Comparison of regulatory, quality and clinical aspects of available LMWH biosimilars may be helpful for their selection and uptake
Abstract published: August 2021
With at least 8 branded low-molecular weight heparins (LMWH) internationally available, which LMWH biosimilar should be kept in formulary?
Although nowadays largely superseded in clinic by direct-acting oral anticoagulants, LMWH, such as enoxaparin, remain drugs of choice for cancer patients at risk of venous thromboembolism and for prophylaxis during pregnancy and are widely prescribed.
In the USA, follow-on LMWH products are considered generics, whereas in the EU they are considered biosimilars. The EMA approval process for new LMWH biosimilar applications specifies a number of non-clinical and clinical studies be conducted – the former including quality comparisons and the latter at least a pharmacodynamics study looking at anti-FXa and anti-FIIa activity (monitoring anti-coagulant therapy) and release of tissue factor pathway inhibitor (TFPI) in healthy volunteers. A dedicated comparative efficacy trial is not necessary, although safety and immunogenicity assessment in patients is mandatory. As with all approved biosimilars, a pharmacovigilance/risk management plan is required within the EMA’s authorization procedure.
Most LMWH products are prepared from porcine intestinal-derived unfractionated heparin, which is partially depolymerized to the required molecular weight. The depolymerization process can be achieved by several means – resulting in small, structural differences among the various LMWH generics/biosimilars. However, all these products are approved for the same indications.
Three biosimilarity studies for enoxaparin have been conducted, and all concluded the products were bioequivalent. Moreover, pharmacovigilance for LMWH biosimilars in the EU has not led to any safety signals.
So, which LMWH should be stocked in formularies? A group of Dutch clinical pharmacists and researchers from Queen’s University Belfast have devised a model for formulary uptake decisions termed System of Objectified Judgment Analysis (www.sojaonline.com). The model provides a system of critical weight factors for Pharmacy and Therapeutic committee voters to assess each available product, with that achieving the highest score recommended for inclusion. This system favors products with modern analytical tests for impurities, phase III clinical data, prophylactic and therapeutic dosage forms available – and an attractive price. For LMWH uptake, this model provides a straightforward, transparent process to enhance policy making.
LMWH remains widely prescribed for cancer patients in need of anti-coagulation therapies. A novel System Objectified Judgement Analysis model has been released which provides a transparent policy-making process for deciding which LMWH biosimilars provide the best cost-benefit and should be stocked in pharmacy formularies.