Sweeping Changes to Drug and Device Regulation Proposed Via Bipartisan Legislation

Representatives Diana DeGette (D, Colorado) and Fred Upton (R, Michigan) recently released a

Title I: Putting Patients First by Incorporating Their Perspectives Into the Regulatory Process and Addressing Unmet Needs

Title II: Building the Foundation for 21st Century Medicine, Including Helping Young Scientists

Title III: Modernizing Clinical Trials

Title IV: Accelerating the Discovery, Development, and Delivery Cycle and Continuing 21st Century Innovation at NIH, FDA, CDC, And CMS

Title V: Modernizing Medical Product Regulation

Representatives Diana DeGette (D, Colorado) and Fred Upton (R, Michigan) recently released a "discussion draft" of the 21st Century Cures Act.¹The stated intent of the almost 400-page bipartisan bill is to "accelerate the discovery, development, and delivery of 21st century cures." The bill is subdivided into 5 major areas (see below).One of the major goals of the bill is to modernize clinical trial research for drugs and medical devices.¹This includes providing clearer instructions for the role of institutional review boards, streamlining and standardizing regulatory requirements for research involving human subjects, and allowing clinical trial sponsors more leeway in trial methodology. Under the Century Cures Act, the US Food and Drug Administration (FDA) would have to consider trial sponsor’s requests to use adaptive trial designs, Bayesian trial models, nonstandard surrogate endpoints, or different statistical methods for data analyses.

In oncology, the FDA has already shown its willingness to accept surrogate endpoints. For example, the FDA has approved several cancer drugs based on their ability to improve progression-free survival (PFS) or shrink tumors. According to a 2014Milwaukee Journalinvestigative report, 74% of the 54 cancer drugs approved in the past decade were approved despite no clinical trial evidence of improvement in overall survival.²Using surrogate endpoints has the potential to reduce the size and expense of a clinical trial, but some researchers criticize the approach. They say approving a drug based on a surrogate endpoint whose clinical meaningfulness is unclear should be questioned given the skyrocketing costs of many new cancer drugs.^2,3

Under the proposed legislation, biomarkers could also be used as a measure of response and serve as surrogate endpoints to overall survival.¹A "requestor" will be able to petition the Department of Health and Human Services (HHS) to propose a biomarker for consideration. The bill requires HHS to convene a public forum to discuss the biomarker proposal and permits the requestor to appeal any adverse decision.

A major change implemented through the Century Cures Act would be in how the FDA is allowed to consider breakthrough therapies. Currently, the FDA may rely on promising preliminary data of efficacy to designate a drug as a breakthrough therapy, which provides the sponsor with additional support in an effort to expedite the approval process. The proposed legislation permits the FDA to approve a breakthrough therapy based on early clinical data of safety and efficacy and then require postmarketing assessments. One concern with this is whether or not companies will comply with required postmarketing study. In 2012, the FDA reported that many companies who agreed to carry out postmarketing studies as part of obtaining approval failed to do so or did a substandard job.⁴

One important benefit of the legislation for patients is its emphasis on fostering greater involvement of patients in the drug development process. This is something the FDA has already started to implement.¹The FDA regularly holds meetings on drug development in various diseases, including cancer, with patients and patient advocacy groups. The goal is to take "patient experience data" into consideration when evaluating the risks and benefits of a new therapy. Another possible benefit of the bill is a requirement that makers of any drug given a breakthrough, fast track, or Qualified Infectious Disease Product Designation establish a corporate policy to make the drug available for compassionate use.

Of possible benefit to Medicare patients, particularly those who live in rural areas, are provisions of the proposed law that would expand access to telemedicine. Under the Century Cares Act, the Centers for Medicare & Medicaid Services would be required to provide coverage for telehealth services and to reimburse visits conducted via a telecommunications system at the same rate as an in-person visit.¹

The proposed law also has what some might view as a few gifts to the pharmaceutical industry. The Century Cares Act calls for the FDA to revise its policies for how companies may use social media to promote their products.¹Under the law, the FDA would have to allow companies to use condensed language about a drug, for example in a Tweet or Facebook post, as long as they include a hyperlink to the complete information. And in what may become some of the most contested provisions, the Century Cares Act extends the exclusivity period for certain new drugs by 2 years and for orphan drugs by 6 months. It also grants some exclusivity to US manufacturers of generic drugs and devices. During his tenure, President Obama has unsuccessfully fought to have the exclusivity for new biologics and other drugs reduced in the belief that it will spur competition and reduce prices. Supporters of longer exclusivity periods, however, argue that these longer timelines provide more incentive for new drug development.

The bill is still in draft form, and the final form will likely look very different from what has been published.¹It is also a very long bill, and it will take the media and other interested parties time to explore all the nuances of the proposed legislation. AtTargeted Oncology, we will do our best to keep readers updated on any new developments that arise with the 21st Century Cures Act.

References

1. Discussion document: 21st Century Cures Act. http://energycommerce.house.gov/sites/republicans.energycommerce.house.gov/files/114/Analysis/Cures/20150127-Cures-Discussion-Document.pdf. Published January 2015. Accessed February 5, 2015.
2. Fauber J, Chu E. FDA approves cancer drugs without proof they're extending lives. Milwaukee Journal. http://www.jsonline.com/watchdog/watchdogreports/fda-approves-cancer-drugs-without-proof-theyre-extending-lives-b99348000z1-280437692.html. Published October 26, 2014. Accessed February 6, 2015.
3. Booth CM, Eisenhaur EA. Progression-free survival: meaningful or simply measureable?J Clin Oncol. 2012;30:1030-1033.
4. US Food and Drug Administration. Report on the performance of drug and biologics firms in conducting postmarketing requirements and commitments; availability. https://www.federalregister.gov/articles/2012/03/06/2012-5302/report-on-the-performance-of-drug-and-biologics-firms-in-conducting-postmarketing-requirements-and#p-10. Published March 6, 2012. Accessed February 6, 2015.
5. Patient-focused drug development: disease area meetings planned for fiscal years 2013-2015. http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm347317.htm. Updated February 5, 2015. Accessed February 6, 2015.