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

The FDA has granted a fast track designation to abelacimab (MAA868) for the treatment of thrombosis associated with cancer, according to an announcement from Anthos Therapeutics.¹

Abelacimab, a novel, highly selective, fully humanized monoclonal antibody, is designed to induce effective hemostasis-sparing anticoagulation through factor XI inhibition.

“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 gastrointestinal/genitourinary cancers who are at an even higher risk of bleeding and can be further burdened by the inconvenience of daily injections,” Dan Bloomfield, MD, FACC, FAHA, chief medical officer at Anthos Therapeutics, stated in a press release. “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.”

Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, is the second-leading cause of death in patients with cancer, trailing only cancer itself. Currently, the only approved anticoagulants to treat venous thromboembolism carry an increased risk of bleeding.

A prior pharmacokinetic and pharmacodynamic study found that abelacimab elicited robust suppression of factor XI within an hour of administration, and near maximum inhibition was maintained for up to 30 days. Additionally, a single dose of abelacimab reduced the rate of venous thromboembolism by 80% vs enoxaparin sodium at 10 days in patients who received knee surgery, according to findings from a phase 2 study (EudraCT: 2019-003756-37).²

Abelacimab is currently undergoing further investigation in the phase 2 AZALEA-TIMI 71 trial (NCT04755283), plus the complementary phase 3 ASTER (NCT05171049) and MAGNOLIA (NCT05171075) trials.

Although the AZALEA-TIMI 71 trial is not restrictive to patients with cancer, it is evaluating abelacimab vs open-label rivaroxaban to measure the rate of major or clinically relevant non-major (CRNM) bleeding events in patients at least 55 years of age with atrial fibrillation who are at a moderate or high risk of stroke.³

The trial completed enrollment in December 2021 with 1287 patients at 95 global sites in the United States, Canada, Europe, and Asia. In the 2 experimental treatment groups, patients received subcutaneous middle- or high-dose abelacimab monthly compared with the control group, which was given 20 mg of oral rivaroxaban once per day.

The currently recruiting, multicenter, open-label, blinded end point ASTER trial is enrolling patients with cancer-associated venous thromboembolism.⁴ Eligible patients must be at least 18 years of age with a confirmed cancer diagnosis other than basal cell carcinoma or squamous cell carcinoma of the skin. Patients are eligible within 72 hours from a qualifying venous thromboembolism if anticoagulation therapy with a therapeutic dose of direct anticoagulants for at least 6 months is indicated.

Enrolled patients in ASTER will be randomized to receive a 150-mg dose of intravenous abelacimab, followed by monthly subcutaneous administration of the same dose, or 10 mg of apixaban twice daily for the first 7 days, then 5 mg of apixaban twice daily for up to 6 months.

The MAGNOLIA trial will specifically enroll patients with unresectable, locally advanced, metastatic, or nonmetastatic gastrointestinal or genitourinary cancer who will not undergo intended curative surgery during the study.⁵ Patients will be eligible within 72 hours from diagnosis of a qualifying venous thromboembolism if anticoagulation therapy for at least 6 months is indicated. Patients need to have confirmed symptomatic or incidental proximal lower limb acute deep vein thrombosis, and/or a confirmed symptomatic pulmonary embolism, an incidental pulmonary embolism in a segmental, or larger pulmonary artery.

Enrolled patients in MAGNOLIA will be randomized to receive a 150-mg dose of intravenous abelacimab, followed by monthly subcutaneous administration of the same dose, or subcutaneous dalteparin given daily at 200 IU/kg for the first month and 150 IU/kg for up to 6 months.

The primary end point of the ASTER and MAGNOLIA trials is time to first event of centrally adjudicated venous thromboembolism recurrence, consisting of a new proximal deep venous thrombosis, new or fatal pulmonary embolism, including unexplained death for which pulmonary embolism cannot be ruled out. Secondary end points include time to the first event of International Society on Thrombosis and Hemostasis–adjudicated major or CRNM bleeding events, and the net clinical benefit defined as survival without venous thrombosis recurrence, or major or CRNM bleeding events.

“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,” Jean Marie Connors, MD, an associate professor of hematology at Harvard Medical School, stated 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.”

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://prn.to/3yVZZos
2. Verhamme P, Yi BA, Segers A, et al. Abelacimab for prevention of venous thromboembolism. N Engl J Med. 2021;385(7):609-617. doi:10.1056/NEJMoa2105872
3. Safety and tolerability of abelacimab (MAA868) vs. rivaroxaban in patients with atrial fibrillation (AZALEA-TIMI 71). ClinicalTrials.gov. Updated May 20, 2022. Accessed July 11, 2022. https://clinicaltrials.gov/ct2/show/NCT04755283?term=Abelacimab&draw=2&rank=1
4. A study comparing abelacimab to apixaban in the treatment of cancer-associated VTE (ASTER). ClinicalTrials.gov. Updated June 8, 2022. Accessed July 11, 2022. https://clinicaltrials.gov/ct2/show/NCT05171049
5. A study comparing abelacimab to dalteparin in the treatment of gastrointestinal/genitourinary cancer and associated VTE (MAGNOLIA). ClinicalTrials.gov. Updated March 31, 2022. Accessed July 11, 2022. https://clinicaltrials.gov/ct2/show/NCT05171075