Comparability of “Enoxamed” a Tunisian Generic Enoxaparin with the Originator Product: Non-clinical and Clinical Studies

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.