FDA Withdraws Approval of a Premature Birth Drug After 12 Years

On April 6, 2023, the FDA Commissioner Robert M. Califf, MD, and Chief Scientist Namandjé Bumpus, PhD, announced the organization’s decision to withdraw the approval of Makena — also known as hydroxyprogesterone caproate or HCP — and its generics. The preterm birth drug was approved 12 years ago, in 2011, to delay preterm birth. However, proven inefficacy and side effects of the medication warranted withdrawn approval.

Initially, the drug was granted accelerated approval by the FDA to minimize the risk of preterm birth for individuals with a history of singleton spontaneous preterm births. Early clinical trials indicated that the drug could reduce the number of deliveries before 37 gestational weeks.

At the time, the FDA strongly considered reducing preterm births a critical endpoint, justifying the drug’s speedy approval.

According to the CDC, roughly 10% of infants born in the United States are preterm, with the highest rates of preterm birth being in Black individuals. Data suggests that Black individuals are 5.3% more likely to have a preterm birth than White individuals, at 14.8% and 9.5%, respectively.

Data from 2020 determined that 16% of infant deaths are associated with preterm birth. Additionally, preterm infants may go on to develop breathing problems — a likely cause of sudden infant death syndrome, feeding difficulties, cerebral palsy, developmental delays, visual issues, and auditory problems.

While preventing the fatal and life-changing outcomes of preterm birth is valuable, confirmatory studies on Makena found that the drug was ineffective. Considering its lack of efficacy and the associated side effects, including blood clots, injection site pain, itching, bruising, swelling, nausea, and diarrhea, the FDA decided to take the drugs off the market.

This action emphasizes the importance of confirmatory trials and FDA oversight of drugs and treatments granted accelerated approval.

“It is tragic that the scientific research and medical communities have not yet found a treatment shown to be effective in preventing preterm birth and improving neonatal outcomes — particularly in light of the fact that this serious condition has a disparate impact on communities of color, especially Black women,” said Califf, in the FDA press release. “Fundamentally, however, the touchstone of FDA drug approval is a favorable benefit–risk assessment; without that favorable assessment, the drug should not have the status of being FDA-approved.”