- Makena, a marketed therapy meant to reduce the risk of preterm birth for certain women, didn't meet the co-primary endpoints of a confirmatory study, according to its manufacturer AMAG Pharmaceuticals.
- Results from the PROLONG study showed Makena failed to significantly reduce the rate of preterm delivery at less than 35 weeks compared to placebo. There was also no major difference between the two treatment groups when it came to the rate of neonatal mortality or morbidity.
- Julie Krop, AMAG's chief medical officer, claimed patients in PROLONG had "very different demographics" versus an earlier trial that served as the cornerstone for Makena's approval with the Food and Drug Administration. Due to those inconsistencies, AMAG will do additional sub-group analyses of the PROLONG data — although Wall Street analysts are skeptical of the drug's commercial future.
Outgoing FDA Commissioner Scott Gottlieb will be remembered, both by supporters and critics, for the role he played in speeding more medicines to market. Data from the agency cited by Evaluate details how accelerated approvals based on surrogate endpoints rose dramatically while Gottlieb was in office, with 37 happening over the course of 2017 and 2018.
Yet the number of accelerated approvals was steadily growing long before Gottlieb took office. There were three in 2009, four in 2010 and six in 2011 — one of which was for Makena (hydroxyprogesterone caproate).
Regulators cleared Makena as a treatment for reducing preterm births for women pregnant with a single child who have a history of singleton spontaneous preterm birth. The decision was based on a what Cowen & Co.'s Ken Cacciatore calls a "limited and controversial" study, which found the percentage of women having births before 37 weeks of gestation was significantly lower (at 37.1% versus 54.9%) for those receiving Makena rather than placebo.
Makena faced challenges after getting approved, particularly when it came to pricing.
Drug compounders had for years been creating a very cheap version of Makena's active ingredient. The process continued even as the new brand came to market, crimping sales and putting its then-manufacturer K-V Pharmaceutical in a tight financial position. Not long after Makena's market entry, the company sued the FDA for not properly addressing the compounding issue. It would later file for bankruptcy, change its name, and get acquired piecemeal by Perrigo and AMAG.
Despite the controversies, Makena has remained on the market. Its latest clinical failure may not change much either, according to Cacciatore.
In a March 8 investor note, the Cowen analyst argued that pulling Makena from market won't decrease the demand for such products. As such, patients would have to get them through compounding facilities — something the FDA would likely try to avoid.
"Although there is still a significant portion of the of the market (roughly 30%) that sources through compounded pharmacies, we believe that it is unlikely that the Agency would want the market to go completely unregulated and not have the option for clinicians/patients to source through FDA validated facilities," Cacciatore wrote.
"For these reasons, we believe that the Agency will give significant leeway to the company to analyze this study," he added. Cowen holds a "Market Perform" rating on AMAG.
Piper Jaffray also foresees the FDA leaving Makena on the market, though the drug is "likely dead" from a commercial perspective. The investment bank also isn't sold on AMAG's defense that the PROLONG data were negatively affected by which patients were enrolled. Company leadership said most of the study's patients were from outside of the U.S., predominantly from Eastern European countries.
"Management indicates PROLONG patients were generally much lower risk than U.S. patients," Piper's Christopher Raymond wrote in a March 8 note. "We see things a little differently: this was a confirmatory trial designed to gain full approval and it failed. Downplaying these data as irrelevant is a huge stretch, in our view."
AMAG stock was down more than 20% in late-morning trading Friday.