BACKGROUND:Substantial rates of nonadherence are observed among people with hemophilia A (PwHA) receiving standard- or extended-half-life factor (F)VIII replacement products, although better adherence is associated with fewer bleeding events and better quality of life. Emicizumab is the first bispecific FIXa-/FX-directed antibody approved for routine prophylaxis in PwHA. More real-world adherence and persistence data on emicizumab and other new hemophilia treatments are needed to better inform decisions on population health care and individualized treatments for PwHA. OBJECTIVE:To describe real-world emicizumab adherence and persistence among PwHA in the United States. METHODS:This retrospective, observational cohort study used adjudicated health plan claims data from IQVIA PharMetrics Plus. This study included PwHA with at least 1 claim noting hemophilia A diagnosis between May 1, 2017, and September 30, 2023; at least 2 claims for emicizumab fills between November 1, 2017, and September 30, 2023; and continuous medical and pharmacy insurance benefit coverage for at least 6 months before and at least 12 months after the first emicizumab fill (index date). Adherence to emicizumab was measured during the 12-month post-index period using the proportion of days covered (PDC). Persistence was defined as the proportion of PwHA who did not discontinue emicizumab during the post-index period, where discontinuation was defined as a treatment gap of at least 60 days. Among adherent PwHA (PDC ≥ 80%), the number of post-index claims for FVIII were evaluated. RESULTS:A total of 280 PwHA were included in the study, of whom 98% were male and the mean age was 26 (SD = 16) years. Overall, 76% of PwHA were adherent to and 85% of PwHA were persistent with emicizumab. Rates of adherence and persistence were high across age- and geography-based subgroups, ranging from 61% to 97%. Among PwHA adherent to emicizumab (n = 213), 57% had no post-index claims for FVIII. CONCLUSIONS:In the first year following emicizumab initiation, high adherence and low discontinuation rates were observed among PwHA in a real-world setting.
Abstract Background: Type 1 plasminogen deficiency (PLGD-1) is an ultra-rare autosomal recessive disorder affecting approximately 1.6 individuals per million, characterized by fibrin-rich lesions on mucosal surfaces throughout the body. Involvement of the reproductive tract can lead to complications and diminished quality of life. Intravenous (IV) plasminogen concentrate (plasminogen, human-tvmh; Ryplazim®) is the first and only FDA-approved, targeted replacement therapy for PLGD-1. Methods: This subset analysis evaluated seven female participants (ages 5–42 years) from the pivotal phase 2/3 trial, with five continuing into the long-term study, while two received IV plasminogen concentrate therapy under compassionate use programs. At baseline, reproductive tract lesions were identified in the cervix (n=2), uterus (n=2), both cervix and uterus (n=1), and vagina (n=2). Historical reproductive tract symptoms included cervical pain and bleeding, dysmenorrhea, irregular menses, vaginal bleeding, and infertility. Six participants had lesions in other body systems. Plasma plasminogen activity and antigen pharmacokinetic (PK) profiles were assessed after the first and Week 12 doses and plasminogen trough levels were measured throughout the study. Results: Participants received 6.6 mg/kg IV plasminogen concentrate infusions. Median plasminogen activity was 20% (range: <5–31) before the first dose, increasing to a median trough level of 48% (range: 30–70) after 12 weeks of therapy. Plasminogen activity reached normal physiological levels (≥70%) immediately after the first dose and exceeded the upper limit of normal (>130%) in two participants. The plasminogen activity level remained above 70% for 24 hours in three participants. Similar plasminogen antigen profiles were observed between the women and girls, though higher variability compared to plasminogen activity precluded reliable interpretation of antigen-related PK parameters. Dosing frequencies were individualized from every 2–4 days during the initial 48 weeks, to daily to weekly after 48 weeks in the pivotal trial, and every 1–15 days during the long-term study. Site investigators adjusted the dosing frequency based on clinical response, plasminogen activity trough levels, and availability of drug supply. The participants received a median of 68 months of therapy (range: 42–71). Five participants achieved complete resolution of reproductive tract lesions, with a median time of 2.7 months (range: 1.8–24.5). Lesion improvement was observed at 10.9 months in the participant whose lesion completely resolved at 24.5 months. Two participants did not undergo lesion assessment, one with cervical lesions and one with uterine lesions. Repeated trough sampling demonstrated consistent attainment of target plasminogen activity (baseline + 10% absolute change in plasminogen activity) and no formation of new lesions or recurrence of existing lesions when dosing protocols were followed. Notably, a 33-year-old participant with well-documented infertility due to ligneous uterine adhesions achieved pregnancy and delivered a healthy baby during IV plasminogen concentrate therapy. All participants tolerated therapy well, with no neutralizing antibodies or serious adverse events related to IV plasminogen concentrate therapy. Conclusions: IV plasminogen concentrate therapy demonstrated excellent safety and efficacy in managing reproductive tract lesions in females with PLGD-1. Individualized dosing regimens, informed by PK monitoring, effectively resolved reproductive tract lesions in those assessed. This targeted therapy offers substantial therapeutic benefit to manage reproductive tract PLGD-1 associated lesions, with evidence to support improved quality of life; fertility was restored in one patient. The potential of Ryplazim® to restore PLGD-1 associated infertility in affected females requires further study.
