House legislators set to markup legislation related to rare diseases, pediatric oncology and HCT/Ps

• The House Energy and Commerce Committee’s Subcommittee on Health will meet on Thursday, May 16 to mark up 23 pieces of legislation. A “markup” process involves votes on individual pieces of legislation, as well as amendments to those bills.
• While most of the legislation being considered is not relevant to the FDA, four of the bills are. In brief, the Give Kids a Chance Act proposes to create new pediatric testing requirements for developers of oncology drugs. The Retaining Access and Restoring Exclusivity (RARE) Act proposes to modify orphan drug eligibility requirements to close a loophole that was the subject of recent litigation. The Creating Hope Reauthorization Act would reauthorize the FDA’s Rare Pediatric Disease Priority Review Voucher program. And the Shandra Eisenga Human Cell and Tissue Product Safety Act would introduce new safety testing requirements for human cell and tissue products.
• The markup hearing comes three months after the E&C Committee last held a hearing on 18 bills related to rare diseases, including all four of the above-mentioned bills.

H.R. 7384: The Creating Hope Reauthorization Act of 2024

• This bill is relatively brief and simple. At present, the Priority Review Voucher program for rare pediatric diseases is due to expire at the end of this fiscal year. At that time, the FDA would no longer be able to award new vouchers to companies, unless the product already had rare pediatric disease designation, and obtained approval before October 1, 2026.
• The Creating Hope Reauthorization Act would extend the expiration date of the program for another four years, from September 30, 2024 to September 30, 2028.

H.R. 3433, Give Kids a Chance Act

• This legislation has been under development for several years, and as of today has a whopping 230 co-sponsors in the House of Representatives. The bill is effectively a successor to the RACE for Children Act of 2017, which became law as part of the FDA Reauthorization Act of 2017 (FDARA). The law required some drug sponsors to assess the efficacy of adult cancer treatments in children under specific conditions. As the legislation explained, the FDA could require the sponsor of an approved “molecularly targeted” medicine to complete a pediatric assessment if the target is “germane” to a pediatric cancer, either in terms of the number of patients or the therapeutic benefit over existing therapies.
• The Give Kids a Chance Act extends the RACE for Children Act’s requirements one major step farther, applying them to combination therapies in addition to single-drug therapies. Combination products could include standards of care or other therapies owned by the same sponsor as the primary drug. The requirements would apply only if the new product contains a “single new active ingredient” or if the “combination of active ingredients has not previously been approved” in combination with one another.
• The text of the bill hasn’t changed since it was last introduced in May 2023, although the legislation has considerably more legislative co-sponsors than it did previously. Previous AgencyIQ analysis of the legislation noted concerns that may have contributed to it not passing as part of prior legislation. [ Read AgencyIQ’s extensive analysis of this legislation from May 2023 here.]

H.R. 7383, Retaining Access and Restoring Exclusivity (RARE) Act

• This proposed bill, sponsored by Reps. DORIS MATSUI (D-Calif.) and GUS BILIRAKIS (R-Fla.), focuses on marketing exclusivity periods granted to orphan drugs. Following FDA approval, these products are granted seven years of marketing exclusivity, preventing FDA from approving the “same drug for the same disease or condition” if the applicant does not have the right to reference the product (i.e., is not the original sponsor). However, there are a few notable exceptions: FDA can approve a drug for an already-approved orphan indication if the new drug is clinically superior, or if the original sponsor is unable to manufacture the product at the level required to meet current patient needs.
• The scope of the orphan drug exclusivity provision has been subject to recent debate, primarily due to the high-profile court case, Catalyst v. Becerra. As a result, a handful of bills on orphan drug exclusivity have been introduced in Congress in the last few years, including a companion bill of the same name as H.R. 7383 (the RARE Act) that was introduced back in April 2023 by Sen. TAMMY BALDWIN (D-Wisc.).
• The details on Catalyst: The FDA approved Catalyst Pharma’s Firdapse (amifampridine) for the treatment of adults with Lambert-Eaton myasthenic syndrome (LEMS), a very rare autoimmune condition, in 2018. However, the FDA then approved another amifampridine product, Ruzurgi, in 2019 for the treatment of LEMS in pediatric patients. Interestingly, the sponsor that developed Ruzurgi (Jacobus) had received an orphan drug designation from the FDA back in 1990. The FDA asserted that its long-standing interpretation of the Orphan Drug statute, codified in existing regulations, was that orphan drug exclusivity applies only to the specific “use or indication” for which the drug is approved, rather than for the entire “orphan-designated disease or condition.” However, Catalyst disagreed, stating that FDA’s approval of Firdapse for adults meant that the Agency shouldn’t have approved another drug for the same condition, even if the indication was for a different patient group. In late 2021 a federal Court of Appeals finally settled the case, siding with Catalyst that FDA had erred in approving Ruzurgi after Firdapse. [Read Agency IQ’s analysis of the court decision and FDA’s interpretation of it here]
• The RARE Act seeks to clarify the scope of the Orphan Drug Act to align with FDA’s stance in the Catalyst case. If passed, the RARE act would give seven years of marketing exclusivity to products awarded orphan drug designation by the FDA, but only for the specific indication they are approved to treat, and for which they received exclusivity. This means that FDA could approve other products that treat the “same rare disease or condition” as an orphan-designated drug product as long as the subsequent products are approved to treat different indications than the original product.

H.R. 7188, Shandra Eisenga Human Cell and Tissue Product Safety Act

• This legislation targets human cell and tissue products and the establishments at which they are produced or processed. It would introduce civil penalties for companies that violate statutory requirements under the FDA’s 21 C.F.R. 1271, up to $20,000 for each violation, $20,000 for each day of a continuing violation, and “an amount equal to the retail value of the human cell and tissue products that are the subject of the violation.” Maximum penalties could be assessed at $10 million, according to the legislation.
• FDA is also called on to eventually improve the safety of human cell and tissue products (HCT/Ps). The bill would require a report to Congress on the actions that FDA could take to improve safety, to include “recommendations on potential guidance or regulations that could be issued or promulgated, as applicable, to improve donor screening for human cell and tissue products.” Within one year of the bill’s enactment, the FDA would also need to “initiate a review of existing guidance for determining eligibility of donors” of HCT/Ps and issue updated guidance within three years.
• While the legislation is intended as a response to the death of a Michigan resident from a tuberculosis outbreak caused by a donated tissue product, the effects are likely to be far more widespread. While the bill is aimed at resolving bad tissue practices, FDA could potentially use this authority to go after stem cell companies that fail to register their products as new drugs. The definitions within the bill state that it applies to “articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient,” which the FDA has long considered to include stem cells. While the FDA doesn’t need new authority to go after stem cell practices, the new authority to levy significant fines against companies in this space could give the FDA a powerful tool with which to compel compliance.

Featuring prior research from Rachel Coe

To contact the author of this analysis, please email Alexander Gaffney ( agaffney@agencyiq.com)
To contact the editor of this analysis, please email Kari Oakes ( koakes@agencyiq.com)

Key Documents and Dates

• A Subcommittee on Health markup of 23 legislative proposals, Wednesday, May 16, 2024