial Resistance Product Commercialization

While the ongoing COVID-19 pandemic has highlighted numerous deficiencies in our systems for the development and delivery of certain medical products, a major crisis has long existed in antibiotic development and delivery. Novel antibiotics are essential in curbing the spread of drug-resistant pathogens; however, successful commercialization is often difficult. In response to recent commercial market failures of antibiotic products, Cures 2.0 would enable the Secretary of Health and Human Services (Secretary), through the Office of the Assistant Secretary for Preparedness and Response, to use certain resources and authorities to improve the commercial market for antibiotics. Under this provision, the Secretary would be required to ensure that: (i) federal support can be provided to antibiotic companies for pre- and post-market costs that may lead to bankruptcy; (ii) consideration of funding amount differentials that encourage novel antibiotics and antibiotics that address a critical need is provided; and (iii) a national strategy is implemented for preventing drug resistance in the future, which includes steps that can be taken to secure funding support from other countries and international bodies.⁵

These proposed actions would help provide additional support for antibiotic products and manufacturers and complement those that already exist. For example, under the Generating Antibiotic Incentives Now (GAIN Act), antibiotics intended to treat serious or life-threatening infections may be granted a qualified infectious disease product designation and receive a five-year exclusivity extension.⁶ In addition, the Biomedical Advanced Research and Development Authority, FDA and other federal agencies have funded research and other initiatives to support the discovery and development of antibiotics.⁷ Moreover, the Cures Act authorized the limited population pathway for antibacterial and antifungal drugs to facilitate the development and approval of drugs intended to treat serious or life-threatening infections in a limited population of patients with unmet needs.⁸

That said, it is far from clear that the Concept Paper's proposals for antibiotics are sufficient to "cure" the problems with the antibiotic market. Many believe that additional incentives—ranging from proposals for acute care antibiotic subscriptions systems, to new exclusivity frameworks, to massive rewards—will ultimately be necessary to address the ongoing antibiotic resistance crisis.

Diversity in Clinical Trials

The Cures 2.0 concept paper sets forth several policies to improve diversity in clinical trials. The first would require Medicaid to cover routine care costs of clinical trial participation for enrollees with life-threatening conditions. The second policy would require FDA to provide an update on its implementation of action items resulting from its report on clinical trial diversity mandated under section 907 of the FDASIA. Under the third policy, HHS would be required to publicize ClinicalTrials.gov and other clinical trial resources to increase awareness and understanding of clinical trials. This particular policy could help mitigate barriers to, and potentially encourage, clinical trial recruitment. Under the final policy, HHS would be required to convene a task force, consisting of NIH, FDA, academic researchers, and patient organizations, to make ClinicalTrials.gov more user- and patient-friendly.⁹

Coordinated FDA Approach on Digital Health Technologies

The Cures Act and FDA initiatives have advanced the development, revie, and approval/clearance of various digital health technologies and combination products. For example, FDA issued its Digital Health Innovation Action Plan to modify its approach in regulating digital health technologies with the goal of striking a balance between encouraging innovation and ensuring patient safety.¹⁰FDA has acted on this plan and Cures Act requirements by issuing various guidance documents, increasing its digital health staff, and initiating a Software Precertification Pilot Program to inform future regulatory models. In addition, FDA has approved and cleared products incorporating digital health technologies such as drug-device combination products and mobile medical applications. Despite these advances, FDA has acknowledged that its current authorities do not have sufficient flexibility to optimally regulate emerging technologies, particularly in the digital health space where the current regime is not well suited to the rapid cycle of innovation, design, development, and validation.¹¹

Cures 2.0 proposes to take additional steps to ensure that FDA's developing regulatory framework for digital health technologies is collaborative and inclusive of applicable FDA centers. Cures 2.0 would require the FDA Commissioner to work with the Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), and Center for Devices and Radiological Health (CDRH) to establish collaborative regulatory alignment. As part of this process, FDA would be required to set forth how the Commissioner will coordinate the work of CDER, CBER, and CDRH on digital health technology matters. It would also require FDA to issue guidance on: (i) the use of digital endpoints for regulatory review, including the validation and qualification of such endpoints and biomarkers; (ii) accepting decentralized trials, including the use of digital health technologies; and (iii) the use of digital health technologies in patient-focused product development. Notably, FDA would also be required to describe how it will coordinate with foreign regulators¹² to ensure harmonization on the regulation and use of digital health technologies.¹³

FDA Grant-Making Authority and Funding

Building upon initiatives contained in the Cures Act, Cures 2.0 would authorize funds for FDA grants in areas of innovative clinical trial design, such as complex adaptive, Bayesian, and other novel designs, and patient-focused drug development to advance science in these areas. In the context of patient-focused drug development, the concept paper advocates for prioritizing further study on clinical outcome assessment and patient experience data as well as the incorporation of digital health tools and RWD and RWE. The intent of this provision is to produce a more efficient drug development process with increased focus on real world patient needs.¹⁴

Increasing Use of RWD and RWE

The Cures Act encouraged the development and use of RWD and RWE in regulatory decision making. Among other things, the Cures Act required the Secretary to establish a program evaluating the use of RWE to support approvals of new indications for already-approved products and post-approval study requirements.¹⁵ FDA has undertaken various initiatives to fulfill these obligations, such as releasing a framework for its RWE program and several guidance documents relating to the use of RWE and RWD for product applications. To date, however, RWE has largely played a supplementary, rather than primary, role in regulatory decision making.¹⁶ Cures 2.0 proposes three policies to expedite and facilitate the promise of RWE use.

The first policy would require FDA to issue guidance on utilizing RWE in post-approval commitments for breakthrough therapy designation and accelerate approval products. Topics for such guidance would include acceptable endpoints and outcome measures, data quality standards, data transparency requirements, and study design considerations. Second, the Secretary would be required to establish a "clear and consistent" regulatory framework for the recognition and use of RWE, including outlining a framework for the collection of consistent and usable RWD and identifying how other federal agencies could use RWE.¹⁷ Finally, the Cures 2.0 Concept Paper contemplates requiring the establishment of a task force, consisting of patient groups, CMS, FDA and private sector representatives, to develop recommendations on how to encourage patients to engage in RWD generation.¹⁸

Improve FDA-CMS Communication regarding Transformative New Therapies

In an effort to ensure timely access to innovative products, Cures 2.0 would require communication between FDA and CMS for products granted breakthrough therapy designation. In particular, once a product receives this designation, FDA and CMS would commence communications that would last through post-approval collection of RWE. Through such communications, CMS would access FDA's expertise and insight when considering coverage for new products, including for purposes of "innovative coverage design intended to best take advantage of a products ability to increase care quality and reduce costs."¹⁹ This earlier communication could potentially avoid gaps between product approval and CMS coverage determinations for such products.²⁰

Breakthrough Therapy and RMAT Designations

Currently, FDA will only review requests for breakthrough therapy and RMAT designations if there is an active investigational new drug application (IND) for the product. Cures 2.0 proposes to remedy this policy so sponsors of products that otherwise meet the requirements for these designations may receive them despite not having an IND in place.²¹

Conclusion

While the concept paper describes high-level, bipartisan policies for Cures 2.0, it may take some time for legislation to develop, given competing priorities in this election year. However, in addition to shaping future legislation—whether separately enacted or part of the next PDUFA reauthorization—these insights into proposed initiatives for Cures 2.0 may help inform current FDA policy and enable drug, biologic and device manufacturers to evaluate long-term strategies and initiatives.

© Arnold & Porter Kaye Scholer LLP 2020 All Rights Reserved. This Advisory is intended to be a general summary of the law and does not constitute legal advice. You should consult with counsel to determine applicable legal requirements in a specific fact situation.