As an Oct. 29 regulatory meeting nears to review the Makena treatment for preventing premature births, a consumer advocacy group is urging the Food and Drug Administration to immediately withdraw the controversial drug because it failed a confirmatory study.

In a citizen’s petition being filed with the FDA on Tuesday, Public Citizen pointed to a required followup effectiveness study that was released in March, showing Makena is no better than a placebo in preventing preterm birth or major complications from preterm birth. The advocacy group also argued the agency erred when it endorsed the medicine in 2011 under the accelerated approval program, because data from a Phase 3 study that largely formed the basis for approval was “seriously flawed.”

The advocacy group maintained that prior to approval, FDA reviewers raised “serious concerns and identified major deficiencies” in the initial application. As an example, Public Citizen noted that an FDA staffer noted that the pre-specified primary outcome for the late-stage trial — preterm delivery before 37 weeks of gestation — was not an appropriate endpoint to establish effectiveness.


“It is inconceivable that the FDA would have approved Makena if the efficacy data from the post-market trial showing no benefit had been available prior to approval and the only appropriate course of action now is obvious — the drug must be taken off the market,” Public Citizen wrote in its petition. The advocacy group also wants the FDA to prevent compounding pharmacies from supplying the drug.

A spokeswoman for AMAG Pharmaceuticals (AMAG), which sells Makena, wrote us to say that, “upon cursory review, this Citizen’s Petition drudges up old questions that were raised by the FDA in its initial 2006 review. These questions were adequately addressed and the FDA granted approval… in 2011. (Makena) remains the only FDA-approved treatment currently available for pregnant women who have had a prior spontaneous preterm birth, which is the leading risk factor for preterm birth.”

By scheduling an Oct. 29 advisory panel meeting to review the trial results, the FDA fueled speculation the drug may indeed be withdrawn, an outcome with which some Wall Street analysts agreed at the time the study results appeared last March.

This week, however, one analyst suggested the FDA panel may recommend keeping Makena on the market.

Why? After polling 50 obstetricians and gynecologists, SVB Leerink analyst Ami Fadia found that only 6% of those surveyed believed a lack of effectiveness was the most likely reason behind the failure found in the followup trial. Moreover, 92% would vote to keep Makena on the market, and, despite the study results, 86% anticipated no change to their current prescribing habits if Makena remains available.

“Multiple reasons seem to, in totality, side in favor of retaining approval,” based on the views expressed by the physicians, Fadia wrote in an investor note. The “failure (of the follow-up study was) more likely due to the patient population or the high bar for success, based on the (physician) responses, which we believe renders (the study) results inconclusive” on using Makena.

As we noted previously, the post-marketing study thrust Makena into the headlines nearly a decade after it became one of the earliest examples of price gouging by a drug maker, an episode that also saw the FDA become ensnared in controversy over the cost of a medicine.

We will repeat the back story: In 2011, a small company called K-V Pharmaceuticals won approval for Makena, which was a decades-old compound, and snagged orphan drug designation. This meant K-V had seven years of marketing exclusivity and could preclude compound pharmacies from making their own versions.

However, K-V, which relied on limited data from a study sponsored by the National Institutes of Health to gain an accelerated approval, was required to run a confirmatory study. Meanwhile, the company ran into big trouble for charging $1,500, compared with $10 to $20 a week for compounded versions.

The move infuriated physicians and consumer advocates, prompting the FDA to decide not to prevent compounders from compounding. The ruckus was one of the first signs of pushback over such pricing maneuvers, which later became increasingly common in the pharmaceutical industry.

Normally, the FDA would have banned the sale of older, unapproved drugs. But the Obama administration was concerned about the searing publicity over Makena pricing because a federal agency had allowed a monopoly to develop.

Later, K-V sued the FDA, and a judge ruled in favor of the agency although the case was later settled in 2014 and terms were not disclosed. By then, the company changed its name to Lumara Health, which AMAG acquired for $675 million. Since then, Makena has been a big seller, generating $322 million in revenue last year, but otherwise receded from view — until the study results were released in March.

“It makes no sense to inject women with a synthetic hormone that carries risks — including injection site reactions, possibly increased rates of gestational diabetes and the unknown long-term adverse effects to the baby — but offers no meaningful benefits,” said Dr. Adam Urato, chief of maternal-fetal medicine at MetroWest Medical Center in Framingham, Mass., who filed the Public Citizen petition. “The FDA must pull this product off the market.”

Leave a Comment

Please enter your name.
Please enter a comment.

  • It is useful to know about this, but please, STAT, indicate the real name of the drug in the story (hydroxyprogesterone) instead of using yet another cute made up trade name. We have known for a very long time that progestogens do not provide benefit in early pregnancy. Using new names allows companies to pretend they have a new drug, and invent new stories about it.

    • Hi James Dickinson,

      Thanks for the note and you make a fair point. Although I generally refer to medicines by their trade names, there are times when the chemical name can be useful to know – and you offer a good explanation in this case.

      So going forward, I will keep that in mind.

      ed at pharmalot

A roundup of STAT’s top stories of the day in science and medicine

Privacy Policy