21st Century Cures Act: The next step in rare disease discovery

21st Century Cures Act: The next step in rare disease discovery

Hope for new rare disease treatments are at an all-time high, as the 21st Century Cures Act passed the US Senate on December 7, 2016.1 The bill now awaits to be signed by President Obama to be enacted as law in the United States. The passing of the 21st Century Cures Act will drastically change the way drugs are approved by the Food and Drug Administration (FDA) and will allow for faster discovery, development, and delivery of treatments.1 This creates exciting new possibilities for increasing the number of novel therapeutics for rare diseases. The bill also provides 4.8 billion dollars to the National Institutes of Health (NIH) over ten years to fund various plans that will improve care for rare disease patients such as the Precision Medicine Initiative, Brain Initiative, and Cancer Moonshot.1


“The passing of the 21st Century Cures Act will drastically change the way drugs are approved by the Food and Drug Administration (FDA) and will allow for faster discovery, development, and delivery of treatments.”

The 21st Century Cures Act will facilitate more transparency from pharmaceutical companies by making it mandatory to post their expanded access or compassionate use policies on their website.2 Expanded access refers to the use of investigational products before FDA approval and outside of clinical trials by patients with immediate life-threatening diseases or conditions who lack therapeutic alternatives.3 A study from Avalere found that only 19 percent of pharmaceutical and biotechnology companies release their expanded access policy on their websites.2 This statistic drops to 4 percent for smaller companies, making it extremely difficult for patients with rare fatal diseases to gain access to information on alternative therapeutic options.2 Companies are now granted 60 days following the official enactment of the bill to comply with the new transparency requirement. There are four main criteria that pharmaceutical companies must now meet on their websites:

  1. Contact information of manufacturers and distributors to make request for investigational product use
  2. Procedures for making an expanded access request
  3. Patient criteria for expanded access
  4. The length of time necessary for acknowledgment of receipt of expanded access request

Under the social media campaign banner of #CuresNow, hundreds of people voiced their opinions to their elected officials of how paramount the benefits of the bill would be for rare disease patients.1 The highlight of this campaign was the inclusion of the Rare Pediatric Disease Priority Review Voucher (PRV) program as part of the 21st Century Cures Act.1 Over 185 patient organizations signed a coalition letter asking Congress to renew the PRV program, which was set to expire at the end of 2016.4 This program provided incentives for pharmaceutical companies to develop drugs for rare pediatric diseases. A company that has previously received a drug approval for a rare pediatric disease may qualify for a voucher that can be redeemed to receive priority review by the FDA for a subsequent application for a different product.5 Typically, the FDA review process can take up to 18 months to receive approval. However, with the voucher, companies can cut this process down to 6 months. Not only is this a financial incentive for pharmaceutical companies, but it allows for faster delivery of cures to children who are in dire need of treatment.5 The passing of the 21st Century Cures Act means that the PRV program will receive an extension to 2020.1 The National Organization for Rare Disorders (NORD) projects that the extension of the PRV program will lead to the development of new therapies that will help more than 15 million children with rare diseases.1


“The 21st Century Cures Act will facilitate more transparency from pharmaceutical companies by making it mandatory to post their expanded access or compassionate use policies on their website.”

The 21st Century Cures Act will also introduce a bevy of changes to the FDA drug approval process by streamlining the review of genetically targeted therapies for rare diseases.1 This offers an alternative to the multiphase clinical trials for rare disease treatments. The current model of drug discovery follows the Federal Food, Drug, and Cosmetic Act passed in 1938, and involves four stages of clinical trials, a series of rigorous tests that ensures not only the cause and effect of the drug but also its safety and efficacy.6 This process costs several billion dollars, with the clinical trial phase spanning several years. The delivery of therapeutics to rare disease patients is therefore extremely slow, with very little financial incentive for pharmaceutical companies to develop these treatments.6 This may change with the passing of the 21st Century Cures Act. Companies are now able to use “surrogate endpoints” rather than the traditional hard outcome to obtain approvals.1 Biomarkers, defined as any substance that is indicative of disease, is now validated as biological evidence for clinical trials. With the recent surge in scientific knowledge and technology, doctors are now able to detect rare disease based on the presence of these biomarkers, which indicates the new possibility of diagnosing patients on a molecular level. However, the current drug approval process does not utilize this tool to its full potential. The present system uses life expectancy as its only measurement of success.7 However, the implementation of biomarkers as surrogate endpoints will decrease the period of monitoring the clinical trial participants, resulting in drastically shorter time of drug development. By characterizing the success of clinical trials based on the changes in biomarkers within patients receiving treatments, these studies can be conducted faster and much more cost-efficiently.1

Observational data that shows statistical association will now be considered during the approval process.1 Association, however, is not indicative of cause and effect and concerns have been raised by scientific experts of dangerous, lower quality drugs being distributed to patients.8 The validity of biomarkers as accurate determinants for clinical trials was also called into question and accusations have been made that the bill mainly benefits pharmaceutical companies. This highlights a difficult bioethical dilemma. On one side are experts that are stressing extreme rigor when testing for efficacy of drugs and this leads to drug approval processes spanning many years. On the other are terminally ill patients suffering from rare diseases that will not live long enough to see a cure under the current system. Navigating through the interests of multiple different groups has been extremely challenging and is one of the reasons why the 21st Century Cures Act was amended multiple times.

Nevertheless, through the efforts of more than 700 patient organizations and rare disease advocates pushing Congress to reach an agreement on the 21st Century Cures Act, the bill was reinstated on the congressional voting block after almost a year of neglect since the passing of the original bill through the house in 2015. Organizations such as NORD, Everylife Foundation for Rare Diseases, and Global Genes spearheaded multiple advocacy campaigns throughout the month of November and mobilized the rare disease community to help pass one of the biggest health reform legislations since Obamacare. Only time will tell if the 21st Century Cures Act will live up to its full potential of opening new pathways for rare disease treatment developers. New therapeutic options may be on the horizon for rare disease patients.


Works Cited:

1. Huron J. Senate Passes Landmark 21st Century Cures Act. NORD.

2. Huneycutt B. Few Manufacturers Publicly Share Policies for Granting Patient Access to Investigational Products. Avalere. http://avalere.com/expertise/life-sciences/insights/few-manufacturers-publically-share-policies-for-granting-patient-access-to. Published 2016.

3. Expanded Access. http://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/default.htm. Published 2016.

4. Coalition Letter. NORD.

5. Rare Pediatric Disease Priority Review Voucher Program (Section 529). http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm375479.htm. Published 2016.

6. Macatangay K. The Orphan Drug Act: Moving Rare Disease Research Forward. Rare Disease Review.

7. Benson NC, Daggett V. A Comparison of Multiscale Methods for the Analysis of Molecular Dynamics Simulations. J Phys Chem B. 2012;116(29):8722-8731. doi:10.1021/jp302103t.

8. Avorn J, Kesselheim AS. The 21st Century Cures Act — Will It Take Us Back in Time? N Engl J Med. 2015;372(26):2473-2475. doi:10.1056/NEJMp1506964.


Cite This Article:

Chon J., Zheng K., Chan G., Ho J. 21st Century Cures Act: The next step in rare disease discovery. Illustrated by K. Lee. Rare Disease Review. January 2017. DOI:10.13140/RG.2.2.13663.05282.

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