Less frequent infusions with Jivi led to fewer bleedings, a greater ability to engage in physical and workplace activities, less vein damage, and better emotional well-being in men with severe hemophilia A compared to previous therapies used, participants in a Phase 2/3 trial largely agreed.
“Exploring the Impact of Infusion Frequency in Hemophilia A: Exit Interviews with Patients Participating in BAY 94-9027 Extension Studies (PROTECT VIII)” appeared in the journal The Patient – Patient-Centered Outcomes Research.
Treating severe hemophilia A with extended half-life replacement therapies allows for longer times between prophylactic (preventive) infusions while still showing efficacy and safety. These therapies may improve treatment adherence, clinical outcomes, and quality of life.
Bayer’s Jivi (previously BAY 94-9027) is an FDA approved preventive or on-demand therapy for hemophilia A patients ages 12 and older. It has shown extended half-life — the time required to reduce the amount of a compound by half and an indicator of how long its benefits last — compared to standard factor VIII (FVIII) replacement schedules in Phase 1 (NCT01184820) and Phase 2/3 trials (NCT01580293; called PROTECT VIII). FVIII is the clotting protein missing or defective in people with hemophilia A.
Still, direct patient experiences with long-term use of such products is not well-known. “Exit interviews” have been recommended by both regulatory and research communities to promote patient-centered assessments of treatment benefits. They are especially valuable in the context of newer therapies and rare diseases, where information on patient-reported outcome measures in clinical trials may be limited.
A team from Bayer and Adelphi Values used such interviews to gather patients’ perspectives on Jivi and its reduced infusion frequency.
Sixteen men (mean age, 46.6), all participants in the PROTECT VIII 36-week extension study testing Jivi for on-demand and prophylaxis treatment in patients with no history of inhibitors, volunteered. They lived in Israel, The Netherlands, and the U.S.
Most of these men (11) were on an infusion schedule of once every five days, while three others used Jivi once every seven days, and the remaining two were on twice a week regimen.
Interviews were conducted via telephone and lasted 30 minutes. Discussions were initially broad, then turned specific to assess satisfaction with current and prior therapies, as well as perspectives on infusion frequency, factor coverage, and health-related quality of life.
Twelve patients considered infusion frequency to be among the most important aspects of a treatment for hemophilia A, with one patient citing longer-lasting blood coagulation as the most relevant factor.
Other key attributes included safety, including risk of adverse effects (six patients); mode of administration (six); convenience of preparation (four); and quantity of product needed (two).
Fourteen of the 16 put emphasis on the longer time Jivi stays in the body relative to other replacement therapies used, with 15 mentioning that this allowed less frequent infusions, and nine saying that the treatment led to more stable FVIII blood levels over the week.
“The previous one was a maximum of 48 h. This one is good for 5–7 days. You feel that you are still in relatively good shape even if you don’t inject on the fifth day,” one patient was reported to respond.
Importantly, 14 men also said they had less frequent bleeds with Jivi than with other therapies. The two other participants — both on an E7D schedule — indicated no change here.
As for the treatment’s impact on daily and physical activities, nine patients in total reported being more active or less restricted in their general physical activity (five men), walking/hiking (four), and swimming, taking stairs, playing golf, and going to the gym (one for each listed). Three men mentioned as a key improvement a lesser worry or fear of developing bleeds.
“Listen, I walk. I go down stairs. I’m not afraid of having a bleed. The factor lasts in my body,” one patient said.
Intravenous delivery of FVIII can lead to complications such as vein damage and/or scarring, a need to heal after each injection, and swelling at the injection site. Fewer weekly infusions, for this reason, led to most patients reporting lesser long-term damage, while three added that the longer intervals between infusions enabled better healing.
Five of eight patients said the infusions had become part of their routine and/or did not represent a scheduling problem, though they could be time-consuming. Nine thought Jivi’s scheduling and administration time better than previous therapies, and four others had no issues with prior regimens and did not see lesser administration time as an added benefit.
Six participants mentioned an impact on work, including greater confidence, fewer or no absences, and greater productivity. Twelve reported benefits in emotional and psychological well-being following treatment with Jivi, such as more confidence (seven patients), less worrying (four) and fear (two), or not needing to think about hemophilia and/or treatment (four).
Six men discussed why they were unable to adhere to infusion schedules with previous therapies. Among reasons they mentioned were forgetting and intentionally avoiding such infusions. One patient talked about how less frequent treatment with Jivi means better adherence and overall health.
“[It] is not too often and it is a big advantage for me. Before I used the current treatment, I had bleedings regularly,” he said. “And now when I use this, like I said, I have those two, three, four times a year so at most. That is a big improvement for me.”
“Findings from the present study serve to further highlight the value of treatments with reduced infusion frequency to patients with hemophilia,” the scientists wrote. “Such data could be of value to a range of stakeholders … and facilitate patient–clinician discussions to promote tailored treatment decisions.”