The narrative for 21st Century Cures Act stemmed from a political spotlight on two girls with no treatment for their rare diseases, as presented by Senator Upton in his opening statement at the Legislative Hearing on 21st Century Cures Act. Their story represented a larger public health issue - that there exist 10,000 known diseases, only 500 of which have treatments, and 7,000 of which are considered rare diseases. The Cures Act contains several provisions aimed at advancing new drug therapies including those for rare disease.

Rare diseases are often serious and difficult to diagnose, many affect children and close to 95 percent of rare diseases lack treatment. The earlier Orphan Drug Act of 1983 created various incentives for sponsors to develop treatments for rare disease. To be designated as an orphan drug and receive these incentives, a sponsor has to demonstrate that the disease or condition for which the drug is intended meets one of the criteria below:

  1. It affects fewer than 200,000 people in the United States.
  2. If the drug is a vaccine, diagnostic drug or preventive drug, it will be administered in the United States to fewer than 200,000 people per year.
  3. For drugs described in A or B, there is no reasonable expectation that costs of research and development of the drug for the indication can be recovered by sales of the drug in the United States.

Specifically, the Cures Act under Subtitle B - Advancing New Drug Therapies further addresses the unmet need of development of treatments for rare diseases.

3012. Targeted Drugs for Rare Disease

Section 3012 of the Act clarifies the authority of the FDA with regard to genetically targeted drugs for rare diseases. The Cures Act helps to advance these therapies by allowing sponsors of genetically targeted technology or variant protein targeted drugs to rely on data for the same or similar technology from previously approved applications by the same sponsor (or another sponsor when given right of reference to this data).

A genetically targeted drug modulates the function of the gene or its associated product. Under the added language in the Act, genetically targeted technology is clarified to mean a technology comprising non-replicating nucleic acid or analogous compounds with a common or similar chemistry that is intended to treat one or more patient subgroups, including subgroups of patients with different mutations of a gene, with the same disease or condition, including a disease or condition due to other variants in the same gene. A variant protein targeted drug modulates the function of a product of a mutated gene where the mutation is responsible in whole or in part for a given disease or condition; and is intended to treat one or more patient subgroups, including those with different mutations of a gene with the same disease or condition. Targeted drugs accounted for a large percentage of orphan drug approvals (60 percent of orphan drug approvals in 2013 vs. 20 percent of non-orphan approvals). One example of a targeted drug is KALYDECO® (ivacaftor), approved in 2012, for treatment for a rare form of cystic fibrosis (CF), targeting a specific genetic mutation in a subset of CF patients.

3013. Reauthorization of Program to Encourage Treatments for Rare Pediatric Diseases

Section 3013 of the Act extends the incentive program previously enabled by the FDA Safety and Innovation Act (FDASIA) by reauthorizing the pediatric rare disease priority review voucher program until 2020. (Drugs designated prior to October 1, 2020 will continue to receive a voucher if approved before October 1, 2022.) Under this program, if a drug qualifies for a priority review, the sponsor will receive a unique pediatric review voucher at the time of drug approval. A sponsor can apply this review voucher to a different drug in the future to seek priority review, which has a four-month shorter review clock than a standard marketing application. Also, it allows for the drug company to sell this voucher to others if it does not want to make use of it, with no limit to how many times the voucher can be sold and resold. The pediatric voucher program also allows for product to be designated early on during the IND stage (which could potentially incentivize early stage investors) or could be requested at a later stage. The first orphan drug to have used this pediatric rare disease voucher was elosulfase alfa (VIMIZIM®) approved in 2014. VIMIZIM® is an enzyme replacement drug for the treatment of Morquio syndrome which affects approximately 800 people in the U.S.

3014. Government Accountability Office (GAO) Study of Priority Review Voucher Programs

Priority review vouchers were established to incentivize companies to develop drugs for neglected tropical disease, rare pediatric disease (2012) and medical countermeasures. However, this rare disease voucher program is considered somewhat controversial as to whether it is an effective incentive to develop drugs for rare pediatric diseases, according to FDA officials. A voucher entitles a sponsor to a six-month priority review by FDA rather than the 10-month standard review, regardless of whether the drug would meet the requirements for a priority review. GAO published a congressional study in March 2016 that concluded it was too early to gauge effectiveness of FDA’s pediatric voucher program.

The new provision under the Cures Act allows the GAO to assess all priority review voucher programs (neglected tropical diseases, rare pediatric diseases and medical countermeasures) for effectiveness and their overall impact. Studies will include an analysis of drugs awarded a specific voucher, including the indications under which the drug is approved, the extent to which the voucher incentivized drug development and the impact of the drug in addressing the goals of the specific program. The studies will also include a review of the specific programs by assessing resources used by FDA in executing priority review and the effect on products that did not qualify for priority review, estimating the value of the voucher, and reevaluating the goals and other incentives of the program. The GAO report will be issued to Congress no later than January 31, 2020.

3015. Amendments to Orphan Drug Act to Include Grants

Section 3015 of the Act clarifies the use of orphan drug grants to include a broader development process of drugs that treat rare diseases.

The scope of these grants is clarified to include prospective observational studies and other analyses to better understand the natural history of the disease and to aid the development of new therapies. These studies may include investigations into the genotypic and phenotypic variability of disease manifestations, identification of distinct subpopulations affected and development or validation of drug development tools (DDTs) related to a rare disease.

Find out more about DDTs and the mechanisms by which drug therapies are expected to advance under the Cures Act in the next Regulatory Radar post.

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