Medicure Inc., a specialty pharmaceutical company, announced that it has received a Complete Response Letter from the US Food and Drug Administration (FDA) for its supplemental New Drug Application (sNDA) requesting an expanded indication for patients presenting with ST segment elevation myocardial infarction (STEMI).
The FDA issued a Complete Response Letter to communicate that its initial review of the application is complete; however, it cannot approve the application in its present form and requested additional information. The On-TIME 2 trial provided the majority of supporting information for the sNDA submission. Medicure will work directly with the FDA to address these comments.
The efficacy and safety of the Aggrastat high-dose bolus (HDB) regimen has been evaluated in more than 30 clinical studies involving over 15,000 patients and is currently recommended in the ACCF/AHA/SCAI Guidelines. The STEMI indication for Aggrastat HDB was approved in Europe based substantially on the same clinical data submitted in the company's sNDA. As of now, none of the marketed Glycoprotein IIb/IIIa Inhibitors (GPI) are approved for STEMI in the United States.
"We are evaluating the FDA's response and will work closely with the Agency to address their comments," stated Dr. Albert Friesen, chief executive officer and president of Medicure Inc. "In the meantime, Aggrastat continues to be the fastest growing GPI in the United States."
The On-TIME 2 trial was a multi-center, prospective, randomized, controlled clinical trial which was designed to assess the effect of Aggrastat using the HDB regimen (25 mcg/kg followed by a 0.15 mcg/kg/min maintenance infusion) in patients with STEMI planned for primary PCI. All patients received ASA, a 600 mg loading dose of clopidogrel, and unfractionated heparin. The study was completed in two phases: a pilot, open label phase (n=414) followed by a larger double-blind phase (n=984). A pooled analysis of data from both phases was pre-specified to evaluate the effect of the Aggrastat HDB regimen compared to control as measured by a primary endpoint defined as the 30-day MACE rate (death, recurrent MI and uTVR). In this pooled analysis, MACE at 30 days was significantly reduced by initiation of Aggrastat compared to control (5.8% vs. 8.6%; p=0.043). The clinical benefit seen in the primary PCI population at 30 days was sustained at one year, as results indicated a significantly lower total mortality (2.4% vs. 5.5%, p=0.007) and cardiac mortality rate (1.4% vs. 4.3%, p=0.003) associated with Aggrastat versus the control arm. In patients receiving a stent, the incidence of early (0–30 days) stent thrombosis was 2.1 vs. 5.2% (p = 0.006) in the Aggrastat and control group, respectively, which was driven by a reduction in the incidence of acute (0–24 h) stent thrombosis between the two treatment groups (0.2% vs. 3.0%; p < 0.001). The incidence of 30-day mortality was significantly reduced in patients receiving Aggrastat compared to control (1.0% vs. 3.1%; p = 0.02, respectively) among patients undergoing primary PCI and receiving a stent.