Background

On April 7, a US District court ruling in Texas in The Alliance for Hippocratic Medicine v. U.S. Food and Drug Administration (FDA), issued a preliminary injunction, partially in favor of the plaintiffs, citing the public’s interest and resulting in a less restrictive ruling. The court issued a Section 705 stay “temporarily suspending” the FDA’s authority and the effective date of the FDA’s initial approval of mifepristone. The drug, commonly used in combination with misoprostol for medication abortions, received FDA approval in 2000. The Department of Justice has appealed the Texas decision and filed an emergency motion to block the decision from going into effect until after the appeal has been heard. On April 12, plaintiffs sought a nationwide injunction, but the federal appeals court issued a preliminary injunction, ruling partially in favor of the plaintiffs. The Justice Department has expressed intent to seek “emergency relief from the Supreme Court to defend the FDA’s scientific judgment.” In a separate case, Washington State et al. v. FDA, 12 Democratic states challenged the FDA’s restrictions on mifepristone’s distribution. The presiding judge issued an injunction preventing any changes to the drug’s current availability under its January 2023 Risk Evaluation and Mitigation Strategy (REMS).

Implications of Case Rulings

Stakeholders and the media have engaged in a robust conversation about the rulings’ effects on access to medication abortion and existing disparities based on factors such as geography. However, these decisions also raise broader questions about the implications to the regulatory process and access to similar products that may face political opposition. The questions below begin to explore these impacts that extend beyond abortion to other FDA decisions regarding historical court deference to agency interpretation of statutes and regulations, approvals of products that may face political opposition, and access and coverage variations across states.

1. How will the Texas and Washington decisions impact future access to additional products under public scrutiny?

As with abortion medications, vaccines and other products have been subject to public scrutiny. If the Texas court decision suspending agency approval is upheld, it may increase uncertainty around access to existing and pipeline products that could be controversial.

2. How will courts approach deference to federal agencies in subsequent cases?

The mifepristone rulings call into question the FDA’s consideration of safety and efficacy and interpretation of the statutory term “illness.” Historically, judicial deference is given to federal agencies to interpret statutory language and regulations following the 1984 landmark Supreme Court case, Chevron USA, Inc. v. Natural Resources Defense Council, Inc., and the 1997 case, Auer v. Robbins. However, deference to agency interpretation of statute and regulation has been increasingly challenged in court. In the Texas case, plaintiffs argued that Auer deference is inappropriate because Auer “requires courts to yield to an agency’s interpretation of an ambiguous regulation,” but in this case the regulation at hand is “plain and not ambiguous.” If the mifepristone decisions overturning or suspending FDA’s approvals are upheld, the rulings will add to recent Administrative Procedure Act cases challenging deference to FDA agency interpretation for subsequent court cases, thereby potentially increasing the risk of additional scrutiny of future FDA interpretations of statute or regulations.

3. What will manufacturers need to consider when pursuing new indications to limit uncertainty in access?

Manufacturers analyzing current or planned label language and clinical trial design have other issues to consider as well, because the Texas decision also weighed in on minor deviations between conditions of use and clinical trial protocols for mifepristone. This may result in uncertainty around future use of clinical trial criteria in label language, approval of indications to label, or appropriateness of current label language. Questions also remain about whether off-label use for similar drugs may be subject to a similarly high degree of scrutiny.

The plaintiff in The Alliance for Hippocratic Medicine v. FDA argued that the agency was “arbitrary and capricious” in the label requirements for mifepristone, saying that the label omits protocols originally used in US clinical trials submitted as evidence for approval. The FDA reviewed the label and the REMS in 2016 following an evidence-based request from the manufacturer. The review concluded that there was sufficient evidence to omit certain original protocols due to “no new safety concerns” and “the number of adverse events appear[ing] to be stable or decreasing.”

4. What will manufacturers need to consider when seeking product approvals through the accelerated approval pathway?

The Texas case scrutinizes Subpart H and the FDA’s accelerated approval pathway (AAP), creating another consideration for stakeholders planning to use or currently utilizing the AAP to develop a product. The accelerated approval pathway  has also been in the spotlight recently due to legislative and regulatory reforms. For example, legislation has been proposed in Congress to increase funding for oversight of the accelerated approval process and the creation of a cross-disciplinary oversight council. These cases are likely to further increase scrutiny of the pathway, adding to the factors manufacturers must take into account if they are considering utilizing the pathway or already proceeding in developing a product via the AAP.

5. How will REMS be operationalized under varying guidance from courts, agency, and states?

With conflicting opinions on the mifepristone REMS, the rulings also raise questions about the implementation of REMS requirements across varying guidance.  The Washington plaintiffs contend they “seek to enjoin the application of any REMS, such that mifepristone can be prescribed just like the 20,000+ other drugs that don’t have one”. Although the FDA’s decisions around the REMS is federal, states may impose additional restrictions outside of the REMS that restrict access to FDA-approved products, such as Mississippi’s requirements of a 24-hour waiting period for dispensing mifepristone following initial examination and ingestion of the drug in the presence of the prescriber. Conflicting guidance on restrictions of use can lead to variation in access and potentially worsened disparities in medical care.

6. How will the conflicting interpretations of statute for the term “illness” between courts and agency impact coverage of pipeline and on-market products?

Plaintiffs in the Texas case contend that pregnancy is not an illness and therefore the FDA was “exceeding its authority” by approving mifepristone under Subpart H. Plaintiffs define “illness” as “an unhealthy condition of body or mind” or “a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury.” A  2008 review conducted by the Government Accountability Office on the FDA’s approval and oversight of mifepristone found that the FDA concluded in its third and final review of the drug application that “termination of unwanted pregnancy is a serious condition and imposing restrictions under Subpart H was necessary.” If ultimately upheld, the Texas decision could increase risks associated with the durability of coverage and approval of prophylactics and other existing and pipeline products targeting conditions that do not meet the definition of “illness” as defined by the case.

Future Outlook

Amid all this uncertainty, stakeholders should monitor future court decisions and stakeholder actions to understand potential impacts on access to other FDA-approved products. To learn how Avalere’s regulatory experts can help provide a 360° perspective on potential risks and implications for product success, connect with us.