Brand Name
Sevenfact
Generic Name
VIIa
View Brand Information FDA approval date: April 01, 2023
Form: Kit
What is Sevenfact (VIIa)?
SEVENFACT [coagulation factor VIIa -jncw] is indicated for the treatment and control of bleeding episodes occurring in adults and adolescents with hemophilia A or B with inhibitors. Limitation of Use: SEVENFACT is not indicated for the treatment of patients with congenital Factor VII deficiency. SEVENFACT [coagulation factor VIIa -jncw] is a coagulation factor VIIa concentrate indicated for the treatment and control of bleeding episodes occurring in adults and adolescents with hemophilia A or B with inhibitors . Limitation of Use: SEVENFACT is not indicated for treatment of congenital factor VII deficiency.
Approved To Treat
Save this treatment for later
Not sure about your diagnosis?
Related Clinical Trials
aPCC and Emicizumab Safety Study in Congenital Hemophilia A Patients With Inhibitors (SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis)
Summary: The purpose of the aPCC-emicizumab safety study is to investigate the hemostatic efficacy as measured by thrombin generation, of a low personalized dose of aPCC (FEIBA) in children and adults with hemophilia A and inhibitors on emicizumab prophylaxis.
MOdern Treatment of Inhibitor-PositiVe PATiEnts With Haemophilia A - An International Observational Study
Summary: This is a non-interventional, multicenter, observational, international study in male persons with haemophilia A who have developed inhibitors to any replacement coagulation factor VIII (FVIII) product. The purpose of the study is to capture different approaches in the management of persons with haemophilia A and FVIII inhibitors, document current immune tolerance induction approaches, and evaluat...
Recombinant Factor VIIa (rFVIIa) for Acute Hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial
Summary: The objective of the rFVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial is to establish the first treatment for acute spontaneous intracerebral hemorrhage (ICH) within a time window and subgroup of patients that is most likely to benefit. The central hypothesis is that rFVIIa, administered within 120 minutes from stroke onset with an identified subgroup of patients m...
Related Latest Advances
Brand Information
Sevenfact (Coagulation Factor VIIa Recombinant Human)
WARNING: THROMBOSIS
●Serious arterial and venous thrombotic events may occur following administration of SEVENFACT®.[See Warnings and Precautions (5.1)]
●Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive SEVENFACT®.
● Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis.
1INDICATIONS AND USAGE
SEVENFACT
Limitation of Use: SEVENFACT is not indicated for the treatment of patients with congenital Factor VII deficiency.
2DOSAGE AND ADMINISTRATION
For intravenoususe after reconstitutiononly.
2.1Dose
- Dose and duration of treatment depend on the location and severity of the bleeding, need for urgent hemostasis, frequency of administration, and known patient responsiveness to FVIIa-containing bypassing agents during prior bleeding events. Treatment with SEVENFACT should be initiated as soon as a bleeding event occurs.
- The dose, frequency, and duration of SEVENFACT therapy should be based on the patient’s clinical response and hemostasis evaluation.
- The use of laboratory assessment(s) of coagulation (PT/INR, aPTT, FVII:C) does not necessarily correlate with or predict the hemostatic effectiveness of SEVENFACT.
- Maximum tolerated doses have not been determined for SEVENFACT, and cumulative daily doses greater than 900 mcg/kg, which may be associated with greater risk of thromboembolic complications, have not been studied.
- Dose adjustment may be required if the patient has received other procoagulant therapies prior to treatment with SEVENFACT.
Based on the clinical trial program for SEVENFACT, the recommended initial dose should be adjusted based on the criteria provided in Table 1.
2.2Reconstitution
- Follow the procedures below for reconstitution of SEVENFACT.
- Calculate the amount of SEVENFACT required and select the appropriate SEVENFACT packages containing the matching pre-filled syringe of sterile Water for Injection, and the vial adapters.
- Reconstitute each vial with the pre-filled syringe provided with each vial of SEVENFACT.
Overview ofSEVENFACTPackage:
Figure1Vial with SEVENFACT lyophilized powder
LyophilizedPowder Drug Vial
Figure2Syringe plunger rod and pre-filled syringe with Water for Injection diluent
Syringe Plunger RodPre-filled syringe with Diluent
Figure3SEVENFACT 1 mgand 2 mgvial adapter and SEVENFACT 5 mg vial adapter
Vial Adapters* and Packaging
1 mgand 2 mgvial adapter 5 mg vial adapter
*Note: Each SEVENFACT kit will contain only one vial adapter.
The instructions below serve as a general guideline for reconstitution of SEVENFACT.
Reconstitution:
1. Based on the prescribed dose, take out the number of SEVENFACT kits (each kit containing one vial of SEVENFACT
2. Always use aseptic technique. Wash your hands with soap and water and dry them using a clean towel or air dry.
3. Take out the contents of one kit and one alcohol swab. Place items on a clean surface.
4. Inspect all contents of the kit. Make sure each vial has a matching colored syringe.
5. Bring SEVENFACT (lyophilized powder) and the specified pre-filled syringe (diluent) to room temperature. The specified volume of diluent corresponding to the amount of SEVENFACT is as follows:
1 mg (1000 micrograms) vial + 1.1 mL Water for Injection diluent in pre-filled syringe
2 mg (2000 micrograms) vial + 2.2 mL Water for Injection diluent in pre-filled syringe
5 mg (5000 micrograms) vial + 5.2 mL Water for Injection diluent in pre-filled syringe
6. Remove the plastic cap from the SEVENFACT vials to expose the central portion of the rubber stopper. Cleanse the rubber stoppers with an alcohol swab and allow to dry prior to use.
7. Peel back the protective paper from the vial adapter. Do not remove the vial adapter from the package.
8. Place the SEVENFACT vial on a flat surface. While holding the vial adapter package, place the vial adapter over the SEVENFACT vial and press down firmly on the package until the vial adapter spike breaks through the rubber stopper.
9. Lightly squeeze the plastic cover and lift up to remove it from the vial adapter. Note: the 5 mg vial adapter may not sit flat against the vial, but it is fully functional.
10. Remove the syringe cap from the pre-filled syringe by holding the syringe body with one hand to unscrew the syringe cap (turn to the left).
11. While holding the edges of the vial adapter, screw on the pre-filled syringe (turn to the right) a few turns until it starts to tighten.
12. Insert the plunger rod into the syringe, then screw a few turns (turn to the right) so that the plunger rod is attached to the gray rubber stopper in the syringe.
13. Push the plunger rod to slowly inject all the diluent into the vial. Keep the plunger rod pressed down and swirl the vial gently until the powder is dissolved.
14. The reconstituted solution is clear to slightly opaque. All powder must be mixed with no particles floating in the liquid.
15. Without withdrawing any drug back into the syringe, unscrew the syringe from the vial adapter (turn to the left) until it is completely detached.
16. Withdraw the liquid drug from the vial(s), using an infusion syringe provided by the pharmacy; the syringe should be large enough to hold the prescribed dose.
17. The reconstituted solution should be stored in the vial at room temperature, but can be stored between 36
2.3Administration
For Intravenous Use Only.
- Visually inspect the reconstituted solution for particulate matter and discoloration prior to administration. Do not use if particulate matter or discoloration is observed.
- Do not freeze reconstituted solution or store it in a syringe.
- SEVENFACT must be infused within 4 hours after reconstitution.
- SEVENFACT should be infused over 2 minutes or less as a bolus intravenous infusion.
- Do not mix with other infusion solutions.
- Any unused solution should be discarded 4 hours after reconstitution.
3DOSAGE FORMS AND STRENGTHS
SEVENFACT is a white to off-white lyophilized powder for reconstitution in a colorless solution for injection. It is supplied in single-dose vial sizes containing 1 mg, 2 mg or 5 mg of coagulation factor VIIa (recombinant)-jncw.
The diluent for reconstitution of SEVENFACT is supplied in single-dose prefilled glass syringes containing 1.1 mL, 2.2 mL or 5.2 mL sterile Water for Injection. It is a clear colorless solution.
After reconstitution with the appropriate volume of Water for Injection diluent, each mL of SEVENFACT contains 1 mg per mL of coagulation factor VIIa (recombinant)-jncw (1,000 micrograms per mL).
4CONTRAINDICATIONS
SEVENFACT is contraindicated in
- known allergy to rabbits or rabbit proteins. Exposure to SEVENFACT in these patients can result in severe hypersensitivity reaction.
- patients with severe hypersensitivity reaction to SEVENFACT or any of its components. Exposure to SEVENFACT in these patients can result in severe hypersensitivity reaction.
5ADVERSE REACTIONS
The most common adverse reactions (incidence ≥1%) reported in clinical trials for SEVENFACT were headache, dizziness, infusion-site discomfort, infusion-site hematoma, infusion-related reaction, and fever.
5.1Clinical Trials Experience
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 the clinical trials of another drug and may not reflect the rates observed in practice.
In two studies of SEVENFACT in patients with Hemophilia A or B with or without inhibitors, 42 subjects (27 subjects in Study 1 and 15 subjects in Study 2) have been exposed to SEVENFACT.
Study 1: The safety of SEVENFACT has been evaluated in a safety and efficacy study of 27 subjects with Hemophilia A or B with inhibitors, which included treatment of 468 bleeding episodes. As described in Table 2, a total of seven adverse reactions were observed in two subjects (7.4%) treated with SEVENFACT. One episode of fever occurred in a 12-year-old subject, lasted two days, and was managed symptomatically.
Study 2: In a study with 15 subjects evaluating the safety and pharmacokinetics of three escalating doses of SEVENFACT (25 mcg/kg, 75 mcg/kg and 225 mcg/kg), a total of three (20%) subjects experienced four adverse reactions (Table 2).
One subject developed an infusion reaction immediately following the infusion of the first dose of 75 mcg/kg; the reaction lasted 45 minutes. Signs and symptoms included flushing, chest tightness, shakiness, transient tachycardia, and mild hypotension. Symptoms resolved without any intervention and did not recur with subsequent administration at 225 mcg/kg dose.
Adverse reactions reported in the two clinical studies are shown in Table 2.
5.2Immunogenicity
In Study 1, two out of 27 subjects had a positive screening assay for anti-SEVENFACT antibody at baseline, prior to exposure to SEVENFACT,
In Study 2, five of 15 subjects tested positive for anti-SEVENFACT antibody using a screening assay. The confirmatory assay was negative for all subjects at all time points.
No subject developed anti-rabbit milk protein antibodies during treatment with SEVENFACT.
The detection of antibodies 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, comparison of the incidence of antibodies to SEVENFACT with the incidence of antibodies to other products may be misleading.
6DRUG INTERACTIONS
Clinical experience with pharmacologic use of FVIIa-containing products indicates an elevated risk of serious thrombotic events when used simultaneously with activated prothrombin complex concentrates.
7OVERDOSAGE
There have been no reports of overdosage with SEVENFACT. Doses greater than 900 mcg/kg/day have not been studied. Doses greater than 900 mcg/kg per 24 hours may be associated with an increased risk of thromboembolic events.
8DESCRIPTION
SEVENFACT is a sterile, white to off-white lyophilized powder in a single-dose vial containing either 1 mg, 2 mg or 5 mg of coagulation factor VIIa (recombinant)-jncw as the active ingredient. SEVENFACT is to be reconstituted with Sterile Water for Injection in a pre-filled syringe supplied with the product. The reconstituted product is a clear to slightly opaque solution of coagulation factor VIIa (recombinant)-jncw at a concentration of 1 mg of protein per mL with a pH of approximately 6.0. SEVENFACT is formulated with arginine, isoleucine, citrate, glycine, lysine and polysorbate 80. It does not contain any antimicrobial preservatives nor human or bovine plasma-derived proteins.
The active ingredient in SEVENFACT, activated coagulation Factor VII, is a glycoprotein of 406 amino acids with a molecular weight of approximately 50 kilodaltons. The amino acid sequence of activated coagulation Factor VII is identical to that of human plasma-derived Factor VIIa. It is >99% pure with a nominal specific activity of 45,000 IU/mg of protein when tested against the World Health Organization international standard for human Factor VIIa activity.
SEVENFACT is produced by recombinant DNA technology using genetically engineered rabbits into which the DNA coding sequence for human Factor VII has been introduced. Human Factor VII is expressed in the rabbit mammary gland and secreted into the milk. During purification and processing, Factor VII is enzymatically converted to activated Factor VII. The manufacturing process of SEVENFACT includes specific steps to reduce impurities. SEVENFACT may contain trace amounts of rabbit proteins. The purification process also includes steps that are validated to inactivate or remove viruses, such as Xenotropic murine leukemia virus (X-MuLV), bovine viral diarrhea virus (BVDV), Pseudorabies virus (PRV), Feline Calicivirus (FCV), and Porcine Parvovirus (PPV).
9CLINICAL STUDIES
The efficacy and safety of SEVENFACT for treatment of bleeding episodes was evaluated in Study 1. Twenty-seven subjects with hemophilia A or B with inhibitors were treated for 468 bleeding events, of which 465 were mild or moderate and three were severe bleeding events. Of the 27 subjects, 5 subjects were 12 to < 18 years of age and they experienced 79 bleeding events. The study was a global, multicenter, randomized, open-label, crossover of two initial dose regimens. Subjects were male, predominantly Caucasian (93%), with a mean age of 31 (range 12-54) years and median of 10 (3-50) bleeding episodes in six months prior to study enrollment. Overall, target joint(s)/bleeding site(s) were reported in 63% of subjects at study entry.
All doses of SEVENFACT were given at home or in clinic.
Of the 468 bleeding events in diverse anatomic locations that were treated, 82% were spontaneous and the remaining (18%) were traumatic bleeding episodes; 465 were mild or moderate bleeding events and 3 were severe (refer to Table 5). The majority (98%) of bleeding events were treated at home, with 88% treated within one hour of recognition of bleeding.
Treatment Regimens forMildorModerate Bleeding Episodes
For mild to moderate bleeding episodes, subjects were randomized to one of two initial dose regimens of SEVENFACT:
- 75 mcg/kg followed by subsequent doses of 75 mcg/kg every 3 hours as necessary to achieve hemostatic efficacy. A total of 8 administrations were allowed in this dose regimen.
- 225 mcg/kg dose followed 9 hours later with 75 mcg/kg doses every 3 hours as necessary to achieve hemostatic efficacy. A total of 6 administrations were allowed in this dose regimen.
Treatment with SEVENFACT was discontinued when bleeding persisted 24 hours after the first administration of SEVENFACT.
In Study 1, subjects were randomized to one of two initial dosing regimens and continued on the dose regimen for three months, after which the subjects were crossed over to the other dose regimen for three months.
Treatment Regimens for Severe Bleeding Episodes
Patients in the randomized study who experienced a severe bleed were administered the initial dose of 225 mcg/kg SEVENFACT at home, and were required to receive subsequent treatments at 75 mcg/kg every two hours in a hospital or hemophilia treatment center (HTC), if additional doses were considered necessary for treatment of ongoing bleeding. If response to treatment after the first or any subsequent administrations of study drug were satisfactory (i.e., efficacy assessment was rated as “good” or “excellent”), the dosing interval was changed from two hours to three hours for 1 to 2 days, after which the interval could be increased to 4 to 12 hours, depending on the severity of the bleeding episode, for as long as needed.
Bleeding Assessment
The primary endpoint of the study was successful treatment of mild or moderate bleeding episode at 12 hours after initial SEVENFACT dose administration. Success was defined by a combination of the following: subject’s response of “good” or “excellent” using a 4-point hemostatic efficacy scale (presented in Table 4), no further treatment with SEVENFACT beyond the 12-hour time point, no other hemostatic treatment needed for the bleeding episode, no administration of blood products, and no increase in pain beyond 12 hours.
The primary efficacy analysis compared hemostatic efficacy of each dosing regimen with a prespecified objective performance criterion (OPC) of 55%. This OPC was based on historical data for hemostatic efficacy of bypassing agents. The study was powered to detect a 15% improvement over OPC for each dosing regimen. Results of the primary efficacy analysis are shown in Table 5.
Of the 465 mild or moderate bleeding episodes, 17 bleeding events were not evaluable due to missing a hemostatic efficacy assessment at 12 hours.
The proportion of mild or moderate bleeding events with hemostatic efficacy at 12 hours was 82% in the 75 mcg/kg dose regimen group and was 91% in the 225 mcg/kg dose regimen group.
Hemostatic efficacy was evaluated in 79 bleeding events in the five adolescent subjects: for the 75 mcg/kg dose regimen, hemostatic efficacy was 93% (95% CI; 81%- 99%) and for the 225 mcg/kg dose regimen, it was 91% (95% CI; 77%-98%), with the confidence intervals given by the Clopper-Pearson exact method.
The median and mean (SD) numbers of administrations per mild or moderate bleeding episode were 2.0 and 2.5 (1.75) for the 75 mcg/kg dose regimen and 1.0 and 1.4 (0.96) for the 225 mcg/kg dose regimen.
The median time to attain good or excellent assessment by the patient was 6 hours for the 75 mcg/kg dose regimen and 3 hours for the 225 mcg/kg dose regimen.
There were 3 severe bleeding episodes, of which one was a traumatic intramuscular bleeding episode and two were spontaneous bleeding episodes in the right hip and kidney. Hemostasis was achieved at 12 hours in the three severe bleeding events. One severe bleed was treated with three 225 mcg/kg doses administered every 6 hours, which was a deviation from the study protocol-specified dosing. The remaining 2 subjects were treated with 1 and 5 doses of SEVENFACT respectively.
No subject received any alternative therapy prior to 24 hours. In addition, 97.6% of bleeding episodes treated with the 75 mcg/kg dose regimen, and 99.5% of bleeding episodes treated with the 225 mcg/kg dose regimen, did not require treatment with alternative bypassing agents.
10HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
- SEVENFACT [coagulation factor VIIa (recombinant)-jncw], is supplied as a room temperature stable, white to off-white, lyophilized powder in single-dose vials, one vial per carton. The diluent for reconstitution of SEVENFACT is Water for Injection supplied as a clear colorless solution in a pre-filled syringe.
- Single 1 mg, 2 mg or 5 mg vials of SEVENFACT are available in packages as indicated below.
- The SEVENFACT vials are made of glass, closed with a bromobutyl rubber stopper (not made with natural rubber latex), and sealed with an aluminum cap.
- The pre-filled diluent syringes are made of glass, with a siliconized bromobutyl rubber plunger (not made with natural rubber latex).
Storage and Handling
- Prior to reconstitution, the SEVENFACT kit should be stored at room temperature but can be stored between 36°F to 86°F (2°C to 30°C), protected from light in the product package. Do not freeze.
- After reconstitution, SEVENFACT should be stored at room temperature but can be stored between 36°F to 86°F (2°C to 30°C), for up to 4 hours. Do not freeze or store in syringes.
11PATIENT COUNSELING INFORMATION
Advise patients:
- to read the FDA-approved patient labeling (
- about the early signs of hypersensitivity reactions and to seek medical help if the following occur:
- about the signs of thrombosis and to seek medical help if the following occur:
Revised: June 23, 2024
Forinformation contact:
Call: 855.718.HEMA (4362)
Fax: 855.721.HEMA (4362)
Email: medinfo@hemabio.com
Call: 855.718.HEMA (4362)
Fax: 855.721.HEMA (4362)
Email: medinfo@hemabio.com
Manufactured by:
Laboratoire Français du Fractionnement et des Biotechnologies S.A. (LFB S.A.)
Puteaux, 92800
France
Laboratoire Français du Fractionnement et des Biotechnologies S.A. (LFB S.A.)
Puteaux, 92800
France
U.S. License Number: 2061
Distributedby:
HEMA Biologics
Louisville, KY 40241
HEMA Biologics
Louisville, KY 40241
12PRINCIPAL DISPLAY PANEL
NDC 71127-1000-1
SEVENFACT
For intravenous use only
Dosage and Administration: Read Package Insert
CONTENTS:
Not made with natural rubber latex
Rx only
LFB
HEMA Biologics
13PRINCIPAL DISPLAY PANEL
NDC 71127-2000-1
SEVENFACT
For intravenous use only
Dosage and Administration: Read Package Insert
CONTENTS:
Rx only
LFB
HEMA Biologics
14PRINCIPAL DISPLAY PANEL
NDC 71127-5000-1
SEVENFACT
For intravenous use only
Dosage and Administration: Read Package Insert
CONTENTS:
Rx only
LFB
HEMA Biologics
15PRINCIPAL DISPLAY PANEL
NDC 71127-1100-1
16PRINCIPAL DISPLAY PANEL
NDC 71127-2100-1
17PRINCIPAL DISPLAY PANEL
NDC 71127-5100-1
18PRINCIPAL DISPLAY PANEL
NDC 71127-2200-1
LOT 000000000AB
EXP MMM0000
Manufactured by LFB S.A. Puteaux, 92800, France
19PRINCIPAL DISPLAY PANEL
NDC 71127-1200-1
LOT 000000000A
EXP MMM0000
Manufactured by LFB S.A.
20PRINCIPAL DISPLAY PANEL
NDC 71127-5200-1
LOT 000000000AB
EXP MMM0000
Manufactured by LFB S.A. Puteaux, 92800, France
