The biopharmas that objected to a Texas judge’s ruling suspending the approval of the abortion drug mifepristone are not content with just a letter. The companies have now banded together to support the U.S. government’s appeal in an amicus brief.
In the 4,542-word brief, the group of companies asked the U.S. Court of Appeals for the Fifth Circuit to grant the government’s request to stay a lower court’s ruling that blocked the decades-long approval of abortion drug mifepristone. U.S. District Judge Matthew Kacsmaryk’s April 7 ruling put access to the medicine in jeopardy across the country. However, another judge in Washington state then issued a conflicting ruling that preserved the approval of mifepristone in a dozen states and the District of Columbia.
“The district court’s decision will shatter FDA’s ‘gold standard’ of review,” the brief explains. The ruling “radically alters” the new drug application process, which companies use to get FDA approval for new medicines.
The Biotechnology Innovation Organization signed the brief, as did executives from Pfizer, InCarda, Day One Bio, Travere Therapeutics, RA Capital Management, Blueprint Medicines, Camp4 Therapeutics, Third Rock Ventures, Deerfield Management, Affini-T Therapeutics and hundreds more. The signatories “collectively hold hundreds of NDAs and anticipate filing many more for drugs currently in development.” They testified to the “substantial chilling effect” that the mifepristone ruling will have on drug development.
The brief criticizes the judge’s use of personal conclusions drawn from “cherry-picked” publications and anecdotes to replace the FDA’s “rigorous, data-driven scientific analysis.”
It also objects to the judge’s suggestions that head-to-head trials need to be conducted to demonstrate meaningful therapeutic benefit. There is no legal requirement to demonstrate a meaningful therapeutic benefit by any specific type of comparison and the FDA uses its discretion to determine this standard. For instance, if no approved drug exists for a condition, the FDA needs to be flexible in the evidence used to support a therapy meeting the standard. The judge’s decision could undermine that discretion and jeopardize other FDA approval processes such as breakthrough therapy designations or accelerated approvals, which use different standards for determining meaningful therapeutic benefit.
Another objection is that the judge ignored legal precedent and the Food, Drug, and Cosmetic Act and determined that the FDA failed to match the conditions of use for mifepristone’s label with those seen in the clinical trials that supported the drug’s approval. The FDCA does not require a perfect match between the conditions, but the judge determined that the FDA acted arbitrarily and capriciously in approving the drug anyway.
This sets a precedent that an approved drug’s label needs to match the conditions of a trial, which “has no basis in law,” according to the brief.
“Clinical trials are not intended to perfectly mirror real-world use conditions,” the brief argues. Clinical trials have restrictive eligibility criteria and monitoring procedures that go beyond what happens in real-world clinical practice.
If the ruling stands, the FDA would have to justify every single difference on the label that strays from the clinical trial. If the agency does not, the difference could be challenged by any party, creating a framework that is “rigid and unworkable,” according to the brief.
“Unless stayed, the district court’s lawless opinion will empower any plaintiff to grind drug approvals to a halt, disrupting patient’s access to critical medicines,” the brief added. “The outcome would chill crucial research and development, undermine the viability of investments in this important sector, and wreak havoc on drug development and approval generally, causing widespread harm to patients, providers, and the entire pharmaceutical industry.”
The case is Alliance for Hippocratic Medicine v. U.S. FDA in the U.S. Court of Appeals for the Fifth Circuit, #23-10362.