Jivi was safe and effective at preventing and treating bleeds for more than five years in boys under age 12 with severe hemophilia A, according to long-term data from a Phase 3 trial’s extension study.
Data analysis also showed that most of these children stayed with the treatment as they turned adolescents.
The study based on these findings, “PROTECT VIII kids extension study: Long-term safety and efficacy of BAY 94-9027 (damoctocog alfa pegol) in children with severe haemophilia A,” was published in the journal Haemophilia.
Replacement of coagulation factor VIII (FVIII), the blood clotting protein missing in people with hemophilia A, is currently the standard treatment for the disorder. But some replacement therapies require patients to receive regular injections (possibly three each week), affecting their quality of life and posing a challenge to effective, continuous treatment.
Formerly known as BAY 94-9027, Jivi is an extended half-life FVIII replacement therapy developed by Bayer, and currently approved in the U.S. and in the EU as a prophylactic, or preventive, treatment for hemophilia A in patients ages 12 and older.
Jivi is administered as an infusion directly into the bloodstream, and can also be used as an on-demand treatment for bleeds. Importantly, Jivi stays in the patients’ blood longer than some standard therapies, reducing the number of infusions needed to maintain FVIII levels within a normal range.
The Phase 3 PROTECT VIII Kids trial (NCT01775618) and its subsequent 12-week extension study found Jivi to be safe and effective at preventing and treating bleeds in boys under the age of 12 with severe hemophilia A.
In the main study, patients were randomized to Jivi infusions twice weekly at a dose ranging between 25–60 international units (IU)/kg, every five days at a dose of 45–60 IU/kg, or every seven days at a dose of 60 IU/kg. All were treated for at least 50 exposure days, and divided into younger (ages 6 and younger) and older (ages 6–12) patient groups.
Children ages 6 and younger who completed the main trial were given the option to enroll in a safety expansion study, where they continued to receive twice-weekly infusions of Jivi at a dose ranging between 25–60 IU/kg for 12 weeks.
All patients finishing either the main trial or the safety expansion study were also given the option of joining an extension trial assessing Jivi’s long-term safety and efficacy at their same dosing regimens and schedules. (At the investigating doctor’s recommendation, dosing regimens could change.)
Of the 61 patients who completed the main and expansion trials, 59 (97%) enrolled in the optional extension study. Of these, 32 patients were in the younger age group and 27 in the older age group. The median age of the younger patients was 3.5 at trial enrollment and 9 at the extension study’s conclusion, while the median age of the older patients was 9 at enrollment and 15 at the conclusion.
Of these 59 patients, 57 (97%) completed the extension study, which ran for a median of five years. Two boys under the age of 6 left for reasons unrelated to the treatment.
A total of 58 patients (98.3%) had 100 or more total exposure days throughout the study.
The median total number of infusions each year was 77.5, and treatment compliance was greater than 95% across all patients and dosing regimens, the study reported.
At the start of the extension, a majority of patients (27) were being treated every five days. At its end, most (29) were on the twice-weekly treatment schedule.
The median annualized bleeding rate (ABR), which measures the annual number of bleeds, was 1.6 in all patients — 1.5 in younger patients, and 1.9 in older boys — indicating that Jivi was effective at controlling bleeds in these patients. Notably, during the last year of treatment, the median spontaneous ABR was zero across all patients.
Patients reported a total of 667 bleeds (323 in younger patients and 344 in older ones) during the extension study. Most bleeds were mild (41.6%) or moderate (47.7%), with the majority (75%) being trauma-related. Most bleeds required no more than two infusions, with good or excellent treatment response in 87.4% of all cases.
Adverse effects were reported by 56 patients (95%) during the extension study. Most were either mild (20.3%) or moderate (61%), while 13.6% were considered severe. Serious adverse events were reported in 20 patients, 13 in younger patients and seven in older patients.
No adverse events “of special interest …. defined as loss of efficacy or hypersensitivity reactions, were reported during the extension study,” the researchers wrote.
Based on these findings, “BAY 94‐9027 showed long‐term safety and efficacy for the prevention and treatment of bleeds in younger and older paediatric patients with severe haemophilia A,” they concluded.
Data also demonstrated that “most children who started BAY 94-9027 prophylaxis when aged [under] 12 years continued treatment into adolescence with sustained safety and efficacy.”
Three of this study’s nine researchers are employees of Bayer, which also funded the work.
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