Biosimilars in the Prophylaxis of Venous Thromboembolism

In recent years, several biologically similar products (biosimilars) have appeared in this therapeutic group, which are increasingly used in clinical practice. Before a biosimilar product is introduced to the market, studies must be conducted to demonstrate therapeutic equivalence with the original product. In these studies, the physicochemical, functional, and pharmacodynamic properties of both drugs are compared. After being brought to market, biosimilar products are further closely monitored for potential new safety signals or immunogenicity. However, results regarding their efficacy and safety in real-world clinical practice are also essential.

The First Biosimilar Enoxaparin Inhixa was approved for use by the European Medicines Agency (EMA) in 2016. It is indicated for adults:

• For the prevention of VTE in patients at moderate or high risk in surgery (especially orthopedic or general, including oncological);
• For the prevention of VTE in internal patients with acute illness (e.g., acute heart failure, respiratory failure, severe infections, or rheumatic diseases), reduced mobility, and increased risk of VTE;
• For the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) – except for PE that is likely to require thrombolytic therapy or surgery;
• For the extended treatment and prevention of recurrence of DVT and PE in patients with active cancer;
• For the prevention of thrombus formation in the extracorporeal circulation during hemodialysis;
• In acute coronary syndrome:
  • For the treatment of unstable angina and non-ST-elevation myocardial infarction (NSTEMI) in combination with oral acetylsalicylic acid;
  • For the treatment of acute ST-elevation myocardial infarction (STEMI), including patients for whom conservative treatment is planned or those undergoing subsequent percutaneous coronary intervention (PCI).

Efficacy and Safety Assessment in Real-World Practice A retrospective observational study from two Italian centers evaluated the efficacy and safety of biosimilar enoxaparin Inhixa in preventing VTE in real-world clinical practice among patients hospitalized for internal diseases or after abdominal surgery. Data from 189 patients admitted to the internal medicine department of the hospital in Varese between June and November 2018 and 192 patients who underwent major abdominal surgery in a Milan hospital from July 2018 to January 2019 were analyzed. Inhixa was administered to both groups for VTE prophylaxis during the entire hospital stay.

The average age of internal patients was 75 years (52% women), with 20% being fully immobilized and 20% having reduced mobility. Thromboprophylaxis was most often administered due to acute infection (68%), followed by heart (15%) or respiratory (6%) failure, and stroke (5%).

In the surgical patient group, the average age was 63 years (52% women), and the majority of patients (67%) had no mobility limitations. Only 1.6% of patients were fully immobilized. The most common surgical indication was cholelithiasis (40%), 18% of patients had liver tumors (primary or metastatic), and 16% underwent surgery for bowel cancer.

Low Incidence of Bleeding and VTE A major bleeding episode occurred in 1.8% (95% confidence interval [CI] 0.7–3.8) of the total study population, with 1.6% in hospitalized internal patients and 2.1% from the surgical department.

Symptomatic, objectively documented VTE occurred in 0.5% (95% CI 0.1–1.9) of patients, with the same incidence among internal and post-surgical patients.

These data were compared to a pooled analysis of data from 25 available studies with the original enoxaparin. In this analysis, the incidence of major bleeding episodes in internal patients was 0.5% (95% CI 0.2–1.1) and 2.6% (95% CI 1.3–5.1) in patients after abdominal surgery. The incidence of VTE during prophylaxis with the original product was 0.6% (95% CI 0.2–1.8) in internal patients and 0.7% (95% CI 0.3–1.6) in surgical patients.

Conclusion Since 2016, the first biosimilar enoxaparin, Inhixa, has been registered. Data from an observational Italian study showed a low incidence of bleeding episodes and VTE with its prophylactic use in both internal and surgical patients. These findings were comparable to the results of pooled analysis data from clinical trials with the original enoxaparin in a corresponding patient population. Real-world data thus support the use of biosimilar enoxaparin as a valid alternative to the original product.

Sources:

1. SPC Inhixa. Available at: www.ema.europa.eu/cs/documents/product-information/inhixa-epar-product-information_cs.pdf
2. Fantoni C., Bertù L., Faioni E. M. et al. Safety and effectiveness of biosimilar enoxaparin (Inhixa) for the prevention of thromboembolism in medical and surgical inpatients. Intern Emerg Med 2021; 16 (4): 933–939, doi: 10.1007/s11739-020-02536-4.