Abelacimab

Novartis has announced that it will be expanding its late-stage cardiovascular pipeline by acquiring Anthos Therapeutics for approximately $3.1bn. The deal gives Novartis access to abelacimab, which is currently in phase 3 development for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). Approximately 1.5 million people in the UK are living with AF, the most common form of abnormal heart rhythm. The condition causes the heart to beat irregularly and often too fast, and is believed to contribute to one in five strokes. Anthos, launched by Blackstone Life Sciences and Novartis in 2019, has been advancing abelacimab through clinical development under a licence from Novartis. Abelacimab is a fully human monoclonal antibody that binds tightly to factor XI to block its activation and prevent the generation of its activated form, mimicking the natural factor XI deficiency associated with protection from thromboembolic disease. The candidate has already been shown in a phase 2 trial to significantly reduce bleeding events compared to standard-of-care direct-oral anticoagulant in AF patients and is now being evaluated in three late-stage studies for patients at risk of arterial and venous clots, one in AF patients and two in those with in cancer-associated thrombosis. Shreeram Aradhye, president, development and chief medical officer, Novartis, said: “We are excited to join forces to advance the development of abelacimab, a potential first-in-class treatment and safer approach for stroke prevention in AF as well as cancer-associated thrombosis. “Welcoming Anthos Therapeutics strengthens our focus in the cardiovascular space and complements our portfolio of… treatments, comprehensive clinical programmes, and strategic collaborations that help thousands of patients with heart disease around the world.” Under the terms of the agreement, which is expected to close in the first half of 2025, Anthos will receive an upfront payment of $925m and will be eligible for additional regulatory and sales milestones of up to $2.15bn. Anthos’ chief executive officer, Bill Meury, said: “Abelacimab has the potential to be an important treatment option for the millions of patients globally with AF at high risk of stroke, and we could not have more conviction in the potential of this asset. “With its deep roots in the cardiovascular space, Novartis is especially well positioned to advance abelacimab’s clinical development and bring this innovative product to healthcare providers and patients.”

The factor XI field has suffered setbacks since Novartis offloaded abelacimab. \n Novartis has brought abelacimab back into the fold. Six years after spinning the asset out to form Anthos Therapeutics, Novartis has struck a deal to buy Anthos for $925 million upfront to add the clot-busting prospect to its late-phase pipeline.Abelacimab, an anti-factor XI/XIa antibody, is designed to stop blood clot formation without raising the risk of bleeding and bruising. Current anticoagulants such as Bayer and Johnson & Johnson’s Xarelto act on both thrombosis and hemostasis, meaning the clot-prevention benefits are offset by an increased risk of bleeding.Anthos has gone some way to showing abelacimab has an edge over the incumbents, linking the drug candidate to an 80% reduction in venous thromboembolism compared to enoxaparin and a lower rate of bleeding events than Xarelto in phase 2 trials. The biotech started three phase 3 trials in 2022.Responsibility for wrapping up the phase 3 studies, which have completion dates in 2026, looks set to fall on Novartis. The drugmaker has agreed to pay $925 million upfront, plus up to $2.15 billion in regulatory and sales milestones, to buy Anthos and expects the deal to close in the first half of 2025. Blackstone Life Sciences committed $250 million to set up Anthos with Novartis in 2019. Buying Anthos will move Novartis back into competition with other developers of factor XI candidates. A clutch of drug developers are going after the target in the belief they can improve on non-vitamin K oral anticoagulants. That older drug class, which includes Xarelto and Bristol Myers Squibb and Pfizer’s Eliquis, dominates the space, but the top players are set to face generic competition in the coming years.The factor XI field has suffered setbacks since Novartis offloaded abelacimab. Bayer found about twice as many people died of a heart attack, stroke or other cardiovascular event when taking its factor XIa inhibitor asundexian than Eliquis. BMS and J&J’s milvexian failed a phase 2 trial, but the partners still moved the factor XIa inhibitor into a trio of phase 3 studies in 2023. However, the field remains competitive. Regeneron is developing two antibodies that hit different domains of factor XI, one designed to maximize anticoagulation and another that may be less effective but also less likely to cause bleeding. The Big Biotech reported phase 2 data on the candidates late last year.Novartis initially ducked out of the race in the belief its treatments for heart failure and plaque-clogged arteries were enough to occupy its cardiovascular team. However, CEO Vas Narasimhan, M.D., said Novartis was continuing to monitor the factor XI space on an earnings call in 2022, telling analysts that he had “a keen eye” on the size of studies and the amount of investment that will be required to differentiate on safety. Narasimhan’s focus reflected the knowledge that factor XI inhibitors will need to compete with relatively cheap generic copies of drugs such as Eliquis and Xarelto, although Anthos’ subsequent choice of phase 3 indications somewhat sidestepped the competition.The lead indication is prevention of stroke and systemic embolism in patients with atrial fibrillation. That trial is enrolling 1,900 people who are unsuitable for oral anticoagulants such as Eliquis and Xarelto and is comparing abelacimab to placebo. The other trials have active controls—Eliquis and a low molecular weight heparin—and are enrolling patients with cancer-associated blood clots in their veins.