FDA, in a RARE Act, Takes To Lobbying for a Change to the Orphan Drug Act

We’re in the midst of UFA (User Fee Act) season!  It’s the quinquennial event when many of the UFAs are up for reauthorization.  And with “must-pass” FDA legislation, comes a host of riders—pieces of FDA-related legislation not specific to UFA reauthorization, but that folks seek to get added to the UFA bill to address various issues and topics.  Often, it is industry that lobbies Congress to get the law amended to address some issue where FDA is being difficult or non-responsive; but don’t be fooled, FDA is also walking the halls of Congress looking for advocates for its own causes.  Usually FDA’s lobbying activities are done rather quietly.  Every once in a while, however, FDA is a bit bolder in its actions.  And that brings us to a May 12, 2022 FDA statement, titled “FDA’s Overview of Catalyst Pharms., Inc. v. Becerra.”  But before we go too far, some background is in order . . .

As we previously posted (here, here, and here), in Catalyst v. Becerra, Catalyst Pharmaceuticals, Inc. (“Catalyst”) sued FDA for approving the “same drug for the same disease or condition” as its orphan drug-designated product, FIRDAPSE (amifampridine) Tablets (NDA 208078), during its seven-year orphan drug exclusivity period.  FDA approved FIRDAPSE in November 2018, with a period of orphan drug exclusivity, for the treatment of Lambert-Eaton Myasthenic Syndrome (“LEMS”) in adult patients.  But in May 2019, FDA approved a second amifampridine drug product, Jacobus Pharmaceutical Company, Inc.’s (“Jacobus”) now-tentatively approved RUZURGI (amifampridine) Tablets (NDA 209321), for the treatment of pediatric patients with LEMS—a population generally acknowledged to be fewer than 30 in the U.S. and more likely 15-20.  FDA granted the approval despite Jacobus’ failure to conduct any of the routine studies expected for a pediatric approval, and all of RUZURGI’s efficacy data being for adult LEMS patients, the population within FIRDAPSE’s indication, rather than the FDA-approved indication.  FDA even described the process it followed to approve RUZURGI as “unprecedented” in in the Agency’s Catalyst court filings.  In any case, Catalyst sued FDA in June 2019 alleging that the plain language of the Orphan Drug Act precluded the Agency’s approval of RUZURGI in any LEMS patients until the expiration of the orphan drug exclusivity period covering FIRDAPSE.  Jacobus intervened, and the case made its way to the U.S. Court of Appeals for the Eleventh Circuit.

In September 2021, the Eleventh Circuit held that FDA’s interpretation of the Orphan Drug Act such that exclusivity was limited to the indication for which the drug was approved—rather than the disease or condition for which the drug was designated—is foreclosed by the plain language of the statute.  Consequently, the Court held that FDA’s approval of RUZURGI contravened the plain language of the Orphan Drug Act in violation of the Administrative Procedures Act and ordered FDA to rescind RUZURGI approval. . . which FDA ultimately did, converting the NDA approval to a tentative approval.  On April 7, 2022, Jacobus appealed the Eleventh Circuit’s decision to the U.S. Supreme Court in a Petition for Writ of Certiorari.

We’re all still waiting to hear whether or not the Supreme Court will take up the case.  But in the meantime, FDA has apparently been busy trying to get a legislative “fix” passed that would undo the Eleventh Circuit’s decision.  And UFA reauthorization provides the perfect vehicle for the Agency to try and get this accomplished.  A provision has already been included in H.R. 7667, the “Food and Drug Amendments of 2022,” which will be considered by the House Energy and Commerce Committee at a markup session on May 18, 2022, and that the Subcommittee on Health marked up and passed at a May 11, 2022 session (here and here).   Specifically, Section 811 of the bill, titled “Clarifying application of exclusive approval, certification, or licensure for drugs designated for rare diseases or conditions,” would amend the statute to replace the phrase “same disease or condition” (and similar phrases) with “same approved indication or use within such rare disease or condition” (and similar phrases).

But even before the House Energy and Commerce Committee acts, the Senate Health, Education, Labor and Pensions Committee held a April 26, 2022 hearing on UFA reauthorization.  During that hearing, FDA’s Patrizia Cavazzoni, M.D. and Peter Marks, M.D., Ph.D., in response to questions posed by Senators Tammy Baldwin (D-WI) and Bill Cassidy, M.D. (R-LA), spoke out about the Agency’s need for a legislative fix.   Dr. Cavazzoni commented that the Eleventh Circuit’s decision “will send a chill through the development of rare diseases and it will disproportionately affect children with rare diseases.”  Similarly, Dr. Marks commented that FDA sees the Eleventh Circuit decision “as a potential problem for the development of drugs for rare diseases,” and for pediatric indications in particular.

On May 11, 2022, Senators Baldwin and Cassidy introduced S. 4185, the “Retaining Access and Restoring Exclusivity Act” (“RARE Act”).  In a press release and in a backgrounder accompanying the introduction of the bill, which differs somewhat in language (but not intent) compared to the House bill, the Senators laid out their concerns with the Eleventh Circuit’s decision:

The court’s decision in Catalyst has far-reaching, adverse impacts, especially for children with rare diseases.  Without a fix, drug companies are incentivized to seek the broadest orphan drug designation as possible and then focus clinical studies only on the narrowest patient populations that would support approval.  In so doing, companies could then rely on the broader designated orphan disease and block approval for any different uses or other patient populations.

On May 12, 2022, just one day after the introduction of the RARE Act in the U.S. Senate, FDA took the highly unusual setp of issuing a statement—and essentially a press piece—titled “FDA’s Overview of Catalyst Pharms., Inc. v. Becerra.”  In it, FDA provides a brief overview of the Eleventh Circuit’s decision . .  and then lays out what the Agency terms “Key Impacts”:

• The Catalyst decision adversely resolves a statutory issue about the scope of ODE. The Catalyst decision interpreted the Orphan Drug Act to unambiguously tie ODE to the disease or condition for which the drug was designated, which would leave the FDA with no discretion to address the issue differently. In the coming months, the FDA will need to consider how the decision affects drugs with active terms of orphan drug exclusivity as well as currently marketed drugs, including generics. Going forward, the FDA expects that some drugs that are in late-stage development, or that have already been submitted for marketing application review, would be blocked from approval under the Catalyst decision’s interpretation of the Act.

• The Catalyst decision implicates approval of drugs for rare diseases. Because the FDA generally grants orphan-drug designation for the entire rare disease or condition—to incentivize sponsors early in drug development to study all persons with the rare disease or condition—and because FDA can only approve a drug for the specific indications for which there is adequate data in the marketing application, the designated disease or condition can represent a much broader population than the approved indication.

Sponsors could seek approval and exclusivity for their drugs by focusing on the smallest, easiest-to-study populations. Under the interpretation in the Catalyst decision, such an approval would result in exclusivity for their drug for the entire disease, even though the sponsors did not invest in studying and developing their drug for all individuals with the disease.

• The FDA expects that the Catalyst decision’s interpretation could adversely affect children—particularly the youngest pediatric populations—and other populations that are typically studied later in drug development. Because clinical studies in certain populations including children can be more challenging to conduct, sponsors often focus first on the populations who are easiest to study: adults with the fewest co-morbidities and complications. Except for certain oncology products, FDA cannot require pediatric studies of orphan-designated products. These barriers to development could mean that children (and other later-studied populations such as elderly individuals) would not have formulations, or dosing and safety information, appropriate for their needs for years after the product’s original approval.

While the FDA piece does not mention the RARE Act by name, the May 12, 2022 publication on FDA’s website—just one day after the introduction of the RARE Act—is more than coincidence.  It appears to be part of a concerted effort by FDA to lobby—and very publicly—for a change in the law.  That’s pretty unusual.  Just as curious is FDA’s messaging on the alleged effects on pediatric drug development.  Children are a perennial soft spot on Capitol Hill, and thus provide a good “in” for lobbying efforts.  But it’s unclear from FDA exactly how the Eleventh Circuit’s decision will affect pediatric drug development, particularly with the continued availability of other programs specifically designed to incentivize the research to support pediatric approvals and whether or not the the “race to approval” that occurred in the amifampridine situation will ever repeat itself in the next 40 years of the Orphan Drug Act.

To be clear, we’re not taking any particular position for or against the RARE Act in this post.  But FDA’s intense lobbying effort to legislatively reverse the Catalyst decision, and the arguments that the Agency is using to support that effort, deserve some mention and attention.