Jivi May Prevent Minor Surgery Bleeds in Severe Hemophilia A Patients

Bayer’s Jivi safely and effectively prevents bleeds during and after minor surgery in children, adolescents, and adults with severe hemophilia A, according to interim data from the Phase 2/3 PROTECT VIII and the Phase 3 PROTECT VIII Kids clinical trials.

Most of the included patients were on prophylactic, or preventive, treatment with Jivi, suggesting that such regimen may be sufficient to prevent bleeding events in patients undergoing minor surgeries, the researchers noted.

Data also showed that undergoing minor surgery on the day of the scheduled treatment infusion was highly effective at preventing the need for additional infusions.

These findings support the use of Jivi before, during, and after minor surgeries in severe hemophilia A patients, and add to the growing body of evidence highlighting the treatment’s effectiveness at reducing bleeds in this patient population.

The results were reported in the study, “Safety and efficacy of BAY 94–9027, an extended‐half‐life factor VIII, during minor surgical procedures in patients with severe hemophilia A,” and published in the form of a letter to the editor in the journal Haemophilia.

Jivi, a replacement therapy formerly known as BAY 94-9027, delivers a lab-made version of clotting factor VIII (FVIII) — the clotting protein that is missing or is defective in hemophilia A — directly to the patients’ bloodstream.

It is approved in several countries, including the U.S., Canada, and Japan, and those in the European Union, for preventing and treating bleeds, including those related to surgery, in hemophilia A patients, ages 12 and older.

Notably, Jivi was designed to be more stable and remain in the body for longer than other available replacement therapies for hemophilia A, potentially reducing the number of doses needed for effective bleeding prevention.

Its greater stability and persistence in the body also is expected to support the body’s natural processes to prevent and stop excessive bleeding due to surgery until wounds are healed.

While Jivi was shown previously to be effective and well-tolerated in severe hemophilia A patients undergoing major surgeries, there is limited data on its effects in minor surgeries, which may be linked to a higher risk of bleeds in this patient population.

“Local hemostasis may not be ensured with suturing, cautery or pressure application, and minor procedures may be performed without the involvement of an experienced multidisciplinary team,” the researchers wrote. Hemostasis is the natural process of slowing blood flow and forming clots at sites of injury to prevent blood loss.

Now, Bayer and researchers involved in Jivi trials evaluated the therapy’s safety and effectiveness in children, adolescents, and adults with severe hemophilia A who underwent minor surgery while participating in the Phase 2/3 PROTECT VIII trial (NCT01580293) and the PROTECT VIII Kids study (NCT01775618).

PROTECT VIII included 134 boys and men, ages 12–65, while PROTECT VIII Kids recruited 73 boys younger than 12. In both studies, patients received the long-lasting therapy, either on-demand or as a preventive treatment. When given as preventive treatment, Jivi was administered twice a week, once every five days, or once every seven days.

The interim analysis included data from 36 adolescents and adults (median age 38.5 years) and five children (median age 4), who underwent a total of 69 minor surgeries (62 in adolescents and adults and seven in children). Data were collected up to Feb. 15, 2017.

Surgeries were classified as minor if: the overall bleeding risk was low; they were not done routinely under general anesthesia in non-hemophilic individuals; they did not require penetration into, or exposure of, a major body cavity; and had no potential to result in substantial physical or physiologic impairment.

Most (65.2%) minor surgeries were dental procedures, followed by orthopedic surgery (10.1%), dermatologic procedures (10.1%), ophthalmologic surgery (5.8%), and others (8.7%).

Most patients (72%) were receiving Jivi as regular prophylaxis every five or seven days, while four patients (9.8%) were treated as needed. Antifibrinolytics, most often tranexamic acid, were used in 17 (24.6%) minor surgeries. Antifibrinolytics are medications to promote blood clotting and used commonly in hemophilia patients undergoing surgical procedures.

Results showed that blood loss was absent (79.7%) or minimal (less than 10 ml; 17.4%) in nearly all surgical procedures, while greater bleeds (of 20 ml and 100 ml) were reported in two cases.

Patients’ hemostasis during all 57 surgeon-rated procedures was classified as “good” (blood loss as expected, 56.1%) or “excellent” (less than expected, 43.9%). In addition, no blood transfusions were needed, and no bleeding complications occurred during and after surgery.

None of the patients developed antibodies against the delivered FVIII either, which can impair treatment effectiveness.

Moreover, 23 (33.3%) minor surgeries, including 14 dental procedures, were performed without additional Jivi infusions. Most (91%) of these surgeries “were performed on the day of patients’ scheduled prophylaxis infusions, at their regular prophylactic dose,” the researchers stated.

In the remaining 46 procedures, dose and frequency of additional Jivi infusions were individualized for each patient, and 80.4% of these procedures were accompanied by a single infusion before, during, or after surgery.

Notably, in 81% of the 26 surgeries performed on the day of the scheduled prophylaxis infusion, the patients did not receive any additional infusions, while additional dosing was required in 93% of the 30 procedures conducted one week after patients’ previous preventive infusion.

These interim findings highlighted that Jivi was generally safe, prevented bleeds, lowered the need for additional infusions in children, adolescents, and adults with severe hemophilia A undergoing minor surgeries.

They also suggest that most patients on Jivi prophylaxis undergoing minor surgeries “can be managed effectively by performing the required procedure under adequate FVIII coverage provided by their regular prophylaxis dosing, or with an additional single infusion during the perioperative period.” (The perioperative period comprises the period immediately before, during, and shortly after surgery.)

In addition, data also showed that “scheduling an operation for a day of the patient’s regular prophylactic infusion may make additional perioperative infusions unnecessary,” the team added.