Enoxaparin Biosimilar Shows Similar Efficacy to Originator in Preventing Postoperative Subclinical Thrombosis

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The biosimilar Enoxa (enoxapain biosimilar, Medis Pharmaceuticals), marketed in Tunisia, demonstrated equivalence in preventing subclinical postoperative thrombotic events in patients with digestive cancers to Sanofi’s Lovenox, in a randomized controlled trial published in PLOS ONE.

Both cancer and major surgery increase the risk of venous thromboembolic disease (VTED), including deep vein thrombosis and pulmonary embolism: cancer induces hypercoagulability, and surgery causes vascular injury that is often followed by a period of immobilization. VTED is the second leading cause of death in patients with cancer, the authors noted.

Thromboprophylaxis reduces the risk of VTED following surgery, and several molecules for this purpose are available, including enoxaparin, a low-molecular weight heparin (LMWH). Multiple biosimilar enoxaparin products are available, including Inhixa and Thorinane in the EU, Fragmin and Innohep in the US, and Cloti-Xa in India. Enoxa has been available in Tunisia since 2007.

This randomized controlled trial in a single center in Tunisia evaluated equivalence of Enoxa to the reference product in patients following surgery for digestive cancers. Patients received one injection of either originator or biosimilar enoxaparin daily for 30 days starting 8-12 hours after surgery. The primary outcome of the study was asymptomatic thromboembolic events assessed by Doppler ultrasound of the lower limbs 7-10 days following surgery, and secondary endpoints included symptomatic thrombotic events, heparin-induced thrombocytopenia, bleeding events, and deaths. A total of 168 patients were enrolled, and 145 patients were evaluated by Doppler ultrasound, 74 in the biosimilar group and 71 in the reference product group.

There were no statistically significant differences between groups for demographics and thrombosis-associated factors, such as history of cardiovascular disease and stroke, or use of hormone replacement therapy.

Six (4.1%) of the 168 enrolled patients had subclinical venous thrombosis following surgery, 2 (2.7%) in the biosimilar group and 4 (5.6%) in the originator group. The 95% CI of the difference in means between groups (-0.095 to 0.036) fell within the margins of equivalence (-0.20 to 0.20).

Clinical and subclinical events combined occurred in 6 (6.9%) and 7 (8.6%) patients in the biosimilar and reference product groups, also with no significant difference between groups. There were also no significant differences in other secondary outcomes, such as postoperative bleeding, heparin-induced thrombocytopenia, post-operative complications, and deaths. The authors noted the overall mortality rate (10.1%) was high. However, it was not significantly different between groups. Deaths occurred in 12.6% of patients who received the biosimilar and 7.4% in those who received the reference product.

The authors concluded Enoxa met equivalence criteria, and noted their results are consistent with 2 non-comparative studies that found Enoxa was safe and effective for preventing thrombotic events in patients undergoing total hip replacement. To their knowledge, theirs is the first trial to compare Enoxa to the reference product for preventing post-operative, subclinical thrombotic events.

Reference

Dziri C, Ben Hmida W, Dougaz W, Khalfallah M, Samaali I, Jerraya H, Bouasker I, Nouira R. Biosimilar versus branded enoxaparin to prevent postoperative venous thromboembolism after surgery for digestive tract cancer: Randomized trial. PLoS One. 2023;18(11):e0293269. doi:10.1371/journal.pone.0293269