Etranacogene dezaparvovec, the first gene therapy approved for haemophilia B treatment, was shown to be superior to treatment with continuous prophylactic factor IX in terms of bleeding protection 18 ...months after gene therapy in a phase 3 trial. We report post-hoc 24-month efficacy and safety data from this trial to evaluate the longer-term effects of etranacogene dezaparvovec in individuals with haemophilia B.
The phase 3 HOPE-B trial enrolled males aged 18 years or older with inherited haemophilia B, classified as severe (plasma factor IX activity level <1%) or moderately severe (plasma factor IX activity level ≥1% and ≤2%), with a severe bleeding phenotype and who were on stable continuous factor IX prophylaxis. Participants were treated with a single infusion of etranacogene dezaparvovec (2 × 10
genome copies per kg of bodyweight). The primary endpoint, reported previously, was non-inferiority of the annualised bleeding rate (ABR) during the 52 weeks following stable factor IX expression (defined as months 7-18 after treatment) versus an at least 6-month lead-in period in which participants received their usual continuous factor IX prophylaxis, and is updated here up to month 24. Additional, post-hoc efficacy analyses, including adjusted ABR, factor IX activity, participants within factor IX ranges, and factor IX use, and safety analyses were performed at 24 months after gene therapy. Data were analysed in the full analysis set, which comprised the 54 patients who received at least a partial dose of gene therapy. The trial is ongoing and is registered with ClinicalTrials.gov, number NCT03569891.
The study began on June 27, 2018, and participants were treated between January, 2019, and March, 2020; the date of data cutoff was April 21, 2022. 54 adult males (40 White, two Asian, one Black or African American, 11 other or missing) received a single intravenous infusion of etranacogene dezaparvovec and were followed for a median of 26·51 months (IQR 24·54-27·99), after a lead-in period of 7·13 months (6·51-7·82). In the updated analysis comparing months 7-24 after gene therapy to the lead-in period, mean adjusted ABR significantly reduced from 4·18 to 1·51 (p=0·0002) for all bleeds and from 3·65 to 0·99 (p=0·0001) for factor IX-treated bleeds. During each 6-month period after gene therapy, at least 67% of participants experienced no bleeding (36 of 54 during months 0-6 and stable thereafter), compared with 14 (26%) of 54 during the lead-in period. 24 months after gene therapy, 1 (2%) participant had one-stage factor IX activity less than 5%, whereas 18 (33%) had factor IX activity more than 40% (non-haemophilia range), with mean factor IX activity stable and sustained at 36·7% (SD 19·0%). 52 (96%) of 54 participants expressed endogenous factor IX, remaining free of factor IX prophylaxis at month 24. No new safety concerns were identified and no treatment-related serious adverse events or treatment-related deaths occurred. The most common treatment-related adverse events were an increase in alanine aminotransferase (nine 17% of 54 patients), headache (eight 15%), influenza-like illness (seven 13%), and an increase in aspartate aminotransferase (five 9%).
By providing durable disease correction throughout the 24 months after gene therapy, etranacogene dezaparvovec provides a safe and effective therapeutic option for patients with severe or moderately severe haemophilia B.
uniQure and CSL Behring.
Key Clinical Message
We report a case of lung adenocarcinoma‐associated hypercoagulability leading to venous limb gangrene, managed successfully with argatroban and then dabigatran. Use of ...idarucizumab permitted diagnostic investigations, leading to targeted antineoplastic therapy with crizotinib, surgical resection with curative intent, and continued survival over 2 years after the index event.
We report a case of lung adenocarcinoma‐associated hypercoagulability leading to venous limb gangrene, managed successfully with argatroban and then dabigatran. Use of idarucizumab permitted diagnostic investigations, leading to targeted antineoplastic therapy with crizotinib, surgical resection with curative intent, and continued survival over 2 years after the index event.
Research into how people get their health care, called health services research, is important to understand if care is being delivered equitably and efficiently. This research figures out how to ...provide the best care at the lowest cost and finds out if everyone gets equally good care. Diversity and inclusion research focuses on whether all marginalized and minoritized populations (such as a given social standing, race, ethnicity, sex, gender identity, sexuality, age, income, disability status, language, culture, faith, geographic location, or country of birth) receive equitable care. This includes checking whether different populations are all getting the care they need and looking for ways to improve the care. Implementation science studies how to make a potential improvement work in the real world. The improvement could be a new way to diagnose or treat a health condition, a better way to deliver health care or do research, or a strategy to remove barriers preventing specific populations from getting the best available care. The National Hemophilia Foundation focuses on improving the lives of all people with bleeding disorders (BD). They brought BDs doctors, nurses, physical therapists, social workers, professors, and government and industry partners together with people and families living with BDs to discuss research in the areas described above. The group came up with important future research questions to address racism and other biases, and other changes to policies, procedures, and practices to make BD care equitable, efficient, and effective.
The National Hemophilia Foundation (NHF) conducted extensive all-stakeholder inherited bleeding disorder (BD) community consultations to inform a blueprint for future research. Sustaining and expanding the specialized and comprehensive Hemophilia Treatment Center care model, to better serve all people with inherited BDs (PWIBD), and increasing equitable access to optimal health emerged as top priorities.
NHF, with the American Thrombosis and Hemostasis Network (ATHN), convened multidisciplinary expert working groups (WG) to distill priority research initiatives from consultation findings. WG5 was charged with prioritizing health services research (HSR); diversity, equity, and inclusion (DEI); and implementation science (IS) research initiatives to advance community-identified priorities.
WG5 identified multiple priority research themes and initiatives essential to capitalizing on this potential. Formative studies using qualitative and mixed methods approaches should be conducted to characterize issues and meaningfully investigate interventions. Investment in HSR, DEI and IS education, training, and workforce development are vital.
An enormous amount of work is required in the areas of HSR, DEI, and IS, which have received inadequate attention in inherited BDs. This research has great potential to evolve the experiences of PWIBD, deliver transformational community-based care, and advance health equity.
Background
Over 6000 people are on the United Kingdom organ transplant waiting list, and approximately three people die each day due to a lack of donors. Social deprivation status has been shown to ...affect registration. The aim of this study was to evaluate the effectiveness of school level education at increasing awareness of the issues surrounding organ donation and organ donor registration, and the effect of socioeconomic deprivation and age has on these outcomes.
Methods
A 15‐minute presentation about organ donation and the issues in transplantation was given to secondary school students from the United Kingdom. An optional questionnaire was then distributed.
Results
1155 paper questionnaires were completed from nine schools. The average age was 15.5 (SD = 0.5) years. Before the presentation, 10% of students were on the ODR. Following the presentation, the number of students who were on the ODR or planned to join significantly increased to 56%, independent of age (P < 0.0001). Similarly, there was a significant increase in Likert scores for awareness of the issues in transplantation, independent of age (P < 0.0001).
Conclusions
This early educational presentation significantly increased awareness of the issues in transplantation and planned organ donor registration, independent of age and deprivation.
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