ted with enoxaparin for a median of 9 days. Patients in both treatment groups were followed for safety, including bleeding events, for up to 77 days.
Patients randomized to the BEVYXXA arm received BEVYXXA 160 mg orally on Day 1, then 80 mg once daily for 35 to 42 days AND enoxaparin subcutaneous placebo once daily for 6 to 14 days. Patients randomized to the enoxaparin arm received enoxaparin 40 mg subcutaneously once daily for 6 to 14 days AND BEVYXXA placebo orally once daily for 35 to 42 days.
Patients with severe renal impairment (creatinine clearance ≥ 15 and < 30 mL/min) received reduced doses of study medications (BEVYXXA 80 mg loading dose, then 40 mg once daily or enoxaparin 20 mg once daily) along with corresponding placebo.
Patients taking a concomitant P-gp inhibitor received BEVYXXA 80 mg loading dose, then 40 mg once daily or enoxaparin 40 mg subcutaneously once daily for 6 to 14 days along with corresponding placebo.
Hemorrhage
The most common adverse reactions with BEVYXXA were related to bleeding (> 5%) with major bleeding occurring in less than 1% of patients (see TABLE 1).
Overall, 54% of patients receiving BEVYXXA experienced at least one adverse reaction vs. 52% with enoxaparin. The frequency of patients reporting serious adverse reactions was similar between BEVYXXA (18%) and enoxaparin (17%). In the APEX trial, the most frequent reason for treatment discontinuation was bleeding, with an incidence rate of 2.4% for BEVYXXA vs. 1.2% for enoxaparin.
The primary and secondary safety outcomes in APEX were bleeding-related events.
A summary of major and clinically relevant non-major (CRNM) bleeding events in the overall safety population is shown in Table 1. Most CRNM events (86%) were mild to moderate in severity, and the majority (62%) did not require medical intervention.
The incidence of fatal bleeding was the same in the BEVYXXA and enoxaparin treatment groups (1 in each group).
Table 1: Bleeding Events in APEX through 7 Days after Discontinuation of All Study Drugs (Safety Population)
Parameter BEVYXXA
(N=3,716) Enoxaparin
(N=3,716) BEVYXXA vs. Enoxaparin RR
(95% CI)
* Major bleeding event was defined as clinically overt bleeding that met one of the following criteria: a reduction in hemoglobin of a least 2 g/dL within 48 hours of an overt bleeding event; a transfusion of at least two units of whole blood or packed red blood cells; a critical area; e.g., intraocular, intracranial, intraspinal, intramuscular with compartment syndrome, retroperitoneal, intra-articular, pericardial, or a fatal outcome. Retinal hemorrhages secondary to diabetic retinopathy or conjunctival bleeds did not qualify as major bleeds. † CRNM bleeding was defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact (visit or telephone call) with a physician, (temporary/permanent) cessation of the study treatment, or associated with discomfort for the patient such as pain or impairment of activities of daily life.
Major Bleeding * 25 (0.67) 21 (0.57) 1.19 (0.67, 2.12)
p = 0.554
Gastrointestinal (GI) 19 (0.51) 9 (0.24)
Intracranial Hemorrhage 2 (0.05) 7 (0.19)
Intraocular 0 (0) 1 (0.03)
Fatal Bleeding 1 (0.03) 1 (0.03)
Clinically Relevant Non-Major Bleeding † 91 (2.45) 38 (1.02) 2.39 ( |
