General Information

Idelvion is a long-acting albumin fusion protein linking recombinant coagulation factor IX with recombinant albumin.

Idelvion was specifically approved for use in children and adults with hemophilia B for routine prophylaxis to prevent or reduce the frequency of bleeding episodes; on-demand control and prevention of bleeding episodes; and the perioperative management of bleeding.

Idelvion is supplied as a powder for solution for intravenous use after reconstitution only.

•One IU of Idelvion per kg body weight is expected to increase the circulating activity of Factor IX as follows:

Adolescents and adults: 1.3 IU/dL per IU/kg

Pediatrics (<12 years): 1 IU/dL per IU/kg

Administer intravenously. Do not exceed infusion rate of 10 mL per minute.

Control and prevention of bleeding episodes and perioperative management: •Dosage and duration of treatment with Idelvion depends on the severity of the Factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition, age and recovery of Factor IX. •Determine the initial dose using the following formula: •Required Dose (IU) = Body Weight (kg) x Desired Factor IX rise (% of normal or IU/dL) x (reciprocal of recovery (IU/kg per IU/dL)) •Adjust dose based on the patient’s clinical condition and response.

Routine prophylaxis: •Patients ≥12 years of age: 25-40 IU/kg body weight every 7 days. Patients who are well-controlled on this regimen may be switched to a 14-day interval at 50-75 IU/kg body weight. •Patients <12 years of age: 40-55 IU/kg body weight every 7 days.

Clinical Results

FDA Approval

The FDA approval of Idelvion was based in part on the following trials:

A global safety and efficacy trial assessing rIX-FP for prophylaxis treatment once every 7, 10 and 14 days and on-demand treatment of bleeding episodes in 63 previously-treated patients (12-61 years of age) with hemophilia B (FIX activity < or = 2% of normal). In one arm, 23 previously on-demand patients received only on-demand treatment for 6 months and then switched to 7-day prophylaxis treatment. In the other arm, 40 patients received 7-day prophylaxis treatment for 6 months and then, if eligible, switched to a 10- or 14-day prophylaxis treatment interval for 12 to 18 months. In patients who started on-demand treatment then switched to prophylaxis treatment, annualized spontaneous bleeding rates (AsBR) decreased by 100 percent from a median 15.43 during the on-demand treatment phase to 0.00 in the prophylaxis treatment phase (p<0.0001). Among patients who started on 7-day prophylaxis treatment then switched to 10- or 14-day prophylaxis treatment, the median AsBR rate was 0.00. In total, 99 percent of bleeding events were successfully managed with one or two infusions, with 94 percent of bleeds controlled with only one infusion regardless of the cause or location. Patients on 14-day prophylaxis treatment used a median dose of 75 IU/kg, which was 50 percent less therapy compared with their previously used FIX products. None of the patients developed inhibitors to factor IX or antibodies to rIX-FP. Related adverse events were reported in five patients (7.9 percent). The most common adverse reaction in clinical trials was headache. Overall, rIX-FP was well tolerated.

A global study evaluated the safety and efficacy of rIX-FP for prophylaxis treatment once every 7 days and treatment of bleeding episodes in 27 children, age 1-11 years, with hemophilia B (FIX activity < or = 2% of normal). Patients were treated for 12 months and/or 50 exposure days. The median AsBR was 0.00, and similar for patients under age 6 and those between 6 and 11 years. In total, 97 percent of bleeding episodes were successfully managed by one or two infusions, with 89 percent treated with only one infusion. Overall, the pharmacokinetic profile demonstrated a greater than 5-fold longer half-life, reduced clearance for rIX-FP versus other FIX products, supporting prophylaxis treatment intervals every 7 to 14 days. Investigators rated 96 percent of the treatments as effective (excellent or good). A total of 25 patients achieved 50 or more exposure days. None of the patients developed inhibitors to factor IX or antibodies to rIX-FP, and there were no related adverse events or withdrawals from the study.

A surgical sub-group analysis included in the phase III studies as part of the global PROLONG-9FP clinical program. This abstract evaluated the use of rIX-FP to prevent bleeding during and post-surgery in 10 patients with hemophilia B (ages 8 to 51 years). The results showed that a single dose of rIX-FP was sufficient to maintain hemostasis during surgery.