Characterization of the antithrombotic fingerprint of the branded and copies of the low-molecular-weight enoxaparin using thrombin generation assay.

BACKGROUND

The patent protection of low-molecular-weight heparins (LMWHs) expired, so the definition of criteria for the biological similarity between LMWH copies and the original product is a real need.

AIM: The present in vitro study compared copies and branded enoxaparin using the specific anti-Xa activity and the calibrated automated thrombogram assay.

METHODS

Samples of platelet-poor plasma (PPP) and platelet-rich plasma (PRP) from 15 healthy volunteers were spiked with branded enoxaparin (Lovenox) or its copies (Cutenox, Dilutol, Enoxa, Fibrinox, Loparin, Lupenox, Novex, Noxprin, and Versa). The specific anti-Xa activity was measured in PPP, and thrombin generation was assessed in PPP and PRP in the presence of tissue factor or pancreatic cancer cells BXPC3.

RESULTS

The anti-Xa activity of enoxaparin copies ranged from 0.072 to 0.088 IU/μg, being lower as compared to the branded enoxaparin (0.095 anti-Xa IU/μg). The potency of each copy to inhibit thrombin generation varied in the 3 experimental systems. The presence of platelets or pancreatic cancer cells BXPC3 in human plasma induced significant modifications in the inhibitory efficiency of enoxaparin copies on thrombin generation, which distinguished them from the branded product.

CONCLUSION

Enoxaparin copies showed significant variability regarding their inhibitory potency on thrombin generation. Platelets and cancer cells significantly increased the variability of the antithrombotic efficiency of the copies as compared to the branded enoxaparin. The present study underlines the need for the elaboration of additional functional criteria to evaluate the global antithrombotic capacity of enoxaparin copies in order to evaluate their potential sameness with the branded drug.