Recombinant factor VIIa (rfVIIa) is a form of blood

factor VII Coagulation factor VII (, formerly known as proconvertin) is a protein involved in coagulation and, in humans, is encoded by gene ''F7''. It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, ...

that has been manufactured via

recombinant technology Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be found ...

. It is administered via an

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

. It is used to treat bleeding episodes in people who have acquired hemophilia, among other indications. The most common side effects with Novoseven include venous thromboembolic events (problems caused by blood clots in the veins), rash,

pruritus An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...

(itching),

urticaria Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and typically ...

(hives),

fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

and reduced effectiveness of treatment. The most common side effects with Cevenfacta include injection site discomfort and

hematoma A hematoma, also spelled haematoma, or blood suffusion is a localized bleeding outside of blood vessels, due to either disease or trauma including injury or surgery and may involve blood continuing to seep from broken capillaries. A hematoma is ...

(a collection of blood under the skin) as well as injection-related reactions, an increase in body temperature, dizziness and headache. Novoseven was approved for medical use in the European Union in February 1996, and in the United States in March 1999.

Medical uses

Novoseven is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of bleeding episodes and for the prevention of bleeding in surgical interventions or invasive procedures in people with acquired hemophilia. Novoseven RT is indicated for the treatment of bleeding episodes and peri-operative management in adults and children with

hemophilia A Haemophilia A (or hemophilia A) is a blood clotting disorder caused by a genetic deficiency in clotting factor VIII, thereby resulting in significant susceptibility to bleeding, both internally and externally. This condition occurs almost exclu ...

or B with inhibitors, congenital

factor VII deficiency Factor VII deficiency is a bleeding disorder characterized by a lack in the production of Factor VII (FVII) (proconvertin), a protein that causes blood to clot in the coagulation cascade. After a trauma factor VII initiates the process of coagulati ...

, and

Glanzmann's thrombasthenia Glanzmann's thrombasthenia is an abnormality of the platelets. It is an extremely rare coagulopathy (bleeding disorder due to a blood abnormality), in which the platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/IIIa), which ...

with refractoriness to platelet transfusions, with or without antibodies to platelets and for the treatment of bleeding episodes and peri-operative management in adults with acquired hemophilia. Sevenfact oagulation factor VIIa (recombinant)-jncwis approved for use in the United States and is indicated for the treatment and control of bleeding episodes occurring in adults and adolescents twelve years of age and older with hemophilia A or B with inhibitors (neutralizing antibodies). As of 2012, recombinant factor VIIa is not supported by the evidence for treating most cases of major bleeding. There is a significant risk of

arterial thrombosis Thrombosis () is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fibrin to for ...

with its use and thus, other than in those with factor VII deficiency or acquired hemophilia, it should only be given in clinical trials. Recombinant human factor VII, while initially looking promising in

intracerebral hemorrhage Intracerebral hemorrhage (ICH), also known as hemorrhagic stroke, is a sudden bleeding into Intraparenchymal hemorrhage, the tissues of the brain (i.e. the parenchyma), into its Intraventricular hemorrhage, ventricles, or into both. An ICH is ...

, failed to show benefit following further study and is no longer recommended. In people with hemophilia type A and B who have a deficiency of factors VIII and IX, these two factors are administered for controlling bleeding or as prophylaxis medication before starting surgeries. However, in some cases they subsequently develop neutralizing antibodies, called inhibitors, against the drug. These inhibitors often increase over time and inhibit the action of

coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of co ...

in the body. Recombinant factor VIIa, which is an activated form of factor VII, bypasses factors VIII and IX and causes coagulation without the need for factors VIII and IX. It may be used in acquired hemophilia patients with higher inhibitor titers. Other indications include use for patients with inherited deficiency of factor VII, and people with Glanzmann's thrombasthenia.

Pharmacology

Mechanism of action

This treatment results in activation of the extrinsic pathway of blood

. Recombinant factor VIIa activates factor X, which starts the clotting process and thereby provides control of the bleeding. Because factor VII acts directly on factor X, independently from factors VIII and IX, recombinant factor VIIa can be used to restore haemostasis in their absence or in the presence of inhibitors.

Coagulation factor VIIa (recombinant)-jncw

Coagulation factor VIIa (recombinant)-jncw (Sevenfact) is expressed in the mammary gland of genetically engineered rabbits and secreted into the rabbits' milk. During purification and processing of the milk, FVII is converted into activated FVII (FVIIa). The recombinant DNA (rDNA) construct in the genetically engineered rabbits used for the production of Sevenfact was approved by the FDA's Center for Veterinary Medicine. The safety and efficacy of coagulation factor VIIa (recombinant)-jncw were determined using data from a clinical study that evaluated 27 patients with hemophilia A or B with inhibitors, which included treatment of 465 mild or moderate, and three severe bleeding episodes. The study assessed the efficacy of treatment twelve hours after the initial dose was given. The proportion of mild or moderate bleeding episodes treated successfully both with the lower dose of 75mcg/kg and higher dose of 225 mcg/kg (requiring no further treatment for the bleeding episode, no administration of blood products and no increase in pain beyond 12 hours from initial dose) was approximately 86%. The study also included three severe bleeding episodes that were treated successfully with the higher dose. Another study evaluated the safety and pharmacokinetics of three escalating doses of coagulation factor VIIa (recombinant)-jncw in 15 subjects with severe hemophilia A or B with or without inhibitors. Results from this study were used to select the two doses, 75mcg/kg and 225 mcg/kg, that were evaluated in the study described above. The most common

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of coagulation factor VIIa (recombinant)-jncw are headache, dizziness, infusion site discomfort, infusion related reaction, infusion site hematoma and fever. Coagulation factor VIIa (recombinant)-jncw is contraindicated in those with known allergy or hypersensitivity to rabbits or rabbit proteins. In 2022, the EU approved eptacog beta (Cevenfacta). Both are made by the same manufacturer (LFB) and through rabiit milk. Eptacog beta functions like coagulation factor VII. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

Society and culture

Legal status

Novoseven was approved for use in the United States in March 1999, and indicated for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX. It was approved in October 2006, and indicated for the treatment of bleeding episodes and for the prevention of bleeding in surgical interventions or invasive procedures in patients with acquired hemophilia. Novoseven RT was approved for use in the United States in May 2008 as a room-temperature stable formulation. In January 2010, the label was updated to include a

boxed warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears near the beginning of the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administratio ...

on serious thrombotic adverse events associated with the use of Novoseven RT outside labeled indications. In April 2020, coagulation factor VIIa (recombinant)-jncw (Sevenfact) was approved for use in the United States. In May 2022, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

(CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Cevenfacta, intended for the treatment of bleeding episodes. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. The applicant for this medicinal product is Laboratoire français du Fractionnement et des Biotechnologies (LFB). Eptacog beta (activated) was approved for medical use in the EU in July 2022.

Military use

Recombinant factor VIIa was used routinely in severely wounded American troops during the

Iraq War The Iraq War (), also referred to as the Second Gulf War, was a prolonged conflict in Iraq lasting from 2003 to 2011. It began with 2003 invasion of Iraq, the invasion by a Multi-National Force – Iraq, United States-led coalition, which ...

, credited with saving many lives but also resulting in a high number of deep venous thromboses and pulmonary emboli, as well as unexpected strokes, heart attacks, and deaths.

Research

A possible role in severe postpartum hemorrhage has been suggested.