生物等效性和生物利用度杂志

抽象的

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

Mouna Sassi, Kaouther Beltaief, Habib Haouala, Sondes Kraiem, Samir Kammoun, Faouzi Maatoug, Gouider Jeridi, Mohsen Hassine, Mahdi Methammem, Ibrahim Nciri, Sofiane Kammoun, Mohamed Zilli, Mondher Kortas, Mohamed Habib Grissa, Ismail Elalamy, Wahid Bouida M and Semir Nouira

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.