INTRODUCTION:

Therapies for people with hemophilia (PwH) A (HA) and B (HB) are evolving. While offering significant benefits and addressing unmet needs, long-term monitoring of their safety is essential. To that end, the American Thrombosis and Hemostasis Network (ATHN) captures data from PwH including the use and safety of all available HA and HB therapies through their more than 140 ATHN-affiliated hemophilia treatment centers (HTCs) in the United States (US).

METHODS:

ATHN Transcends (NCT4398628) is a longitudinal, prospective cohort study currently conducted at over 60 ATHN-affiliated sites in the US. The study is approved by central and local institutional review boards. Any person with a diagnosis of congenital HA or HB (factor VIII (FVIII) or IX (FIX) activity <50% and females known to be genetic carriers regardless of their baseline factor activity level) who receive care at a participating site are eligible for inclusion. All participants or their guardians are required to sign informed consent and/or assent prior to participation. Participants are excluded if they have any other known congenital bleeding disorder. Demographic and clinical information are collected at baseline and quarterly. Therapy-related adverse events, including those designated by the European Haemophilia Safety Surveillance group (EUHASS), as well as adverse events of special interest, are recorded and monitored. Health status is measured using the 5-level EuroQol-5D questionnaire (EQ-5D-5L). Descriptive statistics of the baseline medical history and demographic data characterized the enrolled population.

RESULTS:

We obtained consent on the first Hemophilia Natural History Arm's participant in March 2021. As of July 15, 2024, 149 participants (146 male assigned at birth) were enrolled at 17 sites, 121 with HA and 28 with HB. Mean age at enrollment was 20 years (SD: 19.18, range 0 - 86). For those with HA, 83 (68%) had severe, 19 (16%) had moderate, and 19 (16%) had mild FVIII deficiency. For those with HB, 10 (36%) had severe, 13 (46%) had moderate, and 5 (18%) had mild FIX deficiency. Overall, 110 (74%) participants used prophylaxis as their primary therapy, 92 (99%) with severe deficiency. For participants with HA on prophylaxis, 73 (76%) were treated with bispecific antibodies.

The only adverse events reported were upper respiratory infection (URI) (2 participants) and the development of a FVIII inhibitor (after 9 exposure days to FVIII concentrate in one participant on bispecific antibody as primary prophylactic therapy). A single serious adverse event (anemia requiring hospitalization) was reported in a participant with severe hemophilia B on extended half-life factor IX concentrate.

Ninety-eight participants, with a mean age of 28 years (SD: 18.7, range 9 - 86) completed the EQ-5D-5L at baseline. Most (60.2%, n=59) had severe hemophilia, while 21.4% (n=21) and 18.3% (n=18) had moderate and mild deficiencies. Problems with mobility, completing usual activities, and self-care were reported by 21%, 15%, and 7% of these participants. The majory of participants (71.4%) reporting problems with mobility had severe hemophilia. Participants with severe hemophilia also accounted for the majority of those reporting problems with self-care and completing usual activies (71.4%, n=5 and 73.3%, n=11). Problems with pain and anxiety/depression were reported by 34% and 23% of participants at baseline; most had severe hemophilia (69.7%, n=23 and 60.8%, n=14; respectively). The mean health status rating at baseline was 85 out of 100.

DISCUSSION:

The ATHN Transcends Hemophilia Natural History Arm has the capability of enrolling a large cohort of PwH from multiple ATHN-affiliates across the US, monitoring safety events and assessing health status related to living with and being treated for HA and HB. During the first 40 months of data collection of the ATHN Transcends Hemophilia Natural History Arm, we observed no unexpected adverse events associated with contemporary hemophilia therapy. Similar to ATHN 7 (NCT03619863), ATHN's previous hemophilia natural history study, ATHN Transcends Hemophilia Natural History Arm confirms the high prevalence of pain, mobility impairment, and mental health concerns in PwH. Despite advances in therapy, hemophilia continues to significantly impact the lives of PwH.

Disclosures

Corrales-Medina:Bayer: Other: Scientific advisory board, Research Funding; Octapharma: Other: Scientific advisory board, Research Funding; Takeda: Other: Scientific advisory board; Sanofi: Other: Scientific advisory board; CSL Behring: Other: Scientific advisory board; Genentech: Other: Scientific advisory board. Carpenter:Genentech, Inc., Kedrion, Novo Nordisk: Honoraria. Chrisentery-Singleton:Novo Nordisk: Consultancy, Honoraria, Speakers Bureau; takeda: Consultancy, Honoraria, Speakers Bureau; Biomarin: Consultancy, Honoraria, Speakers Bureau; Octapharma: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria, Speakers Bureau; Genentech: Consultancy, Honoraria, Speakers Bureau; hema biologics: Consultancy, Honoraria, Speakers Bureau; kedrion: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Spark: Consultancy, Speakers Bureau. Zia:Star Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; COR2ED GmbH: Membership on an entity's Board of Directors or advisory committees; Hema Biologics: Membership on an entity's Board of Directors or advisory committees. Recht:Bayer: Research Funding; CSL Behring: Ended employment in the past 24 months, Research Funding; Genentech: Consultancy, Research Funding; Grifols: Research Funding; HEMA Biologics: Consultancy, Research Funding; LFB: Research Funding; Novo Nordisk: Consultancy, Research Funding; Octapharma: Research Funding; Pfizer: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Takeda: Research Funding; uniQure: Consultancy, Research Funding; Spark Therapeutics: Research Funding; Partners in Bleeding Disorders: Membership on an entity's Board of Directors or advisory committees.

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2024
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