Abelacimab

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 Cost-effectiveness analysis based upon the results from the landmark AZALEA-TIMI 71 study which was stopped early by the Data Monitoring Committee (DMC) due to a substantially greater than anticipated reduction in major and clinically relevant non-major bleeds in the abelacimab arms compared to rivaroxaban Abelacimab is an investigational, once-monthly, highly selective, fully human monoclonal antibody that achieves a near complete 99% Inhibition of Factor XI CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Results of the first-ever cost-effectiveness study of a Factor XI inhibitor were presented today during sessions of the Professional Society for Health Economics and Outcomes Research (ISPOR) annual meeting. The analysis indicates that abelacimab could offer a potential cost-savings of $50,000 USD and improvements of 1.5 quality-adjusted life years (QALY’s) per person over a lifetime horizon as compared to rivaroxaban, a commonly used direct oral anticoagulant (DOAC). If approved by US regulatory authorities, abelacimab could be a highly cost-effective anticoagulant option. “The objective of our economic analysis was to explore the potential cost-effectiveness of abelacimab versus rivaroxaban, using the results from the AZALEA-TIMI 71 study that were presented during a late-breaking session at the 2023 American Heart Association Scientific Sessions,” explained Josephine Li-McLeod, RPh, PhD, at Stratevi, an independent health economics and outcomes research consulting firm, who developed the modeling and led the assessment. “The results from this early economic analysis clearly indicate that abelacimab was dominant versus rivaroxaban with significant savings and a greater number of quality-adjusted life years, meaning it could be a very cost-effective anticoagulant option for patients with atrial fibrillation at moderate-to-high risk of stroke.” Despite the effectiveness of current anticoagulants in stroke prevention, concerns about bleeding risk for patients taking anticoagulants persist. So much so that the underuse of anticoagulants in patients with atrial fibrillation (AF) at risk for stroke is one of the greatest public health issues facing cardiovascular patients.1 “The reality is too many patients with atrial fibrillation are either not taking an anticoagulant at all, or are using a sub-therapeutic dose, typically due to the risk or fear of bleeding associated with currently available therapies. The great promise of a factor XI inhibitor such as abelacimab, rests largely with the ability to prevent thrombosis with minimal disruption of hemostasis. In doing so, this class could represent a major paradigm shift in how we best manage patients in the future,” said Dan Bloomfield, MD, Chief Medical Officer at Anthos Therapeutics. “The significantly improved bleeding pro abelacimab as seen in the AZALEA-TIMI 71 study, coupled with the results from this new cost-effectiveness analysis means that, if approved, patients may have a safer, cost-saving treatment alternative as compared to a standard of care direct-oral anticoagulant.” About Abelacimab Abelacimab is a novel, dual-acting, once-monthly-administered fully human investigational monoclonal antibody that binds to FXI preventing its activation and also neutralizes FXIa activity.2 As a monoclonal antibody, abelacimab is not metabolized via the cytochrome P450 system or as a substrate for P-glycoprotein, meaning the risk of drug-drug interactions is very low. There is no need to adjust the dose based on age or renal/hepatic status. Factor XI inhibition offers the promise of hemostasis-sparing anticoagulation for the prevention and treatment of arterial and venous thromboembolic events.3 Abelacimab is the only Factor XI inhibitor being studied for both conditions. In patients with atrial fibrillation, abelacimab is planned to be dosed subcutaneously (SC) monthly to maintain near-complete inhibition in a chronic setting. It is also planned to be administered via an initial intravenous (IV) infusion for acute indications requiring immediate onset of action and then followed by subsequent monthly SC administration. In the AZALEA-TIMI 71 study, abelacimab 150 mg dosed subcutaneously once-monthly, inhibited Factor XI by 99%.3 In a PK / PD study, abelacimab administered IV provided profound suppression of Factor XI within one hour after the start of therapy and maintained near maximal inhibition for up to 30 days.4 In a Phase 2 study published in the New England Journal of Medicine in 2021, a single intravenous dose of abelacimab after knee surgery reduced the rate of venous thromboembolism by 80%, measured 10 days after surgery, compared to enoxaparin.5 Abelacimab received a Fast Track Designation from the FDA in July 2022 for the treatment of thrombosis associated with cancer. In September 2022, abelacimab was also granted a Fast Track Designation for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Abelacimab is an investigational agent and is not approved for any indication in any country. About the Cost-Effectiveness Model A previously developed Markov state-transition cohort model reflecting the clinical pathways typical of people with AF at moderate-to-high risk of stroke was revised to assess the cost-effectiveness of abelacimab versus rivaroxaban from the US payer perspective.6,7 Clinical inputs were derived from prior models and the AZALEA-TIMI 71 trial.6,7,8 In scenario analyses, the value-based price of abelacimab was explored at various willingness-to-pay (WTP) thresholds using the 95% confidence interval (CI) of the primary bleeding endpoint from AZALEA-TIMI 71. Cost and utility estimates were derived from literature and publicly available sources. Because AZALEA-TIMI 71 was a safety study, the model assumed no difference in the risk of stroke or MI between abelacimab and rivaroxaban.8 The model used a 3-month cycle length and a lifetime horizon. All costs were inflation-adjusted to 2023 US dollars (USD). Following economic model guidelines, a 3% annual discount rate was applied to both cost and utilities.9 All model parameters were varied ±20% in one-way sensitivity analyses to evaluate cost-effectiveness sensitivity. About the AZALEA-TIMI 71 Study The AZALEA-TIMI 71 study was an event-driven, randomized, active-controlled, blinded endpoint, parallel-group study with a primary endpoint that evaluated the effect of two blinded doses of abelacimab relative to open-label rivaroxaban in patients with atrial fibrillation (AF) who are at moderate-to-high risk of stroke. The primary endpoint of the AZALEA-TIMI 71 study was the composite of the rate of major or clinically relevant non-major bleeding events. A secondary endpoint was major bleeding on its own. Patients were randomized 1:1:1 and administered subcutaneous (SC) abelacimab 150 mg once-monthly, abelacimab 90 mg once-monthly, or rivaroxaban 20 mg daily. With a median follow-up of 21 months, spanning more than 2,000 patient-years, the AZALEA-TIMI 71 study is the largest and longest head-to-head study of a Factor XI inhibitor to provide definitive evidence of a highly significant reduction in bleeding as compared to a standard-of-care anticoagulant. Summary of Results as Presented During the American Heart Association 2023 Scientific Sessions:8 Primary endpoint met with a 67% reduction in major or clinically relevant non-major bleeding (CRNM) with abelacimab 150 mg compared with rivaroxaban 20 mg in patients with atrial fibrillation who are at moderate-to-high risk of stroke (P<0.001, HR 0.33, 95% Cl 0.19–0.55) 74% reduction in major bleeding alone with abelacimab 150 mg vs rivaroxaban 20 mg (P=0.002, HR 0.26, 95% CI 0.11-0.61) 93% reduction in gastrointestinal (GI) bleeding with abelacimab 150 mg vs rivaroxaban 20 mg (P=0.008, HR 0.07, 95% Cl 0.01-0.50) 51% reduction in net clinical outcome with abelacimab 150 mg vs rivaroxaban 20 mg (P<0.001, HR 0.49, 95% CI 0.33-0.71) Factor XI inhibition of ~99% with abelacimab 150 mg dosed once monthly The AZALEA-TIMI 71 study enrolled 1,287 patients across 95 global study sites including the U.S. and Canada, Europe and Asia. The independent data monitoring committee (IDMC) recommended that the study end early because of a substantially greater than anticipated reduction in major and clinically relevant non-major bleeding in the abelacimab arms compared to rivaroxaban and a benefit:risk ratio that favored abelacimab. At the same time, the IDMC also recommend that an optional open-label extension period should be made available. AZALEA-TIMI 71 Open-Label Extension An optional extension period in order to provide longer-term data was included as part of the AZALEA-TIMI 71 study protocol. It could be initiated if the independent data monitoring committee (IDMC) stopped the study early due to an imbalance of bleeding substantially favoring abelacimab over rivaroxaban, and the benefit:risk clearly favored abelacimab. Investigative sites had the option of participating or not participating in the extension period. Patients who completed the end-of-treatment visit on study treatment and met the eligibility criteria for the extension period had the option to participate or not. About Atrial Fibrillation Also known as AF, or AFib, atrial fibrillation is an irregular heartbeat, or arrhythmia that can lead to blood clots, is a preventable cause of stroke, and a leading cause of long-term disability and mortality.10,11 Approximately 37 million people worldwide are currently diagnosed with atrial fibrillation,12 while in the United States, the Centers for Disease Control and Prevention (CDC) estimates that more than 12 million Americans will develop AF by 2030.13 The goal of anticoagulation therapy is to prevent and/or treat thrombosis with minimal disruption of hemostasis. Despite the effectiveness of current anticoagulants in stroke prevention, concerns about bleeding risk persist. The underuse of stroke prevention in patients with AF at risk for stroke is one of the greatest public health issues facing cardiovascular patients.1 About Anthos Therapeutics Anthos Therapeutics was founded by Blackstone Life Sciences in 2019 and obtained from Novartis Pharma AG the exclusive global rights to develop, manufacture, and commercialize abelacimab. Anthos Therapeutics is a clinical-stage biopharmaceutical company focused on the development and commercialization of genetically and pharmacologically validated innovative therapies to advance care for high-risk cardiovascular patients. For more information, visit the Company’s website and follow on Twitter and LinkedIn. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the initiation, and timing, of future clinical trials and its research and development. All statements, other than statements of historical facts, contained in this press release, including statements regarding the company’s strategy, future operations, future financial position, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “become,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. In addition, the forward-looking statements included in this press release represent the company’s views as of the date hereof and should not be relied upon as representing the company’s views as of any date subsequent to the date hereof. The company anticipates that subsequent events and developments will cause the company’s views to change. However, while the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so. [1] Pokorney SD, et al. Am Heart J. 2019;210:29-38. [2] David Gailani, Andras Gruber. Blood 2024 ( ) [3] Hsu et al. J Am Coll Cardiol. Aug. 2021 ( ) [4] Yi BA et al. J Thromb Haemost. Oct. 2021 ( ) [5] Verhamme P et al. New Engl J Med July 2021 ( ) [6] Sterne JA, et al. Health Technol Assess. 2017;21(9):1-386 [7] Benner J, et al. Value in Health. 2023;26(6):S122. 2 [8] Ruff CT, AZALEA-TIMI 71 Steering Committee & Investigators. AZALEA-TIMI 71. A Multicenter, RandomiZed, Active-ControLled Study to Evaluate the Safety and Tolerability of Two Blinded Doses of Abelacimab Compared with Open-Label Rivaroxaban in Patients with Atrial Fibrillation. Presented at: American Heart Association Scientific Session; November 12, 2023; Philadelphia, PA, USA. [9] Sanders GD, et al. JAMA. 2016;316(10):1093-1103. [10] January CT, et al. J Am Coll Cardiol. 2019;74(1):104-132 [11] Hindricks G, et al. Eur Heart J. 2021;42(5):373-498. [12] Lippi G et al. Int J Stroke 2021;16(2):217-221. [13] Center for Disease Control and Prevention website; Atrial Fibrillation page ( ) View source version on businesswire.com: Contacts Media: Caren Begun TellMed Strategies 908-947-0500 x723 caren.begun@tmstrat.com Source: Anthos Therapeutics View this news release online at:

Bayer is stopping a pivotal clinical trial for its experimental treatment for atrial fibrillation at the recommendation of an independent committee that concluded the drug would not be more effective than a Bristol Myers Squibb and Pfizer product widely used to treat the heart condition. The Bayer drug, asundexian, was being evaluated in a Phase 3 study enrolling patients with atrial fibrillation who are at risk of stroke. The once-daily drug is an oral small molecule designed to block Factor XIa, a protein in the coagulation cascade. The irregular heartbeat caused by afib leads to poor blood flow that raises the risk of blood clots or stroke. Drugs available to treat the condition also causes bleeding. By targeting Factor Xia, Bayer hoped its drug would prevent stroke without also leading to the bleeding complications of currently used therapies. The Phase 3 study, OCEANIC-AF, compared asundexian to Eliquis, a blood-thinning drug from BMS and Pfizer that works by blocking a different clotting protein called FXa. Bayer said its drug’s safety was consistent with earlier tests but it provided no specific details about the lack of efficacy conclusion reached by the independent data monitoring committee. The company did say that the committee recommends continuing OCEANIC-STROKE, a separate placebo-controlled Phase 3 test of the drug for the prevention of ischemic stroke. “Although the results from this analysis do not support the continuation of the OCEANIC-AF study, we will continue investigating asundexian in the OCEANIC-STROKE study and are currently reevaluating other indications in patients in need of antithrombotic treatment,” Christian Rommel, member of the executive committee of Bayer’s Pharmaceutical Division and global head of research and development, said in a prepared statement. The bleeding risks associated with currently available afib therapies have led companies to try to develop safer alternatives. BMS is among them, having reached Phase 3 testing with its Factor X1a inhibitor, milvexian. In a note sent to investors Monday, William Blair analyst Matt Phipps wrote that the failure of Bayer’s drug will affect investor confidence in the ability of Factor XIa inhibitors to top Eliquis in atrial fibrillation. Milvexian is expected to post Phase 3 results in 2027. Privately held Anthos Therapeutics reached Phase 2 testing with its Factor XI inhibitor, an antibody called abelacimab. During the American Heart Association’s meeting earlier this month, the company reported the early stoppage of that drug’s mid-stage study—a move prompted by greater than expected efficacy. Anthose said its drug led to a 67% lower risk of bleeding compared to Johnson & Johnson Factor Xa inhibitor, Xarelto. Phipps said comparisons across the trials are difficult without any standardized assays, but he noted that Anthos reported a sustained 99% reduction of Factor XIa compared to roughly 90% inhibition of Factor XIa activity for Bayer’s asundexian at trough levels in the blood. That indicates it’s possible Bayer’s drug was underdosed in its trials, particularly as monotherapy, Phipps said. By contrast, BMS has tested a wider range of doses, including once-daily and twice-daily dosing. BMS is testing a 100 mg dose of milvexian twice daily as a monotherapy in atrial fibrillation, but a 25 mg twice-daily dose on top of platelet inhibitors in secondary stroke prevention or acute coronary syndrome patients, Phipps said. Bayer said it will further analyze the Phase 3 data for its drug to better understand what happened in the afib study. The company also plans to publish the data.