- Preterm births account for around 10% of live births in the US each year.
- Makena is currently the only FDA-approved drug to help reduce preterm labor risk.
- Covis Pharma Group, the sole manufacturer of Makena, announced the withdrawal of the drug from the market.
- Questions have been raised about Makena’s efficacy following a recent study.
- Preventative treatments to reduce preterm labor risk are urgently required.
Last week the Covis Pharma Group announced they were pulling the only drug approved by the Food and Drug Administration (FDA) to help prevent preterm birth.
Covis is voluntarily ceasing production of Makena, which was approved by the FDA in 2011.
The FDA has yet to officially withdraw approval.
The company said in a statement: “While we stand by Makena’s favorable benefit-risk profile … we are seeking to voluntarily withdraw the product and work with the FDA to effectuate an orderly wind-down.”
The New York Times first reported the news, and the decision comes after criticism that the drug is ineffective.
In October, the
Following the meeting, the committee recommended the FDA withdraw its approval.
The decision was predominantly based on a
The research involved over 1,700 pregnant women who had previously experienced preterm labor. It was found that women who received Makena had the same neonatal outcomes as those given a placebo.
These results contradict 2003 research findings that were used as the basis for the drug’s approval in 2011. This study, which involved 463 women in the US, indicated Makena was effective at reducing preterm birth risk.
However, during the recent
“It did not, however, directly address the ultimate clinical benefit of interest: whether Makena improves neonatal health outcomes.”
Because the larger, more recent trial findings indicated Makena does not improve neonatal health outcomes, the committee stated: “Its benefit-risk profile is unfavorable, and it should be withdrawn from the market.”
Makena was introduced to reduce the risk of preterm birth among pregnant women who had previously experienced one or more preterm births.
The drug is administered via injection. Treatments begin when the pregnancy is between 16 weeks, 0 days and 20 weeks, 6 days, said Dr. Mary Jacobson, a board-certified OB/GYN and chief medical advisor at Hello Alpha.
Injections continue weekly “until week 37 of gestation or delivery, whichever occurs first,” she noted to Healthline.
Makena’s primary ingredient is a synthetic form of progesterone called hydroxyprogesterone caproate (Intramuscular 17-OHPC).
“Progesterone is a progestational hormone which supports pregnancy by decreasing the vascular tone of the muscle of the uterus,” explained Jacobson.
In lowering this element of the uterus, “the risk of miscarriage and preterm birth [is reduced],” she said.
However, Sarah McBane, PharmD, Health Sciences Clinical Professor and Founding Associate Dean for Pharmacy Education at UCI School of Pharmacy & Pharmaceutical Sciences, noted that natural progesterone and hydroxyprogesterone caproate are two separate substances that act differently in the body.
For instance, “[natural] progesterone is known to prevent cervical ripening (the pre-labor process where the cervix softens and begins to open),” she shared. “Hydroxyprogesterone caproate has not demonstrated that effect.”
In light of this, Jacobson stated, “the mechanism by which Makena reduces the risk of recurrent preterm birth is unknown.”
Makena came to market in 2011 after receiving the go-ahead from the FDA through its ‘accelerated approval’ process.
Most drugs are approved following full clinical trials which demonstrate their efficacy and risk profile, explained Stacia Woodcock, PharmD, Pharmacy Editor at GoodRx. However, these “can take years to complete,” she told Healthline.
As such, “the accelerated approval process was developed to quickly get medications that fill an unmet need to patients with serious conditions,” Woodcock revealed.
Approval is given “based on preliminary data that shows the medication might be beneficial and is unlikely to cause harm.”
Following accelerated approval, explained Sarah McBane, PharmD, Health Sciences Clinical Professor and Founding Associate Dean for Pharmacy Education at UCI School of Pharmacy & Pharmaceutical Sciences, the FDA requires drug manufacturers to conduct further research on the drug’s safety and efficacy.
“If these studies are not conducted or do not show benefit, the FDA can withdraw the approval,” McBane told Healthline — and this is what has occurred with Makena.
So does this mean that drugs with less clinical data are more likely to be disapproved?
“It’s a bit more common (although still rare), simply because the approval must be re-evaluated once the full clinical studies are complete,” said Woodcock.
McBane noted that “manufacturers rarely pull their own products from the market. Similarly, the FDA rarely rescinds drug approvals.”
However, when they do, “these decisions [are based] on concerns about the safety or efficacy of medications,” she stated.
With Makena the only FDA-approved drug for preterm labor prevention, its withdrawal from the market will leave many pregnant women with a history of preterm birth feeling vulnerable.
So what other options are available?
“Progesterone injections or vaginal progesterone, in the form of Crinone gel or Endometrin inserts, are sometimes used off-label for people who have previously had a preterm birth or have a short cervix,” revealed Woodcock.
A few key lifestyle changes can also assist in reducing preterm labor risk, said McBane: “avoid smoking, alcohol, and illicit drugs, and get regular prenatal care.”
Ultimately, though, the current options are slim. “We need to identify other effective interventions to prevent recurrent preterm birth,” Jacobson asserted.
The Centers for Disease Control and Prevention (CDC)
“Preterm delivery is defined as birth less than 37 weeks gestation and is the leading cause of neonatal and infant mortality in the United States,” Dr. Tondra Newman, Maternal Fetal Medicine Specialist, shared with Healthline.
Despite both being early forms of labor, preterm birth and miscarriage aren’t the same.
“The difference technically revolves around the gestational age at the time of occurrence,” said Dr. Kecia Gaither, board-certified in OB/GYN and Maternal Fetal Medicine, Director of Perinatal Services/Maternal Fetal Medicine at NYC Health + Hospitals/Lincoln in the Bronx.
“Miscarriage refers to pregnancy loss before 22 weeks gestation,” she told Healthline.
It’s unknown what causes preterm births to occur, although it’s thought that various factors are at play.
“It is likely multifactorial, with contributions from the hormonal environment and the activation of pro-inflammatory pathways,” Newman explained.
Furthermore, certain individuals are at greater risk of experiencing preterm labor.
Newman shared that these include:
- Non-Hispanic, Black, and Indigenous women
- Adolescent women (under 20) and women of advanced maternal age (over 40)
- Women with a history of a prior preterm delivery
- Pregnancies resulting from IVF treatments
- Low socioeconomic status
- History of cervical incompetence
- Multiple gestations
- Smoking during pregnancy
Effects of preterm birth
Preterm birth survival rates depend on how far along the pregnancy is when labor occurs: a baby born at 31 weeks has around a 95% chance of survival, whereas a baby born at 24 weeks has a chance of about 60%.
Gaither revealed that infants born early are also at greater risk of developmental issues.
She explained that concerns that can arise include following preterm birth include:
- Central nervous system immaturity
- Increased brain hemorrhage risk
- Increased risk of cerebral palsy and learning disabilities
- Vision problems
- Lung and breathing issues
- Intestinal inflammation
- Poor feeding/growth
- Abnormal blood flow within the heart
With the number of preterm births on the rise, the urgent need for treatment approaches is evident.
Unfortunately, “because the exact underlying causative pathways for preterm birth have not been determined,” noted Newman, “there are substantial barriers to creating targets for prevention.”