Research Article
Mouna Sassi, Kaouther Beltai
Abstract
Enoxaparin is a complex, biologically derived low-molecular-weight heparin. The manufacturing process for biologics is complex which makes difficult to obtain exact replicas of the reference biologic. This is why there is a critical need to ensure that generics of biologic medicines are safe and effective. This study was carried out to assess the comparability of a Tunisian generic enoxaparin (Enoxamed®, Unimed Laboratory, Tunisia) with the originator product (Lovenox®; Sanofi US, Bridgewater, New Jersey) through non-clinical in vitro study in healthy volunteers and clinical studies (phases III and IV) in patients with acute coronary syndrome (ACS). For non-clinical study, blood from healthy volunteers was used to compare the effect of both formulations using anti-Xa activity and the thrombin generation test (TGT). All parameters of TGT were analyzed. For clinical studies, ACS patients were randomly assigned to receive Enoxamed® (27 in phase III and 120 in phase IV) or Lovenox® (23 in phase III and 118 in phase IV) and anti-Xa activity was measured 4 h thereafter. In healthy volunteers, the two products inhibited thrombin generation in a concentration-dependent manner. According to the profiles obtained from the TGT, Enoxamed® had similar potency as Lovenox®. In ACS patients, anti-Xa activity was found no difference between Enoxamed® and Lovenox®. No difference in major cardiovascular events was observed at 30 days after initial admission. Our finding combining anti-Xa activity and thrombin generation parameters would support the possibility to translate this biological efficacy to the clinical setting. The generic enoxaparin Enoxamed® showed comparability and then the main regulatory criteria of bioequivalence with the originator product.