New molecular entity
Development and Regulatory status
Jan 20The FDA expert panel recommended in October, in a 9-7 vote, that the FDA withdraw its approval of Makena. The seven dissenting members recommended keeping the drug on the market while conducting further study. So far, pending a final FDA decision, Makena is still on the market. The FDA does not have to accept the recommendations of its expert panels, though usually it does. The FDA has no established timeline for when it will announce whether it will withdraw its approval of Makena. Many doctors have suggested they will turn to compounded 17-hydroxyprogesterone caproate again if the licence for Makena is withdrawn .
Nov 19No longer listed on AMAG pipeline. Company has no UK presence so it appears no EU development is planned .
Oct 19The US FDA advisory panel recommends removal of hydroxyprogesterone caproate injection (Makena) from market following failed confirmatory trial; the PROLONG study did not meet 2 pre-specified co-primary endpoints (reduction of preterm birth, and a reduction in neonatal morbidity and mortality index) .
Mar 19Following dissapointing results from the PROLONG trial, the company announced plans to conduct additional sub-group analyses of the PROLONG data, particularly focusing on pts at highest risk of preterm delivery and the subset of pts enrolled in the US. 
Nov 15AMAG reported that it is developing a device for subcutaneous administration of Makena by an auto-injector and AMAG also reported that it is in the early stages of developing a longer-acting formulation of Makena, including conducting formulation work and pre-clinical studies to optimize the drug release profile .
May 15AMAG Pharmaceuticals receives a complete response letter from the FDA regarding its manufacturing supplement seeking approval for a single-dose vial of Makena. The FDA want more information about manufacturing procedures for the single-dose vial at a new third-party manufacturer. AMAG plans to respond .
Apr 14Plans for EU availability are uncertain
Apr 11Orphan status in US .
Mar 11Launched in the US .
Feb 11Approved in the US to reduce the risk of preterm delivery before 37 weeks of gestation, in pregnant women with a history of at least one spontaneous preterm birth .
Feb 11US approval was based on a study involving 463 women in which Makena reduced the proportion of women who delivered at 37 weeks of gestation (37% vs. 55% with placebo; n=463); no studies have demonstrated a direct clinical benefit (e.g. improvement in neonatal mortality/morbidity). As Makena® was approved under the FDA’s accelerated approval regulations, the manufacturer is required to conduct additional studies to demonstrate that the drug does have a clinical benefit .
A long-acting formulation of the small molecule hydroxyprogesterone
15 March 2013Around 50,000 babies are born prematurely in the UK each year. The UK has one of the highest rates of premature births in Europe. Very premature births occur at less than 32 weeks of gestation. They account for 1.4% of UK births but cause around 51% of infant deaths .
Trial or other data
Mar 19Topline results from the PIII PROLONG trial, which enrolled ~1700 pregnant women, did not demonstrate a statistically significant difference between Makena and placebo. For the co-primary endpoints: the incidence of preterm delivery at less than 35 weeks was 11% in the Makena treated group vs. 11.5% in the placebo gp (p=0.72). For the pts who met criteria for the pre-specified neonatal morbidity and mortality composite index, there was also no difference (Makena treated group 5.4% vs 5.2%, p=0.84). The adverse event profile between the two arms was comparable including miscarriage and stillbirth which were infrequent and similar between groups.
Dec 18Estimated study completion date of NCT01004029 (PROLONG) study is now Dec 18 .
Jan 17NCT01004029 (PROLONG) study recruitment ongoing. Estimated primary completion date now Jul 18 .
Jun 15NCT01004029 recruitment ongoing. The study is expected to complete in Dec 16 and final data collection for primary outcome measures is anticipated in Jun 16 .
Jan 14KV announced today it has enrolled 677 women in its ongoing international PIIIB safety and efficacy trial. 
Mar 13PIII (NCT01004029) trial is continuing recruitment .
Feb 11A PIII trial (NCT01004029) will recruit 1,707 women in the US, Canada, Czech Republic, Hungary, Spain, Ukraine & Russia. The primary outcome is rate of preterm birth <35 weeks of gestation in women with a singleton pregnancy, aged 18 years or older, with a previous singleton spontaneous preterm delivery. Secondary outcome is rate of neonatal mortality or morbidity, if and only if, the rate of preterm birth <35 weeks of gestation is statistically significant. The trial is expected to complete end 2016 .
Feb 11Makena is the first treatment to be approved by the FDA for prevention of preterm delivery. It is given by a healthcare provider as a weekly intramuscular injection beginning between 16 & 20 weeks of pregnancy .