Appeals court reinforces concerns over abortion ruling

Biotech industry, former FDA leaders say ruling could erode integrity of drug regulation

A federal appeals court ruling that allows continued access, on a restricted basis, to abortion drug mifepristone does not extinguish concerns expressed by the biopharma industry, former FDA leaders and the Biden administration that a lower court ruling will destabilize FDA regulation of drugs.

In an order released Wednesday night, the Fifth Circuit Court of Appeals put parts of a ruling by Judge Matthew Kacsmaryk of the U.S. District Court for the Northern District of Texas on hold and allowed other parts to remain in force.

The three-judge panel drawn from the Fifth Circuit decided that Kacsmaryk’s decision to completely overturn FDA’s original approval of mifepristone 23 years ago was incorrect because the plaintiffs in the case took too long to make the request. The panel upheld his decision to stay FDA’s more recent decisions to relax restrictions on the use and distribution of the drug.

The Fifth Circuit’s reinstated requirements for women to visit physicians three times in the course of treatment and suspended an FDA decision to allow distribution of mifepristone through the mail.

The Fifth Circuit ruled only on the Department of Justice’s request to put Kacsmaryk’s ruling on hold while the case is litigated.

The three-judge panel ordered that the appeal be expedited to the next available opening for oral arguments. Those arguments will be heard by a randomly selected panel of Fifth Circuit judges.

Apart from the impact on access to mifepristone, former FDA attorneys and biopharma industry leaders told BioCentury they are disappointed in the ruling because it reiterated aspects of Kacsmaryk’s ruling they believe are at odds with laws governing drug regulation and fails to give proper deference to the agency’s scientific and medical expertise.

Attorney General Merrick Garland alluded to these concerns in a statement announcing the administration’s intention to appeal the Fifth Circuit’s ruling to the Supreme Court. “We will be seeking emergency relief from the Supreme Court to defend the FDA’s scientific judgment and protect Americans’ access to safe and effective reproductive care.”

On Friday, Supreme Court Justice Samuel Alito put a five-day hold on implementation of a Texas district court’s decision to overturn FDA’s approval of the abortion drug mifepristone.

Joshua Sharfstein, who served as FDA principal deputy commissioner during the Obama administration told BioCentury that “if it is allowed to stand, the opinion will still be very disruptive to clinical care for many. For obviously ideological reasons, the judges are claiming that they understand the science of medication safety far better than the experts of the FDA.” Sharfstein is vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Health.

Sharfstein co-authored a commentary with former FDA Commissioner Margaret Hamburg that defended the agency’s approval and regulation of mifepristone and warned of larger consequences if the Texas district court ruling is not overturned. “Once courts dismiss core scientific judgments by the agency, there is no reason to believe they will limit themselves to this one medication.”

Hamburg and Sharfstein warned: “If judges begin to dictate the terms of medication access, then others will seek to use ideology and influence to advance their agendas.”

Appeals court ‘embraces’ district court ruling

The appeals court largely ignored briefs from the biopharma industry and Democratic members of Congress who argued that the district court had completely misinterpreted well settled FDA law.

“The Fifth Circuit’s ruling embraces some of the worst aspects of the district court’s reasoning, including the notion that all labeling changes must be supported by specific types of clinical studies that evaluate the specific precise proposed changes,” Eva Temkin, a partner at King & Spalding who wrote an amicus brief urging the Fifth Circuit to overturn Kacsmaryk’s decision, told BioCentury.

Temkin is a former associate chief counsel at FDA. The King & Spalding brief has been widely endorsed by the biotech industry, including by BIO, Pfizer Inc. (NYSE:PFE), Gilead Sciences Inc. (NASDAQ:GILD), Nkarta Inc. (NASDAQ:NKTX) and RA Capital Management, as well as over 100 biotech CEOs and investors.

The Fifth Circuit judges said FDA should not have relaxed REMS restrictions, or safeguards, on the use of mifepristone based on “studies that included those very safeguards.” In effect, they said the agency cannot change a REMS protocol unless it has data from a study that has conditions identical to those in the new protocol.

Rather than repudiate the arguments Kacsmaryk used to justify overturning FDA’s approval of mifepristone, the Fifth Circuit decision “continues to second-guess FDA’s scientific decision-making and to misapply applicable legal requirements,” Temkin said. “It continues on the same dangerous trajectory that can have a chilling effect on innovation and drug development.”

“The decision continues to inappropriately restrict FDA’s regulatory authority,” Rachel King, BIO’s interim CEO, told BioCentury. “The concerns we had with the initial ruling by the district court remain. As the case advances, BIO will continue to advocate for the preeminence of FDA’s regulatory authority.”

Elizabeth Jeffords, president and CEO Iolyx Therapeutics and a member of BIO’s Board of Directors, told BioCentury she was “surprised and disappointed by the Fifth Circuit’s midnight ruling, which seemed to ignore the multiple and deep flaws in the original ruling.”

Jeffords, who worked with King & Spalding on drafting the industry amicus brief, said that by ruling against Kacsmaryk principally on the statute of limitations issue, the appeals court failed to address aspects of his ruling that concern life sciences companies. “Rather than addressing the lack of scientific rigor provided, the glaring implications of judicial overreach, or the long-term risks to patient safety of weakening the FDA’s regulatory oversight, the Fifth Circuit seemed to focus on one procedural item.”

Attorneys involved in the litigation told BioCentury they had expected the Fifth Circuit to overturn the case by ruling that the plaintiffs lacked legal standing to bring the suit because they have not been and cannot expect to be harmed by FDA’s approval of mifepristone.

Leaving aside the merits of allowing physicians to have standing because they may have to treat a patient suffering from a drug’s adverse event, the Fifth Circuit seems to have misinterpreted the mifepristone patient agreement form. The ruling asserts that in cases when mifepristone is ineffective, FDA instructs women to seek emergency care. In fact, the form states that in such circumstances women should consult a physician “about a surgical procedure to end their pregnancies.”

The appeals court ruled that the emergency room physicians who are parties to the lawsuit “have a concrete, particularized injury since they have provided—and with certainty will continue to provide—the ‘emergency care’” that is required as a result of rare serious instances when mifepristone is not effective.

The court also said the “enormous stress and pressure” on physicians who treat women who experience adverse events associated with mifepristone confers legal standing on the plaintiffs.

If it is upheld, this logic “would allow a single medical provider anywhere in the country to claim standing to challenge any government policy that (even arguably) increases the health risk to any person,” Steve Vladeck, a law professor at the University of Texas School of Law, wrote in an analysis of the case posted Thursday.