Novartis to Acquire Anthos Therapeutics for $3.1 Billion to Advance Abelacimab, a Novel Anti-Thrombotic Monoclonal Antibody

On February 11, 2025, it was reported that Novartis announced the acquisition of Anthos Therapeutics (hereinafter referred to as Anthos), a private clinical-stage biopharmaceutical company headquartered in Boston. Anthos owns Abelacimab (Abelacimab), a late-stage drug under development for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

Novartis will pay an upfront payment of $925 million upon completion of the transaction, subject to certain customary adjustments, with the potential for up to an additional $2.15 billion payable upon the achievement of specified regulatory and sales milestones, bringing the total to $3.1 billion. The transaction is expected to close in the first half of 2025, subject to customary closing conditions.

According to the official announcement by Novartis, this transaction fully aligns with Novartis' growth strategy and therapeutic focus, leveraging the company’s strengths and expertise in the cardiovascular field.

Anthos Therapeutics was founded in 2019 as a joint venture between Blackstone Life Sciences and Novartis. It is a clinical-stage biopharmaceutical company focused on the treatment of cardiovascular diseases. Notably, Anthos Therapeutics holds the global exclusive rights licensed from Novartis for the development, manufacturing, and commercialization of its core product, Abelacimab.

Abelacimab is a novel, highly selective, fully human monoclonal antibody that tightly binds to coagulation factor XI, preventing its activation, thereby simultaneously inhibiting both coagulation factor XI and its activated form, coagulation factor XIa, to prevent thrombosis. The drug provides protection by mimicking the natural state of coagulation factor XI deficiency, while avoiding the bleeding risks commonly associated with traditional anticoagulant drugs.

A proof-of-concept study published in The New England Journal of Medicine in 2021 showed that, compared with the standard control drug, Abelacimab reduced venous thromboembolism (VTE) by approximately 80% in patients. In July 2022, Abelacimab was granted Fast Track designation by the FDA for the treatment of cancer-associated thrombosis. In September of the same year, the drug received Fast Track designation again for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

According to statistics, atrial fibrillation is one of the most common persistent arrhythmias, affecting approximately 50 million people worldwide. The associated risk of stroke is five times higher in this population than in those without the condition. Therefore, anticoagulation therapy to prevent cardioembolic stroke has become a key focus in the treatment of atrial fibrillation. Clinical guidelines prioritize the use of DOACs for treating such patients. However, bleeding, particularly gastrointestinal bleeding, remains a major complication of DOACs treatment. This side effect leads to undertreatment in many patients. Thus, there is an urgent need to develop safer anticoagulants.

Anticoagulants, sometimes referred to as blood thinners, interrupt the process of normal blood clotting (coagulation). The coagulation cascade is highly complex, involving numerous cellular proteins working together to achieve hemostasis. For patients with atrial fibrillation, there are multiple types of anticoagulants available. These different anticoagulants inhibit various points of the coagulation cascade, preventing the formation of blood clots.

Among them, coagulation factor XI has been regarded as a potential target for safer anticoagulants. Studies have shown that coagulation factor XI is crucial in thrombosis but is not essential for normal hemostasis in most cases. In populations with hereditary coagulation factor XI deficiency, the incidence of thrombotic events is significantly reduced, while the risk of spontaneous bleeding does not increase notably. Therefore, coagulation factor XI inhibitors are expected to separate thrombosis from hemostatic function, providing a safer option for anticoagulant therapy.

In January 2025, Anthos Therapeutics announced that the positive results of Abelacimab in the Phase 2 clinical trial AZALEA-TIMI 71 were published in The New England Journal of Medicine.

AZALEA-TIMI 71 is a randomized, active-controlled, blinded-endpoint, parallel-group Phase 2 clinical study with a total of 1,287 patients enrolled. The primary endpoint is to evaluate the effects of two blinded doses of abelacimab compared to standard therapy with the oral anticoagulant rivaroxaban in atrial fibrillation patients with moderate to high stroke risk. The primary endpoint is a composite of major bleeding or clinically relevant non-major bleeding events. The secondary endpoint is major bleeding alone. Patients were randomized in a 1:1:1 ratio and administered either 90 mg or 150 mg of abelacimab subcutaneously once a month, or the active control drug at 20 mg once daily.

Study shows that in patients with atrial fibrillation, Abelacimab significantly reduced bleeding events across all primary and secondary endpoints compared to standard treatment with direct oral anticoagulants (DOAC). A once-monthly subcutaneous injection of 150 mg of Abelacimab can reduce factor XI levels by up to 99%, with effects lasting over two years.

In addition, in a phase 2 clinical trial targeting patients after knee surgery, the incidence of venous thromboembolism within 10 days after a single intravenous injection of abelacimab was reduced by 80% compared with enoxaparin.

Anthos Therapeutics once stated that, based on the extensive positive data from the aforementioned studies, the safety of Abelacimab in surgical patients and those undergoing antiplatelet therapy further validates the principle of inhibiting coagulation factor XI, which has the potential to prevent thrombotic events without affecting normal hemostasis.

Notably, even in situations with the highest bleeding risk, such as surgery, invasive procedures, or the use of antiplatelet therapy, the bleeding rate remained extremely low in patients treated with Abelacimab. This is attributed to its near-complete inhibition of factor XI. In other words, with an increasing amount of safety data available, if approved, Abelacimab would become the ideal choice for patients seeking a safer and more convenient anticoagulation therapy.

Anthos Therapeutics has initiated a Phase 3 trial for Abelacimab, enrolling high-risk atrial fibrillation patients deemed unsuitable for oral anticoagulation therapy, with data potentially being released in 2026.

According to statistics and forecasts by QYR (Hengzhou Bozhi), the global anticoagulant drug market sales reached 32.19 billion USD in 2024 and are expected to reach 44.49 billion USD by 2031, with a compound annual growth rate (CAGR) of 4.8% (2025-2031).

Regeneron Pharmaceuticals is also developing therapeutic products targeting coagulation factor XI. In December 2024, Regeneron announced positive results from two Phase II clinical trials, ROXI-VTE-I and ROXI-VTE-II, in patients with venous thromboembolism (VTE) for its two new drugs targeting different domains of coagulation factor XI (FXI), designed to control thrombosis: REGN7508 (targeting the catalytic domain, aiming to maximize anticoagulant activity while minimizing bleeding risk) and REGN9933 (targeting the A2 domain, aiming to provide more options for high bleeding-risk patients unsuitable for existing anticoagulant therapies). The VTE rate for REGN7508 was superior to enoxaparin and non-inferior to apixaban, while REGN9933 was non-inferior to enoxaparin. All VTE events were asymptomatic, except for one patient in the apixaban cohort who experienced symptomatic pulmonary embolism.

That is, both of Regeneron's innovative monoclonal antibodies demonstrated significant antithrombotic effects in Phase 2 clinical trials, and no clinically significant bleeding events related to treatment were observed in any of the treatment groups. Based on these positive results, Regeneron is planning to advance both antibodies into Phase 3 clinical trials.

Meanwhile, the oral Factor XIa inhibitor Milvexian, co-developed by Bristol-Myers Squibb and Johnson & Johnson, is currently in Phase 3 clinical trials, being evaluated for its role in patients with atrial fibrillation, acute coronary syndrome, and stroke.

In addition, Bayer's Factor XIa inhibitor asundexian is currently being evaluated in a Phase 3 trial for its effectiveness in stroke patients.

Back to Novartis.

In recent years, Novartis has carried out drastic reforms in its product pipeline, spinning off its generics division Sandoz and integrating its pharmaceuticals and oncology divisions. Currently, Novartis' product pipeline includes cardiovascular (including nephrology), oncology, immunology, and neuroscience.

The cardiovascular pipeline is Novartis' core pipeline. In recent years, the patent for Entresto (sacubitril/valsartan), Novartis’ foremost cash cow, is nearing expiration, and domestic pharmaceutical companies such as Hengrui have targeted the same market with various generic drugs. To address this challenge, Novartis acquired Leqvio (inclisiran, PCSK9 siRNA), the first and only marketed siRNA drug for lowering blood lipids.

It can be seen that Novartis' cardiovascular drug indications have gradually shifted from the treatment of cardiovascular diseases to the prevention of cardiovascular disease risks, and this acquisition further solidifies its continuously reinforced pipeline layout.

Novartis has officially emphasized that cardiovascular disease is the leading cause of death globally, but there is still a gap in innovative therapies. If Abelacimab can break through and successfully reach the market, it may revolutionize traditional anticoagulant drugs, which are prone to causing bleeding, becoming another blockbuster product for Novartis after the lipid-lowering drug Leqvio.

References:

One Injection per Month, Effective for 2 Years! Monoclonal Antibody Therapy Once Again Published in The New England Journal of Medicine

Prevention of Atrial Fibrillation and Stroke: Anticoagulants