Long-term Jivi Continues to Safely Prevent Bleeds in Severe Hemophilia A

Long-term treatment with Jivi safely and effectively reduced the number of bleeding episodes in adolescents and adults with severe hemophilia A, according to up to seven years of data from the Phase 2/3 PROTECT VIII trial and its extension study.

The new data confirmed the previous findings from the main study, which showed that long-term therapy with the Bayer medication was effective at preventing bleeds — even when given at extended intervals up to once a week — as well as at treating them.

Notably, patients on prophylactic, or preventive, treatment with Jivi experienced a gradual reduction in bleeding rates over time, regardless of their treatment regimen. The benefits also were found whether or not participants were on preventive or on-demand treatment before entering the main study.

These findings were reported in a study titled “Confirmed long‐term safety and efficacy of prophylactic treatment with BAY 94–9027 in severe hemophilia A: final results of the PROTECT VIII extension study,” published in the journal Haemophilia.

Jivi is a replacement therapy approved in several countries, including the U.S., Canada, and Japan, and in the European Union, for treating bleeds in hemophilia A patients, ages 12 and older. It also is approved in these nations as a preventive measure to avoid spontaneous bleeds, as well as excessive bleeding after surgery, in the same patient population.

Formerly known as BAY94-9027, Jivi works by delivering to patients a lab-made version of clotting factor VIII — the clotting protein that’s missing or defective in hemophilia A.

Of note, Jivi was designed specifically to be more stable and remain in the body for longer than other available replacement therapies for hemophilia A. Thus, in effect, the medication potentially extends the dose intervals and reduces the number of doses needed for effective bleeding prevention.

The international, Phase 2/3 PROTECT VIII study (NCT01580293) evaluated Jivi’s safety and effectiveness at preventing or treating bleeds for 36 weeks (about nine months) in 134 boys and men with severe hemophilia A, ages 12–65.

Participants who were on prior prophylactic treatment were only eligible to receive Jivi as prophylaxis, while those previously receiving on-demand treatment for their bleeds could choose to receive the long-lasting therapy either on-demand or as a preventive treatment.

During the trial, the 114 patients on Jivi prophylaxis received the therapy either twice a week, once every five days, or once every seven days, according to their bleeding rates in an initial 10-week run period. In that period, the participants had been given the treatment twice weekly.

Previous, final data from PROTECT VIII showed that Jivi safely and effectively prevented bleeds with each of the dosing regimens, and resolved 91% of bleeding events with up to two on-demand infusions.

Of the 126 participants completing the trial, 121 chose to enter its extension study, in which all continued treatment — 107 as prophylaxis and 14 as on-demand — for at least 100 days of Jivi infusions. Prophylaxis regimens could vary, depending on individual patients’ needs.

“PROTECT VIII extension has the longest individual patient follow‐up of any other extension studies in adolescents and adults with severe hemophilia A,” the researchers wrote.

Results from both studies showed that, at the end of the extension study, participants had been treated with Jivi for a median of 3.9 years (range of 0.8–7.0 years).

Prophylaxis patients received the therapy for a median of 3.2 years (with a range of 0.1–6.3 years) during the extension study, and at the last visit, 72 of them (67.3%) were on regimens with extended dosing intervals. Such intervals were once every five or seven days.

Compared with the period before entering PROTECT VIII, participants on Jivi prophylaxis experienced a gradual drop in annualized bleeding rates (ABRs) throughout both studies, regardless of therapy regimen and whether they were given on-demand or preventive treatment before enrolling in the main trial.

In turn, an increase in ABRs was observed among patients receiving Jivi to treat bleeding events only.

During the extension study, prophylaxis patients had lower annualized rates of total bleeds (1.49 vs. 34.09), spontaneous bleeds (0.75 vs. 20.74), and joint bleeds (0.88 vs. 20.81) than those using Jivi on demand.

Notably, the number of Jivi infusions received by patients on once-a-week prophylaxis during the extension was close to that given to the participants receiving on-demand treatment. Still, this extended interval-preventive regimen “resulted in marked improvement in ABRs in these patients compared with the on‐demand group,” the researchers wrote.

Jivi was generally well-tolerated during the extension study, with few reports of treatment-related adverse events or side effects (8.3%), most of which were mild in severity. No patient developed antibodies against the delivered FVIII, and no allergic reactions, blood clot-related events, or deaths were reported.

These findings highlighted that “ABR remained low in all prophylaxis groups and was maintained over [at least] 5 years using infusion schedules best fitting individual patients’ needs and low annual FVIII consumption, providing important long‐term efficacy and safety profiles,” the researchers wrote.

“With an established safety profile, long‐acting FVIII replacement therapies, including [Jivi], provide comprehensive management of hemophilia A, allowing patients to meet their lifestyle goals,” the team concluded.