FDA Grants Fast Track Designation to Abelacimab for Cancer-Associated Thrombosis

The FDA has granted fast track designation to abelacimab (formerly MAA 868), a dual-acting fully human monoclonal antibody that selectively targets Factor XI and Factor XIa with high affinity, for the treatment of thrombosis associated with cancer, according to an announcement by Anthos Therapeutics.¹

In patients with cancer, venous thromboembolism (VTE), including both deep vein thrombosis and pulmonary embolism is the second most common cause of death. The anticoagulants that are currently available for the treatment of VTE can increase the risk of bleeding in these patients, underscoring an unmet medical need.

Fast track designations are designed to address unmet medical needs by facilitating the development and expediting the review of treatments for serious medical conditions, like thrombosis. Agents that are granted fact track status may be eligible for more frequent interactions with the FDA to discuss the development process. Moreover, if the program criteria are met, an application submitted for the agent may be eligible for a potential rolling review, accelerated approval, and priority review.

"Caring for cancer patients is a delicate and complex process, requiring a fine balance between the risks and benefits of their anticoagulant treatments. Managing thrombosis episodes is of the utmost importance for physicians, patients, and their caregivers, as untreated blood clots or bleeding episodes associated with currently available anticoagulants, can have dire consequences," said Jean Marie Connors, MD, associate professor of Hematology at Harvard Medical School, in a press release. "The hemostasis sparing potential of FXI inhibitors, such as abelacimab, may represent an important treatment advance in how we manage patients moving forward."

Currently, abelacimab is being investigated in a phase 3 program in cancer-associated thrombosis. The program includes 2 studies with a combined target enrollment of approximately 2700 patients. The studies will be conducted at 220 treatment sites across 20 countries. It is the largest research program of any anticoagulant used for the treatment of cancer-associated thrombosis, according to Anthos Therapeutics.

In ASTER, an international multicenter, randomized, open-label, blinded endpoint evaluation, phase 3 study, treatment with abelacimab will be compared with apixaban for recurrence and bleeding in patients with cancer-associated VTE (NCT05171049). Approximately 1655 patients will be given abelacimab 150 mg via intravenous (IV) infusion on day 1 and subcutaneous (SC) monthly doses thereafter for up to 6 months in the experimental arm. Apixaban 10 mg will be administered orally, twice daily for the first 7 days, followed by 5 mg bid up to 6 months in the control arm.^1,2

The primary end point of the ASTER study is the time to the first event of centrally adjudicated VTE recurrence consisting of new proximal deep venous thrombosis, new pulmonary embolism (PE), or fatal PE, including unexplained death. The secondary end point of the study include time to the first event of International Society on Thrombosis and Haemostasis-adjudicated major or clinically relevant non-major bleeding events, and the net clinical benefit of abelacimab vs apixaban.

The second study exploring as thrombosis treatment in patients with cancer is MAGNOLIA (NCT05171075). MAGNOLIA is an international multicenter, randomized, open-label, blinded endpoint evaluation, phase 3 study. In the study, treatment with abelacimab will be compared with dalteparin in roughly 1020 patients with GI and GU cancers and associated VTE abelacimab will be dosed at 150 mg and administered IV on Day 1 SC monthly thereafter for up to 6 months. In the control arm, patients will be administered dalteparin SC daily at 200 IU/kg/day for the first month, and then 150 IU/kg/day up to 6 months.^1,3

MAGNOLIA will explore the same primary and secondary end points as ASTER. Both studies of abelacimab are actively recruiting patients with cancer-associated VTE.^1-3

"We believe that abelacimab has the potential to provide patients with cancer-associated thrombosis an enhanced safety profile and overall low risk of bleeding, without sacrificing any efficacy of currently available agents. This unmet need is particularly true in patients with GI/GU cancers who are at an even higher risk of bleeding and can be further burdened by the inconvenience of daily injections," said Dan Bloomfield, chief medical officer of Anthos Therapeutics, in a statement. "Fast track designation by the FDA is a significant milestone for abelacimab and Anthos Therapeutics, but more importantly represents another hopeful step forward for patients. We look forward to working closely with the FDA on our clinical trial program to bring once-monthly abelacimab to patients in need."

_REFERENCES:

_{1. Anthos Therapeutics announces that abelacimab has Received FDA fast track designation for the treatment of thrombosis associated with cancer. News release. Anthos Therapeutics. July 11, 2022. Accessed July 11, 2022. https://bit.ly/3IsGO8S}

_{2. A study comparing abelacimab to apixaban in the treatment of cancer-associated VTE (ASTER). Clinicaltrial.gov. Updated June 9, 2022. Accessed July 11, 2022.}

_{3. A study comparing abelacimab to dalteparin in the treatment of gastrointestinal/genitourinary cancer and associated VTE (MAGNOLIA). Updated March 31, 2022. Accessed July 11, 2022.}