Opinion: FDA: Ignore a pharma company’s deceptive racial equity argument for keeping Makena, an ineffective preterm labor drug

In an effort to sway the Food and Drug Administration not to withdraw accelerated approval of Makena, a drug developed to prevent preterm birth that does no such thing, a pharmaceutical company owned by a private equity company is making the specious argument that the drug should be kept on the market because it may — the emphasis is mine — work in Black people.

Any legitimate effort to reduce preterm birth and other complications of pregnancy and childbirth in the Black community should be applauded and pursued. This isn’t one of them. It is, instead, an outrageous ploy to preserve corporate profits that has a high likelihood of harming Black mothers and babies.

Makena is the current brand name of 17 alpha-hydroxyprogesterone caproate. Originally developed as Delalutin in the 1950s by Bristol Myers Squibb, it is now being marketed and sold by Luxembourg-based Covis Pharma, which is owned by the private equity giant Apollo Global Management.


The evidence base for the use of Makena is less than flimsy.

In 2003, a small clinical trial funded by the U.S. National Institute of Child Health and Human Development seemed to show that 17 alpha-hydroxyprogesterone caproate could prevent preterm birth in women with a prior preterm birth. But this trial, called the Meis trial after the lead author, was fatally flawed: Participants in the placebo group were at higher risk of preterm birth than those in the Makena group (meaning something went wrong with the randomization), the study site with the largest number of participants had aberrant results, and the placebo group had a far higher preterm birth rate (55%) than expected.


Perhaps most importantly, the Meis trial did not show any benefit for the babies. Though the rate of preterm birth was lower in the Makena group, there was no improvement in babies’ health.

Despite these problems, non-FDA-approved versions of 17 alpha-hydroxyprogesterone caproate made by compounding pharmacies, costing about $15 a dose, quickly came into widespread use after 2003.

In 2006, Adeza Biomedical applied to the FDA for accelerated approval of a brand-name version of 17 alpha-hydroxyprogesterone caproate. Concerns were raised regarding the Meis trial by FDA officials, the Harvard-affiliated obstetrician/gynecologist who wrote the editorial that accompanied the report of the Meis trial in the New England Journal of Medicine, and many in the obstetrics and maternal-fetal medicine communities. In particular, the FDA’s chief statistical reviewer stated: “From a statistical perspective, the level of evidence from [the Meis trial] is not sufficient to support the effectiveness of [Makena]… Without a second study, the generalizability of the study results to a larger population cannot be assessed.”

Despite the concerns, the FDA granted accelerated approval to 17 alpha-hydroxyprogesterone caproate under the brand name Makena in 2011, with the stipulation that a confirmatory trial be performed. The results of that trial, Progestin’s Role in Optimizing Neonatal Gestation (PROLONG), published in 2019, showed that Makena failed to reduce preterm births and offered no benefits for babies.

When these results were announced, many expected that the use of Makena would stop. After all, why inject pregnant women with a synthetic hormone that costs $800 a dose, doesn’t prevent preterm birth, and provides no health benefit?

That’s when the deceptive spin campaign began. Makena champions (many of which are pharma-funded) began making the argument that the Meis trial, which showed a small reduction in preterm births, was conducted in the U.S. with nearly 60% of Black participants while PROLONG was an international trial with mostly white participants. They concluded that the drug may work for Black women and should be kept on the market to help the Black community and improve racial equity.

The FDA rejected this deceptive racial equity argument after analyzing both the Meis and PROLONG trials. It found no evidence of benefit in Black women. In October of 2020, the FDA formally proposed pulling Makena off the market. But AMAG Pharmaceuticals, which had acquired the rights to Makena and was itself subsequently acquired by Covis Pharma, objected to the proposal and asked for a hearing before the agency. That hearing begins on Oct. 17.

In the run-up to the hearing, pro-Makena sources have continued to hammer away on the racial equity argument. Because Black women are at higher risk for preterm birth than white women (which is true), they argue it is important to keep Makena on the market to help serve the at-risk Black community and fight for racial equity. Take, for example, the comment submitted in advance of the FDA hearing by Martha Nolan, a senior policy adviser for HealthyWomen, claiming that taking Makena off the market will “exacerbate an ever increasing maternal health disparity in maternal and infant health outcomes between Black, Indigenous, and women of color and their white counterparts.” HealthyWomen is funded by pharmaceutical companies, and Covis Pharma is on the organization’s corporate advisory council.

But Makena has not been shown to decrease preterm birth in people of any race. How does keeping Makena on the market — so pregnant Black women can disproportionally be injected with an ineffective drug — improve racial equity in any way?

If this false argument prevails, and the FDA allows Makena to stay on the market, Black women will be more likely to be treated with this ineffective and potentially dangerous drug.

The history of medicine is littered with examples of Black people being treated differently than white people, and with tragic results. Makena has risks of injection site reactions, blood clots, depression, gestational diabetes, stillbirth, unknown effects on the developing fetal brain, and possibly increased rates of cancer in the exposed offspring.

No one should be fooled by the racial equity spin for Makena. The notion that preferentially giving it to Black mothers will improve racial equity is absurd. Keeping it on the market does nothing to help racial equity — it just puts Black mothers and their babies at risk.

Adam C. Urato is a maternal-fetal medicine physician in Framingham, Mass. He has previously petitioned the FDA, with Public Citizen, to remove Makena from the market.

Source: STAT