Bayer announced that the U.S. Food and Drug Administration (FDA) has approved Jivi (antihemophilic factor recombinant, PEGylated-aucl) for use in pediatric patients aged 7 to 12 years with hemophilia A, expanding treatment options for children with this rare bleeding disorder.
The extended approval marks a significant milestone in hemophilia care, as Jivi was previously only approved for adults and adolescents aged 12 years and older since its initial FDA authorization in September 2018. The therapy can be used for on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce bleeding frequency.
"Bayer remains dedicated to meeting the needs of the hemophilia A community," stated Jessica Charlet, Scientific Director at Bayer. "The FDA's approval for pediatric patients 7 to under 12 years of age is reflective of Bayer's commitment to the hemophilia A community and underscores our commitment to supporting families through their treatment journey."
Clinical Evidence Supporting Approval
The FDA's decision was based on data from two key clinical trials: the Alfa-PROTECT study (NCT05147662) and the PROTECT Kids study (NCT01775618), which collectively demonstrated Jivi's safety and efficacy in pediatric patients with severe hemophilia A.
The Alfa-PROTECT study was a multicenter, prospective, single-arm trial that evaluated the safety of Jivi for prophylaxis and treatment of bleeding in previously treated pediatric patients aged 7 to under 12 years. The study specifically assessed the potential risk of hypersensitivity reactions and loss of efficacy associated with an immune response to polyethylene glycol (PEG) during the first four exposure days.
In this trial, 35 patients with a median age of 8 years (range 7-11) received prophylactic treatment with Jivi twice weekly (40-60 IU/kg) for at least 50 exposure days over a 26-week period. Thirty-two patients completed the treatment phase and continued in an 18-month extension study. The study met its objectives, with no unexpected safety concerns and favorable outcomes, including low annualized bleed rates (ABRs).
The PROTECT Kids study further evaluated the pharmacokinetics, safety, and efficacy of Jivi in previously treated pediatric patients under 12 years of age, with the primary efficacy endpoint being the annualized bleed rate. The study successfully demonstrated that Jivi effectively reduced bleeding episodes in this population, with safety findings consistent with the known profile of the therapy.
Hemophilia A: Disease Burden and Diagnosis
Hemophilia A is a genetic bleeding disorder caused by insufficient levels of clotting factor VIII. According to data collected from federally funded hemophilia treatment centers between 2012 and 2018, an estimated 33,000 males in the United States are living with the disorder. Hemophilia A is 3 to 4 times more common than hemophilia B, which results from low levels of clotting factor IX.
Most individuals with hemophilia in the U.S. are diagnosed at an early age. CDC data indicate that the median age at diagnosis is 1 month for severe hemophilia, 8 months for moderate hemophilia, and 36 months for mild hemophilia. Approximately two-thirds of infants diagnosed with hemophilia have a known family history of the condition.
Dosing and Administration Guidelines
For pediatric patients aged 7 to under 12 years, the initial recommended dosing for Jivi is 60 IU/kg twice weekly, with adjustments based on the patient's clinical response and/or recovery. For adults and adolescents, the recommended initial dosage regimen is 30-40 IU/kg twice weekly, with the ability to extend to every five days (45-60 IU/kg) and further individual adjustments based on bleeding episodes.
Important Safety Considerations
Bayer has emphasized that Jivi is not indicated for use in children under 7 years of age due to a higher risk of hypersensitivity reactions and/or loss of efficacy. The therapy is also not approved for previously untreated patients or for the treatment of von Willebrand disease.
The most common adverse reactions (incidence ≥5%) observed in clinical trials included headache, fever, cough, and abdominal pain. Hypersensitivity reactions, including severe allergic reactions, have occurred with Jivi. The therapy may contain trace amounts of mouse and hamster proteins, and patients may develop hypersensitivity to these non-human mammalian proteins.
Additionally, neutralizing antibody (inhibitor) formation has occurred following administration of Jivi, and an immune response associated with IgM anti-PEG antibodies, manifested as symptoms of acute hypersensitivity and/or loss of drug effect, has been reported.
Expanding Treatment Options
This approval represents an important advancement in the management of hemophilia A for younger patients, providing an extended half-life factor VIII option that may help reduce the frequency of infusions while maintaining effective bleeding control.
As treatment options continue to evolve, the expansion of Jivi's indication to include children aged 7 to 12 years offers healthcare providers and families another therapeutic choice in the ongoing effort to improve outcomes and quality of life for pediatric patients with hemophilia A.
