Kovaltry (octocog alfa, previously known as BAY 81-8973) is a recombinant antihemophilic factor therapy approved to manage the symptoms of hemophilia A in adults and children. It is developed and marketed by Bayer.

How Kovaltry works

Hemophilia A is an inherited condition caused by a mutation in coagulation factor VIII, or F8 gene. Factor VIII is a clotting factor, a protein that is essential for normal blood clotting and to control bleeding. A deficiency in this protein causes the patient to bleed excessively. This can include bleeding into joints, muscles, and organs, which can lead to permanent damage.

The active substance is octocog alfa, a protein engineered to be identical to the full-length natural factor VIII found in the body. This is the same active substance in Bayer’s Kogenate, but is produced using different manufacturing techniques.

Kovaltry is produced using cells from a baby hamster kidney cell line that have been provided with the gene for octocog alfa, along with the human chaperone protein heat shock protein 70 (HSP70). The cells produce the octocog alfa protein, and the HSP70 protein ensures it is correctly folded to work as a functioning protein. The addition of HSP70 in the manufacturing process is unique to Kovaltry.

No additional human or animal derivatives are used in the manufacturing process, and Kovaltry is purified in a multistep process, including a dedicated step to remove any viruses.

Kovaltry aims to temporarily replace the deficient factor VIII protein in the body. This allows for normal blood clotting to occur while Kovaltry is present in the blood, allowing the patient to have temporary control of bleeding.

Kovaltry in clinical trials

On Feb. 22, 2016, the European Commission granted Bayer approval to market Kovaltry in Europe. This was followed a month later by approval from the U.S. Food and Drug Administration on March 17, 2016.

The regulatory approvals were based on the LEOPOLD clinical trials, including LEOPOLD 1 (NCT01029340), LEOPOLD 2 (NCT01233258), and LEOPOLD Kids (NCT01311648).

The Phase 3 LEOPOLD 1 trial assessed the safety and efficacy over a one-year period in 62 men with severe hemophilia A. The patients were randomly assigned a dose between 20 to 50 IU per kg body weight to be taken two or three times a week. The results, published in the journal Haemophilia, confirmed that Kovaltry was safe and significantly reduced the median number of bleeds per year.

The Phase 3 LEOPOLD 2 trial compared Kovaltry on-demand to Kovaltry as a prophylaxis therapy. The results, published in the Journal of Thrombosis and Haemostasis, demonstrated that prophylaxis treatment was significantly more effective than on-demand treatment. Prophylaxis treatment reduced the median annualized bleed rate by 97 percent compared to on-demand treatment.

The Phase 3 LEOPOLD Kids trial, which is still ongoing, aimed to evaluate the safety and efficacy of prophylaxis with Kovaltry in children with hemophilia A. Results for 51 patients, ages 1 to 11, treated between June 2011 and January 2013, have been published in the journal Haemophilia. Kovaltry was well tolerated and significantly reduced the median annualized number of bleeds.

The safety and efficacy of Kovaltry during surgery was also assessed as part of the LEOPOLD trials. A total of 32 patients (both adult and child) underwent surgery while receiving Kovaltry, and overall the patients did not experience blood loss outside the expected range for surgery. The results, published in the journal Haemophilia, demonstrate that Kovaltry can successfully control bleeding during surgery.

Other information

It is administered as an intravenous injection. The level and frequency of dosage depends on the patient and should be discussed with a healthcare professional. With long-term use, the body may develop a resistance to Kovaltry, which can prevent it from working. Blood tests are recommended to monitor for antibodies, or “inhibitors.”

Common side effects of Kovaltry include headaches, fever, and rashes. Allergic reactions are possible, especially if the patient is allergic to rodents, such as hamsters. In case of allergic reaction, such as tightness of the chest and throat, dizziness, decrease in blood pressure or nausea, the treatment should be stopped immediately and a healthcare professional should be contacted.

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