Last updated Jan. 25, 2023, by Teresa Carvalho, MS
✅ Fact-checked by Joana Carvalho, PhD
What is Kovaltry for hemophilia?
The therapy, previously known as BAY 81-8973, was developed and is now being marketed by Bayer.
How does Kovaltry work?
Hemophilia A is an inherited bleeding disorder caused by a mutation in the F8 gene, which provides instructions for making a blood clotting protein called factor VIII (FVIII). A deficiency in this protein causes patients to bleed excessively, sometimes for no apparent reason.
Octocog alfa, Kovaltry’s active substance, is a protein engineered to be identical to the natural FVIII found in the body. This is the same active substance used in Bayer’s Kogenate, a now discontinued treatment for hemophilia A, but produced for this indication using different manufacturing techniques.
Kovaltry is produced using cells from a baby hamster kidney cell line along with the human chaperone protein heat shock protein 70 (HSP70). The hamster kidney cell line was provided with the gene for octocog alfa. These cells produce the octocog alfa protein, and the HSP70 protein ensures it is correctly folded to work as a functioning protein.
No additional human or animal derivatives are used in the manufacturing process, and Kovaltry is purified in a multistep process. That purification includes a dedicated step to remove any viruses.
By replacing the natural FVIII hemophilia A patients are missing, Kovaltry is expected to restore normal blood clotting.
Who can take Kovaltry?
Both the European Commission and the U.S. Food and Drug Administration granted Bayer approvals in 2016 to market Kovaltry in Europe and the U.S., respectively.
The medication is indicated for the treatment and control of bleeds in adults and children with hemophilia A, as well as to manage excessive bleeding during surgery. It also may be used as a routine preventive treatment (prophylaxis) to lower bleed frequency.
Who should not take Kovaltry?
Kovaltry should not be used by patients who have allergic reactions, including severe and potentially life-threatening reactions to:
- mouse or hamster proteins
- the therapy’s active ingredient or other constituents, such as glycine, sucrose, sodium chloride, calcium chloride, histidine, and/or polysorbate 80.
The therapy is not indicated for the treatment of von Willebrand disease, another inherited bleeding disorder.
How is Kovaltry administered?
Kovaltry is given as an intravenous (into-the-vein) injection. It is supplied as a dry powder in single-use vials containing 250, 500, 1,000, 2,000, or 3,000 international units (IU).
For on-demand treatment and bleed management before, during, and after surgery, the level and frequency of dosage depends on the patient and should be discussed with a healthcare professional.
For routine prophylaxis in adults and adolescents, Kovaltry should be administered at a dose of 20 to 40 IU per kilogram of body weight two or three times weekly. For children ages 12 or younger, the recommended dose is 25 to 50 IU/kg two or three times weekly, or every other day.
For on-demand treatment, Kovaltry is recommended to be given to maintain FVIII activity levels at:
- 20 to 40 IU/dL, with dosing every 12–24 hours for at least one day until healing is achieved, in the case of minor bleeds.
- 30 to 60 IU/dL, with dosing every 12–24 hours for 3–4 days until healing is achieved, in the case of moderate bleeds.
- 60 to 100 IU/dL, with dosing every 8–24 hours until healing is achieved, in the case of major bleeds.
For minor surgical procedures, Kovaltry should be given every 24 hours for at least one day after surgery to maintain FVIII activity levels. The dose should be 30 to 60 IU/dL until healing is achieved.
For major surgical procedures, Kovaltry should be given every 8–24 hours after surgery, at 80 to 100 IU/dL, to maintain FVIII activity levels until healing is achieved. The therapy then should be given for at least seven more days to maintain FVIII activity levels. That dose should be 30 to 60 IU/dL.
Kovaltry should be reconstituted (diluted) before being administered with the components provided with its package.
After reconstitution, Kovaltry should be injected as soon as possible. If not used immediately, the treatment should be stored at room temperature for up to three hours. Injection usually takes from 1–15 minutes and the rate of administration should be adapted to each patient’s response.
Kovaltry in clinical trials
LEOPOLD 1 trial
LEOPOLD 1 assessed the safety and efficacy of Kovaltry over a one-year period in 62 men with severe hemophilia A. Patients were randomly assigned a dose between 20 to 50 IU/kg, to be taken two or three times a week. Results confirmed that Kovaltry was safe and effective at preventing and treating bleeds.
LEOPOLD 2 trial
The goal of LEOPOLD 2, which involved 80 patients with severe hemophilia A, was to compare Kovaltry as an on-demand versus a preventive treatment. The study’s results demonstrated that prophylactic therapy was significantly more effective than on-demand treatment. Prophylaxis reduced the median annualized bleed rate by 97% compared with on-demand treatment.
LEOPOLD Kids trial
As its name suggests, the LEOPOLD Kids trial sought to evaluate the safety and efficacy of Kovaltry as a prophylactic treatment in children with hemophilia A. Involving 51 patients, ages 1–11, this trial showed that Kovaltry was well-tolerated and effective at treating and preventing bleeds.
The safety and efficacy of Kovaltry during surgery also were assessed as part of the LEOPOLD trials. A total of 41 patients — both adults and children — underwent surgery while receiving Kovaltry. The patients, overall, did not experience blood loss outside the expected range for surgery. Accordingly, these results demonstrated that Kovaltry can successfully control bleeding during surgery.
Bayer is sponsoring an observational study (NCT02941783) in hemophilia A patients to collect post-marketing data on the safety and efficacy of Kovaltry in a routine clinical practice setting over a two-year period. The primary goals include assessing the number of participants experiencing side effects as a measure of treatment safety and tolerability. One secondary goal is assessing the number of annual bleeds.
The trial, with an overall enrollment of 231 children and adults with hemophilia A, is estimated to be completed in March 2024.
Common side effects of Kovaltry
The most common side effects associated with Kovaltry include:
Patients may develop allergic reactions, including life-threatening ones known as anaphylaxis, to Kovaltry. The treatment is contraindicated, or not recommended, in patients who have developed allergies to the treatment’s active substance, mouse or hamster proteins, or its other ingredients.
If patients experience symptoms of an allergic reaction, such as chest tightness, dizziness, low blood pressure, or nausea, Kovaltry should be stopped immediately and a healthcare professional contacted.
Development of inhibitors
With long-term use, patients may develop neutralizing antibodies, or “inhibitors” against Kovaltry, which can lower its effectiveness.
This side effect occurs mainly in patients who have not been previously treated or received a correct dose. Monitoring should be done to check for the possible development of inhibitors. Patients should talk with their healthcare team immediately if bleeding does not stop after treatment.
Injection site reactions
Infections at the injection site may occur when Kovaltry is given through central venous catheters. These infections are usually not related to the treatment itself.
Use in pregnancy and breastfeeding
It is unknown if Kovaltry can affect a developing fetus during pregnancy or be passed on to a nursing infant through breast milk. Patients who are pregnant, plan to become pregnant, or are breastfeeding or plan breastfeed should talk with their healthcare team about using this treatment.
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