NovoSeven for Hemophilia

Last updated Sept. 16, 2022 by Lindsey Shapiro, PhD

✅ Fact-checked by Joana Carvalho, PhD


What is NovoSeven for hemophilia?

NovoSeven (eptacog alfa [activated]) is an approved medication used to treat and prevent bleeding episodes in adults and children with hemophilia.

It was developed and marketed by Novo Nordisk, and is now sold in a formulation designed to be more stable at room-temperature, called NovoSeven RT.

How does NovoSeven work?

Hemophilia is caused by the loss of certain proteins involved in blood clotting, which lead to episodes of uncontrolled bleeding.

After a blood vessel injury, one of these clotting factors, called factor VIIa (FVIIa), is normally activated and kicks off a chain of reactions that ultimately produce fibrin — the protein that sticks together at the site of injury and forms a clot.

NovoSeven is a lab-made form of FVIIa that is similar to the one naturally produced in the body. When infused into the bloodstream during a bleeding episode, NovoSeven stimulates the body’s natural blood clotting cascade.

Who can take NovoSeven?

NovoSeven was first approved by the U.S. Food and Drug Administration (FDA) in 1999 for the treatment and prevention of bleeding episodes in adults and children with hemophilia A or B with inhibitors — neutralizing antibodies against clotting factors. In 2006, the approval was expanded to include adults with acquired hemophilia.

The therapy also is approved for individuals with congenital FVII deficiency and Glanzmann’s  thrombasthenia that is unresponsive to platelet transfusions.

Who should not take NovoSeven?

There are no contraindications for NovoSeven’s use.

How is NovoSeven administered?

NovoSeven comes as a white powder in single-dose vials containing 1,2,5 or 8 mg of recombinant FVIIa and a separate solvent. Before use, the powder is dissolved in the solvent at room temperature to produce a clear, colorless solution at a concentration of 1 mg NovoSeven per 1 mL of liquid.

The solution is administered via an into-the-vein (intravenous) injection, which must be given within three hours of reconstitution. NovoSeven is usually given by healthcare professionals with appropriate experience. In some cases, patients or caregivers may be able to administer NovoSeven after receiving appropriate training.

During an acute bleeding episode, NovoSeven should be administered at the following dose until bleeding stops:

  • Hemophilia A or B with inhibitors: 90 micrograms per kilogram of body weight (mcg/kg) every two hours. For severe bleeds, continue administration every three to six hours after bleeding stops.
  • Acquired hemophilia: 70–90 mcg/kg every two to three hours.

For managing bleeds during surgery, NovoSeven should be administered at the following dose:

  • Hemophilia A or B with inhibitors: 90 mcg/kg immediately before surgery and every two hours during surgery. After a minor surgery, the medication should also be given every two hours for two days, then every two to six hours until healing occurs. After a major surgery, it should be administered every two hours for five days, then every four hours or via continuous infusion at a rate of 50 mcg/kg per hour until healing occurs.
  • Acquired hemophilia: 70–90 mcg/kg immediately before surgery and every two to three hours for the duration of surgery and until bleeding stops.

The doses and frequency of administration may be adjusted by a healthcare provider based on bleeding severity.

NovoSeven in clinical trials

Many clinical trials have been conducted since the 1990s that have established the safety and efficacy of NovoSeven at various doses in adults and children. Trial also were conducted for diverse applications of the therapy, including surgical management.

Trials for hemophilia A and B with inhibitors

A double-blind randomized trial, conducted in the late 1990s, compared two doses of NovoSeven — 35 mcg/kg or 70 mcg/kg — for the treatment of bleeding events in hemophilia patients. That study involved 78 people with hemophilia A and B, both with and without inhibitors. Neither participants nor researchers knew which patients were given which dose.

Patients received an initial NovoSeven infusion at a treatment center within 4–18 hours after a bleed began, which was repeated every 2.5 to four hours. The effects of treatment were evaluated after 12 hours or when treatment stopped, whichever occurred first.

The effects of the 35 mcg/kg dose were deemed excellent in 59% of the cases and effective in 12%. The 70 mcg/kg dose was found to be excellent in 60% of the cases and effective in 11%. The average number of injections needed to stop bleeding was 2.8 for the 35 mcg/kg dose, and 3.2 for the 70 mcg/kg dose.

Two additional clinical trials were conducted to evaluate NovoSeven’s safety and efficacy during or after surgery in hemophilia A or B patients with inhibitors.

One trial evaluated two doses of NovoSeven — this time at 35 mcg/kg or 90 mcg/kg — in 29 patients undergoing major or minor surgical procedures. Participants received their assigned dose once prior to surgery, during surgery as needed, and every two hours for two days after surgery. Additional doses were administered every 2–6 hours for an additional three days, as needed.

This study also was randomized and double-blind, with the participants and researchers not knowing the doses any patients received.

Results showed that bleeding was controlled during surgery in 28 patients. Five days after surgery, bleeding control was deemed satisfactory in all 14 patients treated with 90 mcg/kg and in 11 of the 15 treated with 35 mcg/kg.

A second open-label trial compared the safety and efficacy of a single dose of NovoSeven versus a continuous infusion in 24 patients undergoing major surgery. Because this trial was open-label, the participants and researchers knew which patients were receiving each dose.

The results showed that the two approaches had comparable efficacy in achieving and maintaining bleeding control through 10 days.

Trials for acquired hemophilia

Data supporting NovoSeven’s use in acquired hemophilia came from four studies collected through a compassionate use program. The studies were conducted by Novo Nordisk or the Hemophilia and Thrombosis Research Society (HTRS) registry.

The analyses overall included 70 patients and 113 bleeding episodes, surgeries, or traumatic injuries. Doses of NovoSeven ranged from 31 to 197 mcg/kg, with a mean dose of 90 mcg/kg and a mean number of injections of six per day. The overall efficacy across all patients was 78%.

Common side effects of NovoSeven

The most common side effects experienced by patients using NovoSeven include:

  • Blood clots, or thrombotic events.

Blood clots

Serious blood clotting events have been reported in patients treated with NovoSeven. Patients using other clotting medications, older individuals, and those with a history of cardiovascular disease may be at an increased risk of blood clots.

All patients should discuss with their healthcare providers the signs and symptoms associated with thrombotic events prior to receiving NovoSeven, and should be monitored for blood clot development. If a blood clot event occurs, the dose of NovoSeven should be lowered or stopped at the healthcare provider’s discretion.

Allergic reactions

Allergic reactions, including airway closure (anaphylaxis) can occur with NovoSeven. Patients with a known sensitivity to mouse, hamster, or cow proteins may be at a higher risk of experiencing allergic reactions. NovoSeven should be discontinued if an allergic reaction occurs.

Use in pregnancy and breastfeeding

There are no well-controlled studies evaluating the use of NovoSeven in pregnant women or during breastfeeding, but the therapy was associated with some mortality in animal reproductive studies. No evidence of harm to the developing fetus was observed.

Patient who are pregnant or wish to become pregnant, or breastfeed while using NovoSeven should discuss this with their healthcare provider.

 


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