Congress Moves to Protect FDA Orphan Drug Act Upset in LEMS Ruling

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Leaders of the U.S. House Energy and Commerce Committee and two senators have taken action to clarify the original intent of the orphan drug act (ODA) that the U.S. Food and Drug Administration (FDA) applies to help speed therapy development for rare diseases.

Sens. Bill Cassidy, R-Louisiana, and Tammy Baldwin, D-Wisconsin, introduced bipartisan legislation called the Retaining Access and Restoring Exclusivity (RARE) Act. It aims to ensure proper incentives remain in place to foster robust rare disease therapy development and preserve access to treatments for patients. Similar language is in a House bill.

RARE comes as a response to a federal court ruling last year that made the FDA overturn its approval of Jacobus Pharmaceutical’s Ruzurgi (amifampridine) in treating children, ages 6–16, with Lambert-Eaton myasthenic syndrome (LEMS) — the only therapeutic option for this younger patient population.

In question was the scope of the seven-year market exclusivity period given to therapies designated an orphan drug by the FDA for a particular rare disease while in development, and later approved for that disease.

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Catalyst Pharmaceuticals sued the FDA in 2019 on the grounds that Ruzurgi’s approval violated the company’s right to market exclusivity for Firdapse (amifampridine), its own medication containing the same active ingredient as Ruzurgi. Firdapse was approved in 2018 under orphan drug status for LEMS patients, ages 17 and older.

While Ruzurgi’s FDA approval was initially upheld by a district court, that ruling was overturned by the U.S. Court of Appeals for the 11th Circuit, based in Atlanta.

Orphan drug designation — with its associated financial incentives, regulatory support, and seven years of U.S. market exclusivity — is granted under the ODA to therapies with the potential to fill an unmet medical need in rare diseases.

It was enacted in 1983 to attract industry interest in rare diseases, whose small patient communities often not only increase the cost of research and trials needed to show evidence of safety and efficacy, but also may limit such investments’ return.

Since the ODA’s start, the FDA considered orphan drug market exclusivity to apply only to a therapy’s specific approved use or indication within a rare disease or condition, rather than for the disease or condition itself.

Given that therapies often receive orphan drug designation for a particular rare disease, but are later approved for only a subset of patients, either based on age, disease subtype, or underlying mutations, the FDA’s interpretation helps serve different patient populations.

The RARE Act intends to solidify the FDA’s long-standing interpretation of ODA, giving the agency the necessary authority to approve treatments based on the same active ingredient from different manufacturers if they aim to treat distinct patient groups within a rare disease.

“Vague laws can be exploited, resulting in fewer patients getting the treatments they need to survive,” Sen. Cassidy, MD, said in a press release. “This bill clarifies the law to ensure incentives to innovate continue to produce lifesaving cures for our rarest diseases.”

The decision in Catalyst “has far-reaching, adverse impacts, especially for children with rare diseases and our bipartisan legislation aims to fix it so that patients aren’t locked out of approved treatments they should have access to,” said Sen. Baldwin.

“We are very encouraged by the legislation in both the House and Senate to clarify that orphan drug exclusivity is awarded only for the specific use that is approved by the FDA,” Peter L. Saltonstall, president and CEO of the National Organization for Rare Disorders (NORD), said in a separate press release.

“Since more than 90% of the 7,000 known rare diseases still have no treatment or cure, it is critical the robust incentives, as envisioned by the ODA, continue to exist so that new orphan drugs are developed into the future,” Saltonstall added.

In the absence of a legislative fix, NORD believes there would be fewer therapies approved for specific indications within rare disease populations.

“If the 11th Circuit decision is left in place, the law would create an incentive for sponsors to seek broader designations for an entire rare disease at the outset, leaving little incentive to continue to study the safety and efficacy [of a therapy] in special populations, like children,” NORD stated in its release.

The RARE Act (S. 4185), introduced on May 11, is currently before the Senate Committee on Health, Education, Labor and Pensions. Similar language introduced into the House committee’s Food and Drug Amendments of 2022 Act (H.R. 7667) was approved by its members on May 18.

Should these bills be enacted into law, whether Jacobus would be eligible to seek Ruzurgi’s re-approval in the U.S. for children with LEMS is still unclear.

Catalyst currently has in place a program called Catalyst Pathways that is meant to help adults with LEMS transition from Ruzurgi to Firdapse. While the program is not designed for children, the company has said its staff are available to help parents of children with LEMS identify means to gain access to Firdapse, such as through an expanded access program.

The company also expressed interest in requesting that the FDA expand Firdapse’s approval to include its use by children with LEMS.