IDELVION ® , Coagulation Factor IX (Recombinant), Albumin Fusion Protein (rIX-FP), a recombinant DNA-derived coagulation Factor IX concentrate, is indicated in children and adults with Hemophilia B (congenital Factor IX deficiency) for: On-demand treatment and control of bleeding episodes Perioperative management of bleeding Routine prophylaxis to reduce the frequency of bleeding episodes Limitations of Use: IDELV...
For intravenous use after reconstitution only. Each single-dose vial of IDELVION contains the recombinant Factor IX potency in international units (IU) that is stated on the carton and vial label. Dosage and duration of treatment with IDELVION depends on the severity of Factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition, age and recovery of Factor IX. The calculation of...
IDELVION is supplied as a lyophilized powder in single-dose vials containing the labeled amount of Factor IX activity, expressed in international units (IU). IDELVION is packaged with 2.5 mL (for reconstitution of 250, 500 or 1000 IU vials) or 5 mL (for reconstitution of 2000 or 3500 IU vials) of Sterile Water for Injection, USP, one Mix2Vial filter transfer set, and one sterile alcohol swab. Components are not ma...
www.fda.gov/medwatch
www.IDELVION.comIDELVION®, Coagulation Factor IX (Recombinant), Albumin Fusion Protein (rIX-FP), a recombinant DNA-derived coagulation Factor IX concentrate, is indicated in children and adults with Hemophilia B (congenital Factor IX deficiency) for:
Limitations of Use:
IDELVION is not indicated for immune tolerance induction in patients with Hemophilia B.
For intravenous use after reconstitution only.
| Required Units (IU) = Body Weight (kg) × Desired Factor IX rise (% of normal or IU/dL) × (reciprocal of recovery (IU/kg per IU/dL)) |
| OR |
| Increase in Factor IX IU/dL (or % of normal) = Dose (IU) × Recovery (IU/dL per IU/kg)/body weight (kg) |
On-demand Treatment and Control of Bleeding Episodes
A guide for dosing IDELVION for the on-demand treatment and control of bleeding episodes is provided in Table 1. Dosing should aim at maintaining a plasma Factor IX activity level at or above the plasma levels (in % of normal or IU/dL) outlined in Table 1.
| Type of Bleeding Episode | Circulating Factor IX Activity Required [% or (IU/dL)] | Frequency of Dosing (hours) | Duration of Therapy (days)* |
|---|---|---|---|
| Minor or Moderate Uncomplicated hemarthrosis, muscle bleeding (except iliopsoas) or oral bleeding | 30-60 | 48-72 | At least 1 day, until bleeding stops and healing is achieved. Single dose should be sufficient for majority of bleeds. |
| Major Life or limb threatening hemorrhage, deep muscle bleeding, including iliopsoas, intracranial, retropharyngeal | 60-100 | 48-72 | 7-14 days, until bleeding stops and healing is achieved. Maintenance dose weekly. |
* Adapted from the WFH Guidelines for the Management of Hemophilia.
Perioperative Management of Bleeding
A guide for dosing IDELVION for perioperative management of bleeding is provided in Table 2.
| Type of Surgery | Circulating Factor IX Activity Required [% or (IU/dL)] | Frequency of Dosing (hours) | Duration of Therapy (days)* |
|---|---|---|---|
| Minor (including uncomplicated tooth extraction) | 50-80 | 48-72 | At least 1 day, or until healing is achieved. Single dose should be sufficient for a majority of minor surgeries. |
| Major (including intracranial, pharyngeal, retropharyngeal, retroperitoneal) | 60-100 (initial level) | 48-72 | 7-14 days, or until bleeding stops and healing is achieved. Repeat dose every 48-72 hours for the first week or until healing is achieved. Maintenance dose 1-2 times per week. |
* Adapted from the WFH Guidelines for the Management of Hemophilia.
Routine Prophylaxis
For patients ≥12 years of age, the recommended dose is 25-40 IU IDELVION per kg body weight every 7 days. Patients who are well-controlled on a 7-day regimen may be switched to a 14-day interval at 50-75 IU IDELVION per kg body weight [see Clinical Studies (14)].
For patients <12 years of age, the recommended dose is 40-55 IU IDELVION per kg body weight every 7 days.
The procedures below are provided as general guidelines for the preparation and reconstitution of IDELVION.
IDELVION Reconstitution Instructions
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For intravenous injection only.
IDELVION is a pale yellow to white lyophilized powder supplied in single-dose vials containing nominally 250, 500, 1000, 2000, or 3500 IU of Factor IX potency. The actual factor IX potency is labeled on each vial and carton.
IDELVION is contraindicated in patients who have had life-threatening hypersensitivity reactions to IDELVION, or its components, including hamster proteins [see Warnings and Precautions (5.1)].
Hypersensitivity reactions have occurred. Early signs of hypersensitivity reactions, which can progress to anaphylaxis include angioedema, chest tightness, hypotension, generalized urticaria, wheezing, and dyspnea. If symptoms of hypersensitivity or anaphylaxis occur, immediately discontinue administration and initiate appropriate treatment.
IDELVION contains trace amounts of Chinese hamster ovary (CHO) proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.
The formation of neutralizing antibodies (inhibitors) to Factor IX has been reported with IDELVION [see Adverse Reactions (6.3)]. Monitor all patients treated with IDELVION for the development of neutralizing antibodies (inhibitors) by appropriate clinical observations or laboratory tests. Perform an assay that measures Factor IX inhibitor concentration if expected plasma Factor IX activity levels are not attained, or if the bleeding is not controlled with an appropriate dose.
Patients with Factor IX inhibitors are at an increased risk of severe hypersensitivity reactions or anaphylaxis if re-exposed to Factor IX. Evaluate patients experiencing allergic reactions for the presence of an inhibitor and closely monitor patients with inhibitors for signs and symptoms of acute hypersensitivity reactions, particularly during early phases of exposure to the product [see Warnings and Precautions (5.1)].
Thromboembolism (e.g., pulmonary embolism, venous thrombosis, and arterial thrombosis) may occur when using Factor IX-containing products. Because of the potential risk for thromboembolism with the use of Factor IX products, monitor for early signs of thromboembolism and consumptive coagulopathy when administering IDELVION to patients with liver disease, fibrinolysis, perioperative status, or risk factors for thromboembolic events or disseminated intravascular coagulation.
Nephrotic syndrome has been reported following attempted immune tolerance induction in hemophilia B patients with Factor IX inhibitors and a history of allergic reactions. The safety and efficacy of using IDELVION for immune tolerance induction have not been established.
The most common adverse reactions (incidence ≥1%) reported in clinical trials were headache, dizziness, hypersensitivity and rash.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice.
In five multicenter, prospective, open-label clinical trials with IDELVION, 114 previously treated patients (PTPs; exposed to a Factor IX-containing product for ≥100 exposure days (EDs)) received at least one infusion of IDELVION as part of on-demand treatment of bleeding episodes, perioperative management of major and minor surgical, dental, or other invasive procedures, routine prophylaxis, or pharmacokinetic evaluation. Twenty-seven children were <12 years of age, 9 adolescents were 12 to <18 years of age, and 78 adults were ≥18 to ≤65 years of age. A total of 16,326 injections were administered over a median of 1,543.5 days (range: 25 to 2,565 days).
Adverse reactions that occurred in >0.5% of subjects are listed in Table 3.
| MedDRA Standard System Organ Class | Adverse Reaction | Number of subjects n (%), (N=114) |
|---|---|---|
| Nervous system disorders | Headache | 2 (1.8) |
| Dizziness | 2 (1.8) | |
| Immune system disorders | Hypersensitivity | 1 (0.9) |
| Skin and subcutaneous tissue disorders | Rash | 1 (0.9) |
| Eczema | 1 (0.9) |
Safety of IDELVION was also evaluated in a completed study with 12 previously untreated patients (PUPs). The median number of EDs was 50 (range: 22 to 146) per subject, a total of 8 subjects achieved at least 50 EDs, of whom 3 subjects achieved ≥100 EDs.
Adverse drug reactions were reported in 2 of 12 subjects treated with IDELVION. One subject (8.3%) in the PUP study developed a high titer of factor IX inhibitors (peak titer 188 BU/mL) and the same subject (8.3%) developed hypersensitivity. One additional subject (8.3%) in the PUP study developed rash.
All subjects were monitored for inhibitory and binding antibodies to rIX-FP (specifically rFIX, pdFIX and albumin), and binding antibodies to CHO host cell proteins at the following time points: at screening, at 2-4 weeks, 12 weeks following the first infusion of IDELVION, every 3 months thereafter (every 6 months for binding antibodies in children). No subjects developed non-neutralizing antibodies against factor IX, or antibodies to albumin and CHO protein at any of the time points following infusion of IDELVION. One case of inhibitor development to Factor IX was reported in the clinical study which evaluated previously untreated patients. No antibodies to Factor IX have been observed in IDELVION clinical trials which enrolled previously treated patients.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, it may be misleading to compare the incidence of antibodies to IDELVION in the studies described above with the incidence of antibodies in other studies or to other products.
The following adverse reaction has been identified during post-approval use of IDELVION. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders: Factor IX inhibitor development
Risk Summary
There are no data with IDELVION use in pregnant women to inform on drug-associated risk. Animal reproduction studies have not been conducted using IDELVION. It is not known whether IDELVION can cause fetal harm or affect reproduction capacity when administered to a pregnant woman. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Risk Summary
There is no information regarding the excretion of IDELVION in human milk, the effect on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for IDELVION and any potential adverse effects on the breastfed infant from IDELVION or from the underlying maternal condition.
In clinical studies that included 34 previously treated patients (PTPs) <18 years old, the prophylactic administration with IDELVION every 7 days was successful in prevention of spontaneous bleeding episodes requiring treatment [see Clinical Studies (14)]. Of these, 7 subjects were ≥12 and <18 years old; 5 of these subjects switched to a 10- or 14-day prophylactic administration with IDELVION. There were no apparent differences in the safety profile in subjects <18 years as compared to adults [see Adverse Reactions (6.1)].
Compared to adults, incremental rIX-FP recovery appeared to be slightly lower and body weight-adjusted clearance appeared to be higher. Children may have higher Factor IX body weight-adjusted clearance, shorter half-life, and lower recovery. Higher dose per kilogram body weight or more frequent dosing may be needed in these patients [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].
Clinical studies of IDELVION did not include subjects over 65 years to determine whether or not they respond differently from younger subjects.
IDELVION, Coagulation Factor IX (Recombinant), Albumin Fusion Protein (rIX-FP) is a sterile, non-pyrogenic, lyophilized powder to be reconstituted with sterile Water for Injection (sWFI) for intravenous administration. IDELVION is available in single-dose vials containing nominally 250, 500, 1000, 2000, or 3500 IU of Factor IX formulated with sodium citrate, polysorbate 80, mannitol and sucrose. The actual amount of Factor IX activity in IU is labeled on each vial. After reconstitution of the lyophilized powder, all dosage strengths yield a clear, yellow to colorless solution. IDELVION contains no preservatives.
The active ingredient in IDELVION, recombinant human coagulation Factor IX albumin fusion protein, is a purified protein produced by recombinant DNA technology. It is generated by the genetic fusion of recombinant albumin to recombinant coagulation Factor IX. The genetic fusion of the cDNA of human albumin to the cDNA of human coagulation Factor IX enables the gene product to be expressed as a single recombinant protein designated as rIX-FP. The Factor IX portion of IDELVION is identical to the Thr148 allelic form of human plasma-derived Factor IX. The cleavable linker between the Factor IX and albumin moieties is derived from the endogenous activation peptide in native Factor IX. rIX-FP remains intact in the circulation until Factor IX is activated, whereupon albumin is cleaved from Factor IX, releasing activated Factor IX (FIXa) when it is needed for coagulation.
IDELVION is manufactured without the addition of proteins derived from human or animal source materials. IDELVION is a glycoprotein consisting of 1018 amino acids secreted by a genetically engineered Chinese hamster ovary (CHO) cell line. The CHO cell line secretes rIX-FP into a defined cell culture medium and the rIX-FP protein is purified by a process that does not require the use of a monoclonal antibody reagent. The manufacturing process incorporates three validated virus clearance steps, including virus inactivation by solvent/detergent treatment and virus removal by filtration.
The potency expressed in International Units is determined using an in vitro aPTT-based one-stage clotting assay against CSL Behring's manufacturing reference standard. This internal potency standard has been calibrated against the World Health Organization (WHO) International Standard for Factor IX concentrate by a one-stage clotting assay using synthetic silica and synthetic phospholipid-based reagents.
IDELVION is a recombinant protein that temporarily replaces the missing coagulation Factor IX needed for effective hemostasis. IDELVION is comprised of genetically fused recombinant coagulation Factor IX and recombinant albumin. Fusion with recombinant albumin extends the half-life of Factor IX [see Description (11) and Clinical Pharmacology (12.3)].
The administration of IDELVION increases plasma levels of Factor IX and can temporarily correct the coagulation defect in patients.
Adults ≥18 years
The pharmacokinetic (PK) profiles of IDELVION were evaluated following intravenous injections of single doses of 25, 50 or 75 IU/kg. The PK parameters were based on plasma Factor IX activity measured by the one-stage clotting assay. Blood samples for PK analysis were collected prior to dosing and up to 336 hours (14 days) after dosing.
Table 4 provides the pharmacokinetic parameters following a single 25 IU/kg, 50 IU/kg, or 75 IU/kg dose of IDELVION.
| PK Parameters | rIX-FP 25 (IU/kg) (N=7) | rIX-FP 50 (IU/kg) (N=47) | rIX-FP 75 (IU/kg) (N=8) |
|---|---|---|---|
| IR = incremental recovery recorded 30 minutes after injection; AUC = area under the Factor IX activity time curve; t1/2 = half-life; MRT = mean residence time; CL = body weight adjusted clearance; Vss = body weight adjusted volume of distribution at steady state. | |||
| IR (IU/dL)/(IU/kg) | 1.65 (11) | 1.30 (24) | 1.08 (20) |
| Cmax (IU/dL) | 41.1 (13) | 66.6 (27) | 82.0 (20) |
| AUC0-inf (h*IU/dL) | 4658 (36) | 7482 (28) | 9345 (20) |
| t1/2 (hours) | 118 (38) | 104 (25) | 104 (18) |
| MRT (hours) | 153 (24) | 143 (23) | 145 (14) |
| CL (mL/h/kg) | 0.57 (31) | 0.73 (27) | 0.84 (20) |
| Vss (dL/kg) | 0.86 (32) | 1.02 (28) | 1.20 (23) |
| Time to 1% Factor IX Activity (days)* | 22 (25) | 23 (19) | 25 (13) |
| Time to 3% Factor IX Activity (days)* | 14 (19) | 17 (19) | 18 (13) |
| Time to 5% Factor IX Activity (days)* | 10 (25) | 13 (20) | 15 (13) |
* = Estimated time to mean Factor IX activity maintained above the pre-specified percent (%)
IDELVION PK parameters following single or repeat dosing for up to 30 weeks were similar.
Subjects <18 years
Pharmacokinetic parameters of IDELVION were evaluated in 5 adolescents (12 to <18 years of age) and 27 children (0 to <12 years of age) in open-label, multi-center studies following a 50 IU/kg intravenous injection of IDELVION. The PK samples were collected prior to dosing and at multiple time points up to 336 hours (14 days) after dosing.
Table 5 summarizes the PK parameters calculated from the pediatric data of 32 subjects, 0 to <18 years of age. The parameters estimated were based on the plasma Factor IX activity over time profile. Compared to adults, incremental recovery is lower (15% to 27%) and body weight-adjusted clearance is higher (45% to 62%) in children.
| PK Parameters | 0 to <6 years (N=12) | 6 to <12 years (N=15) | 12 to <18 years (N=5) |
|---|---|---|---|
| IR = incremental recovery recorded 30 minutes after injection; AUC = area under the Factor IX activity time curve; t1/2 = half-life; MRT = mean residence time; CL = body weight adjusted clearance; Vss = body weight adjusted volume of distribution at steady-state. | |||
| IR (IU/dL)/(IU/kg) | 0.95 (22) | 1.06 (23) | 1.11 (28) |
| Cmax (IU/dL) | 48.3 (19) | 52.9 (23) | 55.3 (28) |
| AUC0-inf (h*IU/dL) | 4583 (33) | 5123 (31) | 5347 (48) |
| t1/2 (hours) | 90 (13) | 93 (21) | 87 (36) |
| MRT (hours) | 123 (14) | 129 (19) | 119 (31) |
| CL (mL/h/kg) | 1.18 (28) | 1.06 (29) | 1.08 (39) |
| Vss (dL/kg) | 1.42 (24) | 1.32 (20) | 1.16 (14) |
| Time to 1% Factor IX Activity (days) * | 17 (29) | 20 (22) | 19 (37) |
| Time to 3% Factor IX Activity (days) * | 12 (32) | 14 (22) | 13 (38) |
| Time to 5% Factor IX Activity (days) * | 9 (32) | 11 (26) | 11 (38) |
* = Estimated time to mean Factor IX activity maintained above the pre-specified percent (%)
Nonclinical studies evaluating the carcinogenic potential of IDELVION have not been conducted.
No macroscopic or microscopic pathologies in reproductive organs were observed in animals dosed every day for 28 days with 6.7 times the maximum recommended prophylactic clinical dose of 75 IU/kg IDELVION. No animal studies regarding impairment of fertility following IDELVION dosing were conducted.
The safety and efficacy of IDELVION were evaluated in a prospective, open-label, multicenter clinical study of 63 male previously treated patients (PTPs) with hemophilia B (≤2% endogenous Factor IX activity) who received at least one infusion of IDELVION as part of on-demand treatment and control of bleeding episodes, perioperative management of major and minor surgical, dental, or other invasive procedures, routine prophylaxis once every 7-, 10- or 14-day intervals, or pharmacokinetic evaluation. Subjects were aged 12 to 61 years; including 7 adolescent subjects aged 12 to 17. Subjects were treated for up to 27 months.
On-demand Treatment and Control of Bleeding Episodes
A total of 358 bleeding events were treated with IDELVION. Among them, 204 (57%) bleeding events were spontaneous, 140 (39%) events were traumatic and 14 (4%) events were unknown. In addition, a total of 267 (75%) episodes were joint bleeding events.
Overall treatment efficacy was assessed for each bleeding episode by the investigator based on a 4-point scale of excellent, good, moderate, or poor/no response. The efficacy of IDELVION for the on-demand treatment and control of bleeding episodes is summarized in Table 6.
| Number of Bleeding Episodes Requiring Treatment (n = 358) | |
|---|---|
| Number of injections to treat bleeding episodes | |
| 1 injection, n (%) | 335 (94) |
| 2 injections, n (%) | 18 (5) |
| >2 injections, n (%) | 5 (1.4) |
| Assessment of Efficacy* | |
| Excellent or Good, n (%) | 337 (94) |
| Moderate, n (%) | 9 (2.5) |
| Poor/no response, n (%) | 1 (0.3) |
* Excellent: Pain relief and/or unequivocal improvement in objective signs of bleeding and no additional infusion required in order to achieve hemostasis; Good: Definite pain relief and/or improvement in signs of bleeding at approximately 8 hours after the first infusion, but may require a second infusion; Moderate: Probable or slight beneficial effect, and requires more than two infusions to achieve hemostasis; Poor/no response: No improvement at all or condition worsens, additional hemostatic intervention is required. Responses evaluated at approximately 24 hours after treatment.
Perioperative Management of Bleeding
In the two effectiveness studies and the extension study, a total of 20 subjects (5-59 years of age) received IDELVION for perioperative management of 29 surgical procedures. Dose was individualized based on subject's PK and clinical response to treatment. These included orthopedic surgeries (n=14), a mastectomy with liposuction (n=1), a hemorrhoidectomy (n=2), rhinoplasty, submucosal resection and inferior turbinectomy (n=1), circumcision (n=3), tooth extractions (n=5), embolism of scrotal varicocele (n=1), excision of pigmented nevus (n=1) and endoscopic mucosal resection (n=1).
A single preoperative bolus was used in 97% (n=28) of surgeries. Hemostatic efficacy was rated as excellent or good for all surgeries at all time points for which hemostatic response was reported, except for one evaluation that was rated moderate at the 48-hour assessment. During the 14-day postoperative period, patients received between 0 and 11 infusions and FIX consumption was between 0 and 444.1 IU/kg. Six patients undergoing surgery were discharged from the surgical treatment site on the same day.
Routine Prophylaxis
Of the 63 subjects treated with IDELVION, twenty-three PTPs received IDELVION only for the treatment of bleeding episodes during the first 6 months of the study. Nineteen of these PTPs switched to once weekly prophylaxis with additional median duration of 10 months.
Based on the analysis of the 19 subjects treated with IDELVION for on-demand therapy and weekly prophylaxis, the median annualized spontaneous bleeding rate (AsBR) during prophylaxis treatment was 0.7 (range: 0 to 4.2), as compared to 15.4 (range: 2 to 39.5) during on-demand treatment. Based on the Poisson model, prophylaxis treatment with IDELVION resulted in a 93% reduction in the annualized spontaneous bleeding rate.
The median annualized bleeding rate (total ABR – spontaneous and traumatic) during prophylaxis treatment was 1.6; (range: 0 to 21.1), as compared to 19.2; (range: 2 to 46.1) during on demand treatment. Based on the Poisson model, prophylaxis treatment with IDELVION resulted in an 88% reduction in the annualized bleeding rate.
| Bleeding Episode Etiology | On-demand (n=19)* | Weekly Prophylaxis (n=19)* | Percent Reduction with Prophylaxis (n=19)* |
|---|---|---|---|
| IQR=interquartile range, defined for 25th percentile and 75th percentile; SD=standard deviation; Subjects evaluable for efficacy are subjects who received at least one dose of on-demand treatment, and one dose of prophylaxis treatment. | |||
| Spontaneous | |||
| Mean (SD) | 14.6 (8.42) | 0.9 (1.17) | 93.5 (8.03) |
| Median | 15.4 | 0.7 | 95.9 |
| IQR | 8.0, 18.0 | 0, 1.6 | 89.0, 100 |
| Range | 2.0, 39.5 | 0, 4.2 | 75.2, 100 |
| Total† | |||
| Mean (SD) | 20.8 (9.19) | 2.9 (4.79) | 88.0 (14.06) |
| Median | 19.2 | 1.6 | 90.9 |
| IQR | 16.7, 25.8 | 0, 4.3 | 81.2, 100 |
| Range | 2.0, 46.1 | 0, 21.1 | 54.3, 100 |
Forty subjects received weekly routine prophylaxis. Thirty-seven subjects completed 6 months of once weekly prophylaxis. Of these, 21 subjects switched to a 14-day interval with 50-75 IU/kg of IDELVION with a median duration of 12.7 months. Prior to switching, these 21 subjects were well controlled with IDELVION (did not require dose adjustments or experience spontaneous bleeding 1 month prior to switch and were maintained on a prophylaxis dose of ≤40 IU/kg every 7 days).
The median AsBRs for the 21 subjects treated with weekly and 14-day prophylaxis were zero (range: 0 to 4.5) and zero (range: 0 to 7.3), respectively (summarized in Table 8). In addition, the median AsBRs for the 7 subjects treated with weekly and 10-day prophylaxis were zero (range: 0 to 0) and zero (range: 0 to 0.9), respectively.
| Bleeding Episode Etiology | Weekly Prophylaxis (n=21)* | 14 day Prophylaxis (n=21)* |
|---|---|---|
| IQR = interquartile range; SD = Standard deviation | ||
| Spontaneous | ||
| Mean (SD) | 0.28 (1.01) | 1.07 (2.1) |
| Median | 0 | 0 |
| IQR | 0, 0 | 0, 1 |
| Range | 0, 4.5 | 0, 7.3 |
* Based on a matched pairs design
Routine Prophylaxis and Control of Bleeding in PTPs <12 Years
Safety, efficacy, and pharmacokinetics of IDELVION have been evaluated in previously treated pediatric patients (PTPs) ranging from one (1) to <12 years of age. A total of 27 males, 12 patients <6 years of age and 15 patients between 6 to <12 years of age, received IDELVION for prophylaxis and control of bleeding episodes. All 27 subjects received weekly prophylaxis treatment with IDELVION for a mean time on study of 13.1 months (range: 9, 18 months).
The routine weekly regimen with rIX-FP was effective in the prophylaxis of bleeding episodes. The median (Q1, Q3) ABR (total bleeding episodes, including untreated) and annualized spontaneous bleeding rate (AsBR) during prophylaxis treatment in the efficacy population were 3.41 [1.18,7.44] and 0 [0, 1.34] bleeding episodes/subject/year, respectively. The mean ABR was 4.55 bleeding episodes/year/subject and the mean AsBR was 0.79 based on the total of both treated and untreated bleeding episodes. The target joints (defined as 3 or more spontaneous bleeds into a single joint within a consecutive 6-months period) reported in 3 subjects prior to study entry were resolved during the study. All subjects maintained a weekly routine prophylaxis regimen throughout.
Of the 106 bleeding episodes, the majority (94;89%) was treated with single injection, 103 (97%) were treated with 1-2 injections. Hemostatic efficacy at resolution of a bleed was rated excellent or good in 96% of all treated bleeding episodes.
IDELVION is supplied as a lyophilized powder in single-dose vials containing the labeled amount of Factor IX activity, expressed in international units (IU).
IDELVION is packaged with 2.5 mL (for reconstitution of 250, 500 or 1000 IU vials) or 5 mL (for reconstitution of 2000 or 3500 IU vials) of Sterile Water for Injection, USP, one Mix2Vial filter transfer set, and one sterile alcohol swab. Components are not made with natural rubber latex.
| Nominal Strength (International Units) | Fill Size Color Indicator | Kit NDC |
|---|---|---|
| 250 | Orange | 69911-864-02 |
| 500 | Blue | 69911-865-02 |
| 1000 | Green | 69911-866-02 |
| 2000 | Purple | 69911-867-02 |
| 3500 | Yellow | 69911-869-02 |
Storage and Handling
Manufactured by:
CSL Behring GmbH
35041 Marburg, Germany
for:
CSL Behring Lengnau AG
Biotech Innovation Park
2543 Lengnau, Switzerland
US License No. 2009
Distributed by:
CSL Behring LLC
Kankakee, IL 60901 USA
IDELVION® is manufactured under a license by Novozymes Biopharma A/S, Bagsvaerd, Denmark.
Mix2Vial® is a registered trademark of West Pharma. Services IL, Ltd., a subsidiary of West Pharmaceutical Services, Inc.
IDELVION® (eye del' vee on),
Coagulation Factor IX (Recombinant), Albumin Fusion Protein
This leaflet summarizes important information about IDELVION. Please read it carefully before using IDELVION. This information does not take the place of talking with your healthcare provider, and it does not include all of the important information about IDELVION. If you have any questions after reading this, ask your healthcare provider.
What is IDELVION?
IDELVION, Coagulation Factor IX (Recombinant), Albumin Fusion Protein is an injectable medicine used to replace clotting factor (Factor IX) that is missing in people with hemophilia B (also called congenital Factor IX deficiency or Christmas disease). Hemophilia B is an inherited bleeding disorder that prevents blood from clotting normally. IDELVION is used in children and adults with hemophilia B to control and prevent bleeding episodes. Your healthcare provider may give you IDELVION when you have surgery. IDELVION can reduce the number of bleeding episodes when used regularly (prophylaxis).
Who should not use IDELVION?
You should not use IDELVION if you:
Tell your healthcare provider if you have had an allergic reaction to any Factor IX product prior to using IDELVION.
Tell your healthcare provider if you are pregnant or breast-feeding because IDELVION may not be right for you.
What should I tell my healthcare provider before using IDELVION?
You should tell your healthcare provider if you:
How should I administer IDELVION?
What are the possible side effects of IDELVION?
Allergic and hypersensitivity reactions have been reported with IDELVION. Call your healthcare provider right away and stop treatment if you get a rash or hives, itching, tightness of the chest or throat, difficulty breathing, light-headedness, dizziness, nausea, or decrease in blood pressure.
Your body can make antibodies, called inhibitors, against Factor IX which may stop IDELVION from working properly. Your healthcare provider may need to test your blood for inhibitors from time to time.
IDELVION may increase the risk of forming abnormal blood clots in your body, especially if you have risk factors for developing blood clots. Call your healthcare provider if you have chest pain, difficulty breathing, leg tenderness or swelling.
The most common side effects of IDELVION are headache and dizziness.
This is not the only side effect possible with IDELVION. To learn more, talk to your healthcare provider or pharmacist. Tell your healthcare provider about any side effect that bothers you or does not go away.
What are the IDELVION dosage strengths?
IDELVION comes in five different dosage strengths: 250, 500, 1000, 2000, or 3500 IU. The actual strength of IDELVION is printed on the carton and vial label. The labeling of the five dosage strengths are color-coded as provided in Table 1 below.
| Fill Size Color Indicator | Nominal Strength |
|---|---|
| Orange | 250 IU |
| Blue | 500 IU |
| Green | 1000 IU |
| Purple | 2000 IU |
| Yellow | 3500 IU |
Always check the actual dosage strength printed on the label to make sure you are using the strength prescribed by your healthcare provider.
How should I store IDELVION?
What else should I know about IDELVION?
For intravenous use after reconstitution only.
Do not attempt to do an intravenous injection unless you have been taught how by your healthcare provider or hemophilia center.
Always follow the specific instructions given by your healthcare provider. The steps listed below are general guidelines for using IDELVION. If you are unsure of the instructions, call your healthcare provider before using IDELVION. Call your healthcare provider right away if bleeding is not controlled after using IDELVION. Your healthcare provider will prescribe the dose that you should take. You may need to have blood tests from time to time. Talk to your healthcare provider before traveling. Dispose of all unused solution, empty vial(s), and other used medical supplies in an appropriate medical waste container.
IDELVION Reconstitution Instructions
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Administration (intravenous injection)
Resources at CSL Behring available to the patient:
For Adverse Reaction Reporting contact:
CSL Behring Pharmacovigilance Department at 1-866-915-6958
Contact CSL Behring to receive more product information:
Patient Support Hotline at 1-800-676-4266
For more information, visit www.IDELVION.com
Manufactured by:
CSL Behring GmbH
35041 Marburg, Germany
for:
CSL Behring Lengnau AG
Biotech Innovation Park
2543 Lengnau, Switzerland
US License No. 2009
Distributed by:
CSL Behring LLC
Kankakee, IL 60901 USA
IDELVION® is manufactured under a license by Novozymes Biopharma A/S, Bagsvaerd, Denmark.
Mix2Vial® is a registered trademark of West Pharma. Services IL, Ltd., a subsidiary of West Pharmaceutical Services, Inc.
Revised: 6/2023
NDC 69911-864-02
250 IU Range
IDELVION®
Coagulation Factor IX (Recombinant),
Albumin Fusion Protein
One single-use vial containing lyophilized powder
for reconstitution.
For Intravenous Administration Only
CSL Behring
NDC 69911-865-02
500 IU Range
IDELVION®
Coagulation Factor IX (Recombinant),
Albumin Fusion Protein
One single-use vial containing lyophilized powder
for reconstitution.
For Intravenous Administration Only
CSL Behring
NDC 69911-866-02
1000 IU Range
IDELVION®
Coagulation Factor IX (Recombinant),
Albumin Fusion Protein
One single-use vial containing lyophilized powder
for reconstitution.
For Intravenous Administration Only
CSL Behring
NDC 69911-867-02
2000 IU Range
IDELVION®
Coagulation Factor IX (Recombinant),
Albumin Fusion Protein
One single-use vial containing lyophilized powder
for reconstitution.
For Intravenous Administration Only
CSL Behring
NDC 69911-869-02
3500 IU Range
IDELVION®
Coagulation Factor IX (Recombinant),
Albumin Fusion Protein
One single-use vial containing lyophilized powder
for reconstitution.
For Intravenous Administration Only
CSL Behring
| RxCUI | RxNorm string | TTY | SPL version |
|---|---|---|---|
| 1743994 | albutrepenonacog alfa 1 UNT Injection | PSN | 12 |
| 1743999 | IDELVION 1 UNT Injection | PSN | 12 |
| 1743999 | albutrepenonacog alfa 1 UNT Injection [IDELVION] | SBD | 12 |
| 1743994 | albutrepenonacog alfa 1 UNT Injection | SCD | 12 |
| 1743994 | coagulation factor IX (recombinant human), albumin fusion protein 1 UNT Injection | SY | 12 |
| 1743999 | IDELVION 1 UNT Injection | SY | 12 |
| Package NDC | Product | Description | Form | Quantity | Strength | SPL version |
|---|---|---|---|---|---|---|
| 69911-864-02 | IDELVION | 1 in 1 CARTON | KIT | 1 | 12 | |
| 69911-874-01 | IDELVION | 2.5 mL in 1 VIAL, SINGLE-USE | INJECTION, POWDER, LYOPHILIZED, | 2.5 mL | 250 [iU] in 2.5mL | 12 |
| 69911-865-02 | IDELVION | 1 in 1 CARTON | KIT | 1 | 12 | |
| 69911-875-01 | IDELVION | 2.5 mL in 1 VIAL, SINGLE-USE | INJECTION, POWDER, LYOPHILIZED, | 2.5 mL | 500 [iU] in 2.5mL | 12 |
| 69911-866-02 | IDELVION | 1 in 1 CARTON | KIT | 1 | 12 | |
| 69911-876-01 | IDELVION | 2.5 mL in 1 VIAL, SINGLE-USE | INJECTION, POWDER, LYOPHILIZED, | 2.5 mL | 1000 [iU] in 2.5mL | 12 |
| 69911-867-02 | IDELVION | 1 in 1 CARTON | KIT | 1 | 12 | |
| 69911-877-01 | IDELVION | 5 mL in 1 VIAL, SINGLE-USE | INJECTION, POWDER, LYOPHILIZED, | 5 mL | 2000 [iU] in 5mL | 12 |
| 69911-869-02 | IDELVION | 1 in 1 CARTON | KIT | 1 | 12 | |
| 69911-879-01 | IDELVION | 5 mL in 1 VIAL, SINGLE-USE | INJECTION, POWDER, LYOPHILIZED, | 5 mL | 3500 [iU] in 5mL | 12 |
| NDC | Dashboard title | SPL version | Validation | Dashboard ZIP |
|---|---|---|---|---|
| 69911-765 | IDELVION (COAGULATION FACTOR IX RECOMBINANT HUMAN) KIT [CSL BEHRING LENGNAU AG] | 12 | Unmatched | 20230706_f74301bf-95e2-44ab-a8b6-98aa07b04683.zip |
| 69911-864 | IDELVION (COAGULATION FACTOR IX RECOMBINANT HUMAN) KIT [CSL BEHRING LENGNAU AG] | 12 | Current NDC, Legacy NDC, 2 package rows | 20230706_f74301bf-95e2-44ab-a8b6-98aa07b04683.zip |
| 69911-865 | IDELVION (COAGULATION FACTOR IX RECOMBINANT HUMAN) KIT [CSL BEHRING LENGNAU AG] | 12 | Current NDC, Legacy NDC, 2 package rows | 20230706_f74301bf-95e2-44ab-a8b6-98aa07b04683.zip |
| 69911-866 | IDELVION (COAGULATION FACTOR IX RECOMBINANT HUMAN) KIT [CSL BEHRING LENGNAU AG] | 12 | Current NDC, Legacy NDC, 2 package rows | 20230706_f74301bf-95e2-44ab-a8b6-98aa07b04683.zip |
| 69911-867 | IDELVION (COAGULATION FACTOR IX RECOMBINANT HUMAN) KIT [CSL BEHRING LENGNAU AG] | 12 | Current NDC, Legacy NDC, 2 package rows | 20230706_f74301bf-95e2-44ab-a8b6-98aa07b04683.zip |
| 69911-869 | IDELVION (COAGULATION FACTOR IX RECOMBINANT HUMAN) KIT [CSL BEHRING LENGNAU AG] | 12 | Current NDC, Legacy NDC, 2 package rows | 20230706_f74301bf-95e2-44ab-a8b6-98aa07b04683.zip |
| 69911-874 | IDELVION (COAGULATION FACTOR IX RECOMBINANT HUMAN) KIT [CSL BEHRING LENGNAU AG] | 12 | Unmatched | 20230706_f74301bf-95e2-44ab-a8b6-98aa07b04683.zip |
| 69911-875 | IDELVION (COAGULATION FACTOR IX RECOMBINANT HUMAN) KIT [CSL BEHRING LENGNAU AG] | 12 | Unmatched | 20230706_f74301bf-95e2-44ab-a8b6-98aa07b04683.zip |
| 69911-876 | IDELVION (COAGULATION FACTOR IX RECOMBINANT HUMAN) KIT [CSL BEHRING LENGNAU AG] | 12 | Unmatched | 20230706_f74301bf-95e2-44ab-a8b6-98aa07b04683.zip |
| 69911-877 | IDELVION (COAGULATION FACTOR IX RECOMBINANT HUMAN) KIT [CSL BEHRING LENGNAU AG] | 12 | Unmatched | 20230706_f74301bf-95e2-44ab-a8b6-98aa07b04683.zip |
| 69911-879 | IDELVION (COAGULATION FACTOR IX RECOMBINANT HUMAN) KIT [CSL BEHRING LENGNAU AG] | 12 | Unmatched | 20230706_f74301bf-95e2-44ab-a8b6-98aa07b04683.zip |
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 69911-864-02 | EA - Each | 69911-864 | cd7600f3-6ba9-4486-a156-7a05f5f4501a | 1 | 2016-04-04 |
| 69911-865-02 | EA - Each | 69911-865 | 3b12bc0f-bd83-4330-9a45-dd3dc2e49ba6 | 1 | 2016-04-04 |
| 69911-866-02 | EA - Each | 69911-866 | f109cda1-f44c-4ca5-86e5-de345664f7eb | 1 | 2016-04-04 |
| 69911-867-02 | EA - Each | 69911-867 | 66420fca-fcb0-4fb9-8e4e-35cb95a05bdc | 1 | 2016-04-04 |
| 69911-869-02 | EA - Each | 69911-869 | 0bfa3d53-098c-4fb6-b325-a4ba04027215 | 1 | 2018-08-13 |
Every source-derived product name is available through these pages.
| BLA | Proprietary name | Proper name | License type | Status | Latest source |
|---|---|---|---|---|---|
| 125582 | Idelvion | Coagulation Factor IX (Recombinant), Albumin Fusion Protein | 351(a) | Rx | 2026-09-01 |
Every source-derived ingredient row is available through these pages.
Adverse event summaries are temporarily unavailable. Other product information remains available.
