Rivaroxaban

75% of patients in the rivaroxaban arm voluntarily switched from the once-daily oral anticoagulant to once-monthly abelacimab Landmark AZALEA-TIMI 71 Study previously stopped early due to an overwhelming benefit favoring abelacimab relative to rivaroxaban across all bleeding endpoints Data Monitoring Committee (DMC) recommended an open-label extension for all eligible patients to benefit from abelacimab treatment Abelacimab is a once-monthly, highly selective, fully human monoclonal antibody that achieves a near complete 99% inhibition of Factor XI CAMBRIDGE, Mass., June 06, 2024 (GLOBE NEWSWIRE) -- Anthos Therapeutics, Inc., a clinical-stage company developing innovative therapies for cardiovascular diseases, founded by Blackstone Life Sciences (BXLS), today provided an update on the transition of patients in the open-label extension (OLE) portion of the AZALEA-TIMI 71 study. When the independent data monitoring committee (DMC) recommended that the study be stopped early because of the substantially greater than anticipated reduction in bleeding events favoring abelacimab over rivaroxaban, they also recommended that an optional open-label extension be made available so that all eligible patients could potentially benefit from abelacimab treatment. “The impressive bleeding reductions with abelacimab in the AZALEA-TIMI 71 study represent a potential game changer for how we treat patients with atrial fibrillation in the future, so it was no surprise when almost 84% of eligible patients, including the vast majority who had been on rivaroxaban during the trial, voluntarily decided to enter the open-label extension to receive abelacimab,” said Dr. Christian T. Ruff, MD, MPH, Principal Investigator of AZALEA-TIMI 71, the Director of General Cardiology at Brigham and Women's Hospital, Senior Investigator of the TIMI Study Group, an Associate Member of the Broad Institute of MIT and Harvard, and an Associate Professor of Medicine at Harvard Medical School. The initial results of the AZALEA-TIMI 71 study1 of patients with atrial fibrillation at moderate-to-high risk of stroke were presented at the American Heart Association 2023 scientific congress during a late-breaking session. For the primary endpoint, abelacimab 150 mg dosed once-monthly, demonstrated a highly significant 67% reduction in major or clinically relevant non-major bleeding.1 In addition, there was a substantial 74% reduction in major bleeding alone and a 93% reduction in gastrointestinal (GI) bleeding, all favoring abelacimab over rivaroxaban, a standard-of-care anticoagulant.1 “We are very pleased that the open-label extension of the AZALEA-TIMI 71 study has completed its transition phase and that the vast majority of eligible patients voluntarily opted to receive abelacimab 150 mg once-monthly moving forward,” said Dr. Dan Bloomfield, Chief Medical Officer of Anthos Therapeutics. “Too many patients with diagnosed atrial fibrillation are not receiving an anticoagulant today or are taking an inappropriate dose, due to the risk or fear of bleeding, the possibility for drug-drug interactions, dosing complications due to age or renal status or just because they forget to take their daily medication. If approved, it is our hope that abelacimab will provide patients with the protection they need against blood clots, but with a placebo-like bleeding profile.” Atrial fibrillation, or AF, is the most common type of irregular heart rhythm. The most severe complication of AF is stroke,2 which can be prevented by taking an anticoagulant, or “blood thinner.” The Centers for Disease Control and Prevention (CDC) estimates that 12.1 million people in the United States will have atrial fibrillation by 2030.3 However, data from multiple patient registries and claims-based data analyses highlight that approximately 40% to 60% of patients with atrial fibrillation are either not on an anticoagulant or are receiving a sub-therapeutic dose and are thereby not benefiting from the protection that anticoagulants provide. This underuse of anticoagulants has been cited as one of the greatest public health issues facing cardiovascular patients.4 About Abelacimab Abelacimab is a highly selective, fully human monoclonal antibody that binds to FXI and locks it in the inactive state, preventing the formation of activated FXI (FXIa). 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.5 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%.1 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.6 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.7 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 AZALEA-TIMI 71 Phase 2 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:1 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 the LILAC-TIMI 76 Phase 3 Study The LILAC-TIMI 76 study is an event-driven, randomized, placebo-controlled, double-blind, parallel-group study to evaluate the efficacy and safety of abelacimab relative to placebo on the rate of ischemic stroke or systemic embolism in patients with atrial fibrillation (AF) who have been deemed to be unsuitable for currently available anticoagulation therapy. Patients in the study will be randomized to receive abelacimab 150 mg subcutaneous (SC) or matching placebo once monthly. The study is targeting to enroll approximately 1,900 patients from more than 400 sites in North America, Europe, Latin America, the Middle East and Asia. 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. Media Contact: Caren Begun TellMed Strategies 908-947-0500 x723 caren.begun@tmstrat.com 1 TIMI Study Group website; AZALEA-TIMI 71 page ( ) 2 American Heart Association website; Atrial Fibrillation page ( ) 3 Center for Disease Control and Prevention website; Atrial Fibrillation page ( ) 4 Pokorney et al, American Heart Journal, April 2019 ( ) 5 Hsu et al. J Am Coll Cardiol. Aug. 2021 ( ) 6 Yi BA et al. J Thromb Haemost. Oct. 2021 ( ) 7 Verhamme P et al. New Engl J Med July 2021 ( )

Pictured: Bayer and BMS buildings/iStock, Detlef Voigt, JHVEPhoto During the first quarter of the 2024 earnings season, large drugmakers Bayer and Bristol Myers Squibb announced thousands of layoffs in two of the largest workforce reductions so far this year. Coming off years of upheaval in the biotech and pharma sectors, will this be a temporary bump in the road or the beginning of a significant wave of Big Pharma layoffs? In late April, BMS announced a sweeping “strategic productivity initiative” intended to generate approximately $1.5 billion in cost savings through 2025, including eliminating approximately 2,200 jobs this year while prioritizing the development of its key growth brands. BMS’ restructuring efforts come as the pharma sustained a 6% drop in Q1 sales of its lung cancer therapy Opdivo. Meanwhile, Bayer just announced a headcount reduction of around 1,500 positions, mostly in management, as the company was hit with a slight drop in sales and lowered its full-year earnings outlook. The layoffs are meant to help Bayer hit its target of €500 million ($540 million) in sustainable cost savings in 2024 and €2 billion ($2.16 billion) in 2026. Graig Suvannavejh, the senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, told BioSpace that Big Pharma has to show earnings growth, and one way to do that is by increasing revenue or cutting costs. As the larger drug companies look at their five-year forecasts, Suvannavejh contends, “they’re saying to themselves, well, we don’t want to say to investors that our earnings are going to be flat for the next five years because who would want to invest in a company with flat earnings? What do you do? You lay off people.” Another potential challenge looming on the horizon is patent expirations for large drugmakers. These include BMS’ anti-coagulant Eliquis and the cancer treatment Opdivo, which will both expire in 2026 and Bayer’s blood clot prevention drug Xarelto, which is set to expire in August this year. “For many of the largest pharmaceutical companies, they’ve got really big patent expirations or losses of exclusivity,” Suvannavejh said. Large Players, Big Problems While Bayer and BMS have not provided additional details on their job cuts, other actions by large drugmakers provide a window into how they may proceed. Last year, Pfizer launched a cost-cutting initiative toward generating around $3.5 billion in savings through 2024, including an unspecific number of layoffs. The pharma axed 200 employees from its Kalamazoo, Michigan, manufacturing plant that produced its COVID-19 products. Pfizer also made around 500 cuts at its facility in Sandwich, U.K., 120 in Washington State and 285 at its campus in Pearl River, New York, among other layoffs in Ireland, Connecticut, North Carolina and Colorado. Meanwhile, Novartis announced in April that it is continuing its layoffs as it plans to eliminate around 680 jobs in its product development sector over the next two to three years. According to Reuters, around 440 jobs in product development are based in Switzerland, while another 240 are in the U.S.—but these are separate from a restructuring that could result in the loss of around 8,000 jobs. A Novartis spokesperson told BioSpace at the time that many jobs will be moving to other “hubs over the next two years and [the company] will have a 1% to 2% reduction of its global workforce.” Aurojyoti Bose, the lead business fundamentals analyst at GlobalData, told BioSpace that several companies initiated layoffs in 2023, which have continued into 2024. “These layoffs affected employees across various departments such as sales, research & development and product development. Companies implemented these job cuts as part of strategic restructuring efforts aimed at enhancing margins,” Bose said in an email. “Reasons cited for the layoffs included poor sales performance, financial losses, unsuccessful clinical trials, a shift in focus towards specific areas and the closure of facilities.” As for why the companies might be seeing financial losses, expiring patents are a big factor. Between now and 2030, blockbuster drugs are set to fall off patent, putting tens of billions of dollars in sales at risk. Certainly, this factor is on the minds of Bayer executives, with the company warning in its Q1 financial results that the company is already feeling the pressure from generic competition for Xarelto. CFO Wolfgang Nickl said Bayer is expecting Xarelto’s headwinds to increase throughout 2024, with year-on-year sales declines over the next three quarters. Apart from the patent cliffs, Suvannavejh sees artificial intelligence potentially playing a role in future layoffs at Big Pharma as machine learning and other AI tools may be used to “optimize cost structures.” Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.