On February 11, 2025, Novartis announced the acquisition of Anthos Therapeutics, a private clinical stage biopharmaceutical company headquartered in Boston. Anthos has a late stage drug Abelacimab under development for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

Novartis will make a prepayment of $925 million upon completion of the transaction, subject to certain customary adjustments, and may pay an additional $2.15 billion upon reaching regulatory and sales milestones, totaling $3.1 billion. The transaction is expected to be completed in the first half of 2025, subject to meeting customary closing conditions.

According to Novartis' official announcement, this transaction fully aligns with Novartis' growth strategy and treatment focus, and leverages the company's strength and expertise in the cardiovascular field.

01. Core monoclonal antibody: one dose per month, effective for 2 years
Anthos was founded in 2019 as a joint venture between Blackstone Life Sciences and Novartis. It is a clinical stage biopharmaceutical company specializing in the treatment of cardiovascular diseases. It is worth mentioning that Anthos has exclusive global rights authorized by Novartis to develop, manufacture, and commercialize its core product Abelacimab.

Abelacimab is a novel and highly selective all human monoclonal antibody that can tightly bind to coagulation factor XI, prevent its activation, and simultaneously inhibit coagulation factor XI and its activated form, coagulation factor XIa, to prevent thrombosis. This drug provides protective effects by simulating the state of natural coagulation factor XI deficiency, while avoiding the common bleeding risks of traditional anticoagulant drugs.

A proof of concept study published in the New England Journal of Medicine in 2021 showed that Abelacimab reduced venous thromboembolism (VTE) in patients by approximately 80% compared to standard control drugs. In July 2022, Abelacimab was granted fast track status by the FDA for the treatment of cancer-related thrombosis. In September of the same year, the drug once again obtained fast track qualification 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, and its associated stroke risk is five times higher than that of the population without this disease. Therefore, anticoagulant therapy for preventing cardioembolic stroke has become a key focus of atrial fibrillation treatment. Clinical guidelines prioritize the use of DOAC for the treatment of such patients. However, bleeding, especially gastrointestinal bleeding, remains the main complication of DOACs treatment. This side effect leads to inadequate treatment for many patients. Therefore, there is an urgent need to develop safer anticoagulants.

Anticoagulants are sometimes referred to as blood thinners, which can interrupt the normal process of blood clotting (coagulation). The coagulation cascade system is very complex, with many cellular proteins involved in playing a hemostatic role together. There are more than one anticoagulant used for atrial fibrillation patients, and different anticoagulants inhibit different parts of the coagulation cascade system, preventing blood clots from forming.

Among them, coagulation factor XI has been considered a potential target for safer anticoagulants. Research has shown that coagulation factor XI is crucial in thrombus formation, but in most cases it is not necessary for normal hemostasis. In populations with hereditary coagulation factor XI deficiency, the incidence of thrombotic events is significantly reduced, while the risk of spontaneous bleeding is not significantly increased. Therefore, inhibitors of coagulation factor XI are expected to achieve the separation of thrombus formation and hemostatic function, providing a safer option for anticoagulant therapy.

In January 2025, Anthos announced that the positive results of Abelacimab's 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 1287 patients enrolled. The primary endpoint is to evaluate the efficacy of two blinded doses of abelacimab compared to the standard therapy of oral anticoagulant rivaroxaban in atrial fibrillation patients with moderate to high risk of stroke. The primary endpoint of the study is the composite endpoint of the incidence of major bleeding or clinically relevant non major bleeding events. The secondary endpoint is severe bleeding itself. Patients were randomly divided into 1:1:1 groups and subcutaneously administered 90 mg, 150 mg abelacimab once a month, or 20 mg of active control drug once a day.

Research has shown that in patients with atrial fibrillation, Abelacimab significantly reduces bleeding events at all primary and secondary endpoints compared to standard treatment with direct oral anticoagulants (DOAC). Subcutaneous injection of 150mg Abelacimab once a month can reduce coagulation factor XI levels by 99%, and the effect can last for more than 2 years.

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

Anthos officials once stated that based on a large amount of positive data from the aforementioned research, the safety of Abelacimab in surgical patients and patients receiving antiplatelet therapy further validates the principle of inhibiting coagulation factor XI, which may prevent thrombotic events without affecting normal hemostasis.

It is worth mentioning that even in situations with the highest risk of bleeding, such as surgery, invasive procedures, or antiplatelet therapy, patients receiving Abelacimab treatment still have extremely low bleeding rates, attributed to its almost complete inhibition of factor XI. That is to say, currently, the safety data of Abelacimab is increasing, and if approved, it will become an ideal choice for patients seeking safer and more convenient anticoagulant therapy.

Anthos has started a phase 3 trial of Abelacimab, with high-risk atrial fibrillation patients considered unsuitable for oral anticoagulant therapy included. Data may be released in 2026.

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

Regeneron Pharmaceuticals is also developing targeted therapy products for coagulation factor XI. In December 2024, Regeneron announced the development of two new drugs, REGN7508 (targeting the catalytic domain to maximize anticoagulant activity and minimize bleeding risk) and REGN9933 (targeting the A2 domain to provide more options for high-risk bleeding patients who are not suitable for existing anticoagulant therapies), aimed at controlling thrombosis in patients with venous thromboembolism (VTE). The results of two phase II clinical studies, ROXI-VTE-I and ROXI-VTE-II, were positive: REGN7508 had a superior VTE rate to enoxaparin and was not inferior to apixaban, while REGN9933 was not inferior to enoxaparin. All VTE events were asymptomatic, except for one patient in the apixaban cohort who had symptomatic pulmonary embolism.

That is, both innovative monoclonal antibodies of Regeneron showed significant antithrombotic effects in phase 2 clinical trials, and no clinically significant bleeding events related to treatment were observed in all treatment groups. Based on this positive result, Regenerative Element is planning to push these two antibodies towards Phase 3 clinical trials.

At the same time, Milvexian, an oral coagulation factor XIa inhibitor jointly developed by Bristol Myers Squibb and Johnson&Johnson, is currently undergoing phase 3 clinical trials to evaluate its efficacy in patients with atrial fibrillation, acute coronary syndrome, and stroke.

In addition, Bayer's coagulation factor XIa inhibitor asundxian is currently being evaluated for its efficacy in stroke patients in phase 3 trials.

In recent years, Novartis has undergone significant reforms to its product pipeline, divesting its generic drug division, Sandoz, and integrating its pharmaceutical and oncology divisions. Currently, Novartis' product pipeline includes cardiovascular (including kidney disease), oncology, immunology, and neuroscience.

The cardiovascular pipeline is the core pipeline of Novartis. In recent years, Novartis has been hit hard by the expiration of the patent for Entresto (sacubitril valsartan sodium), and various generic drugs from domestic pharmaceutical companies such as Hengrui are targeting the same market. The siRNA drug Leqvio (inclisiran, PCSK9 siRNA) purchased to address this dilemma is 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 is a further consolidation of its continued pipeline layout.

Novartis officials have emphasized that cardiovascular disease is the leading cause of death worldwide, but there is still a gap in innovative therapies. If Abelacimab can break through the encirclement and be successfully launched, it may overturn the disadvantage of traditional anticoagulant drugs that are prone to bleeding and become another heavyweight product of Novartis after the lipid-lowering drug Leqvio.

Source: https://pharm.jgvogel.cn/c1487217.shtml