First Cost-Effectiveness Analysis Shows Abelacimab Could Save Costs Over Current Anticoagulant

Treatment with abelacimab could result in potential cost-savings of $50,000 over a lifetime per patient basis and higher quality-adjusted life years in atrial fibrillation patients at a high risk of stroke versus rivaroxaban. This cost-effectiveness analysis is based on the significant findings from the AZALEA-TIMI 71 study, which was halted early by the Data Monitoring Committee due to a significantly greater than anticipated reduction in major and clinically relevant non-major bleeding in the abelacimab arms compared to rivaroxaban.

Abelacimab is an investigational, once-monthly, highly selective, fully human monoclonal antibody that achieves near complete 99% inhibition of Factor XI.

Results from the first-ever cost-effectiveness study of a Factor XI inhibitor were presented at the Professional Society for Health Economics and Outcomes Research (ISPOR) annual meeting. The analysis suggests that abelacimab could potentially save $50,000 USD per person and increase quality-adjusted life years (QALYs) by 1.5 over a lifetime compared to rivaroxaban, a widely used direct oral anticoagulant (DOAC). If approved by US regulatory authorities, abelacimab could emerge as a highly cost-effective anticoagulant for patients with atrial fibrillation at moderate-to-high risk of stroke.

Josephine Li-McLeod, RPh, PhD, from the independent health economics and outcomes research consulting firm Stratevi, noted that their economic analysis aimed to evaluate the cost-effectiveness of abelacimab versus rivaroxaban using the results from the AZALEA-TIMI 71 study. The findings from this early economic study indicated that abelacimab was dominant over rivaroxaban, with significant savings and increased QALYs. This suggests that abelacimab could be a cost-effective option for atrial fibrillation patients at risk of stroke.

Despite the efficacy of current anticoagulants in preventing strokes, concerns about bleeding risks remain. This has led to the underuse of anticoagulants in patients with atrial fibrillation at risk of stroke, posing a significant public health challenge. Dan Bloomfield, MD, Chief Medical Officer at Anthos Therapeutics, highlighted that many atrial fibrillation patients either do not take anticoagulants or use sub-therapeutic doses due to bleeding risks associated with current therapies. The potential of factor XI inhibitors like abelacimab lies in their ability to prevent thrombosis with minimal impact on hemostasis, potentially revolutionizing patient management.

Abelacimab is a novel, once-monthly, fully human monoclonal antibody that prevents the activation of FXI and neutralizes FXIa activity. It is not metabolized via the cytochrome P450 system, reducing the risk of drug-drug interactions, and there is no need for dose adjustment based on age or renal/hepatic status. Abelacimab aims to achieve hemostasis-sparing anticoagulation for preventing and treating arterial and venous thromboembolic events.

In atrial fibrillation patients, abelacimab is planned to be administered subcutaneously (SC) once a month to maintain near-complete inhibition in a chronic setting. For acute conditions requiring immediate action, an initial intravenous (IV) infusion followed by monthly SC administration is intended.

The AZALEA-TIMI 71 study showed that abelacimab 150 mg SC once-monthly inhibited Factor XI by 99%. An IV administration study demonstrated profound suppression of Factor XI within one hour and maintained near-maximum inhibition for up to 30 days. A Phase 2 study published in 2021 indicated that a single IV dose of abelacimab post-knee surgery significantly reduced venous thromboembolism by 80% compared to enoxaparin.

Abelacimab has received Fast Track Designation from the FDA for treating thrombosis associated with cancer and for preventing stroke and systemic embolism in atrial fibrillation patients. It remains an investigational agent not yet approved for any indication.

A Markov state-transition cohort model was used to assess the cost-effectiveness of abelacimab versus rivaroxaban from the US payer perspective. Clinical inputs were derived from previous models and the AZALEA-TIMI 71 trial, and the model assumed no difference in stroke or MI risk between abelacimab and rivaroxaban. The model employed a 3-month cycle length and a lifetime horizon, with all costs adjusted to 2023 USD and a 3% annual discount rate applied to both cost and utilities. Sensitivity analyses varied all model parameters by ±20% to evaluate cost-effectiveness sensitivity.

The AZALEA-TIMI 71 study, the largest and longest head-to-head study of a Factor XI inhibitor, enrolled 1,287 patients across 95 global sites. The study was ended early due to a significant reduction in bleeding in the abelacimab arms compared to rivaroxaban and a favorable benefit-risk ratio for abelacimab. An optional open-label extension period was offered to provide longer-term data.