Adult lifetime cost of hemophilia B management in the US: payer and societal perspectives from a decision analytic model

Li, Nanxin; Maruszczyk, Konrad; Guzauskas, Gregory F.; Slomka, M.; Burke, Tom; Martin, Antony; O’Hara, Jamie; Stevenson, Matt; Recht, Michael

doi:10.1080/13696998.2021.1891088

Cited by 10 publications

(3 citation statements)

References 41 publications

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“…The treatment of affected individuals involves the prophylactic replacement of the missing factor, which reduces the incidence of spontaneous bleeding events and resultant joint damage [ 4 , 5 ]. Replacement therapy has improved life expectancy and quality of life of people with haemophilia (PwH), though limitations such as high costs and the treatment burden of frequent intravenous infusions remain [ 6 , 7 ]. The latter has decreased with the development of extended half-life factor replacement products and factor VIII (FVIII) mimetics [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

The experiences of people with haemophilia and their families of gene therapy in a clinical trial setting: regaining control, the Exigency study

Fletcher

Jenner²,

Pembroke³

et al. 2022

Orphanet J Rare Dis

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Background Gene therapy has the potential to change the life experience of people with haemophilia and family members. Few studies have sought to explore the impact of gene therapy on both individuals and families. The aim of this study was to capture real-life experiences of gene therapy in People with haemophilia and their families. Results Sixteen participants with severe haemophilia (11 haemophilia A, five haemophilia B), mean age 41.4 years (range 23–75 years), took part in a single qualitative interview; ten were accompanied by a family member. Mean time since transfection was 3.56 years (range 1–10 years). Participants saw their involvement in gene therapy as a positive experience, freeing them from the personal burden of haemophilia and furthering treatment options for the wider haemophilia community. However, participants reported being unprepared for the side effects of immunosuppression. Some also reported feeling unsupported and having little control over what was happening as their factor levels became the focus of the process. Conclusion The results suggest that strategies need to be put into place to enable PwH fully to understand the process of gene therapy, and thereby make an informed choice as to whether it is a treatment they might wish for themselves. These include early and ongoing education, increased provision of psychosocial support and ongoing qualitative research.

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Section: Introductionmentioning

confidence: 99%

The experiences of people with haemophilia and their families of gene therapy in a clinical trial setting: regaining control, the Exigency study

Fletcher

Jenner²,

Pembroke³

et al. 2022

Orphanet J Rare Dis

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“…In addition to clinical outcomes, economic burden is a key aspect of hemophilia B treatment. 16 There are no head-to-head trials directly comparing clinical outcomes in rFIXFc-and N9-GP-treated patients. Also, there are no studies with the same reference arms, precluding indirect comparison through a common comparator.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of rFIXFc versus N9-GP Prophylaxis in Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PARADIGM 2 Trials

Mancuso¹,

Eriksson²,

Falk³

et al. 2023

JBM

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Purpose For patients with hemophilia B, extended half-life factor IX (FIX) products are available for prophylaxis and for treating bleeds. Different methods are used to extend the half-lives of recombinant FIX Fc fusion protein (rFIXFc) and nonacog beta pegol (N9-GP). This affects their biodistribution and plasma FIX levels, although differences do not always correlate with clinical outcomes. A matching-adjusted indirect comparison (MAIC) of prophylaxis with rFIXFc and N9-GP was performed, based on licensed dosing in the European Union. Patients and Methods Combined rFIXFc data from the weekly and individualized interval prophylaxis arms of the B-LONG clinical trial, and N9-GP data from the 40 IU/kg once-weekly prophylaxis arm of PARADIGM 2 were used in a MAIC. Individual patient data for rFIXFc (n=87) were matched to aggregated data for N9-GP (n=29). Estimated annualized bleeding rates (ABRs) for rFIXFc were recalculated using a Poisson regression model with adjustment for over-dispersion, and compared with ABRs reported for N9-GP, using incidence rate ratios (IRRs) with 95% confidence interval (CI). Results There was no evidence of significant differences in estimated ABRs between prophylaxis with rFIXFc and N9-GP. Analysis of pooled rFIXFc weekly and interval-adjusted dosing compared with N9-GP 40 IU/kg once weekly produced estimated ABRs of 2.59 versus 2.51 (IRR 1.03; 95% CI 0.56–1.89), as well as 1.34 versus 1.22 (IRR 1.10; 95% CI 0.42–2.91) and 1.13 versus 1.29 (IRR 0.88; 95% CI 0.47–1.63) for overall, spontaneous, and traumatic bleeding events, respectively. Conclusion The study did not reveal any significant differences in the efficacy of rFIXFc and N9-GP prophylaxis. Given differences in trough levels (rFIXFc dosing was targeted to achieve a trough 1–3 IU/dL above baseline versus a reported estimated N9-GP mean trough of 27.3 IU/dL), interpreting plasma FIX levels as potential surrogate efficacy markers requires consideration of compound-specific pharmacokinetic profiles.

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“… 1 Prophylaxis effectively reduces bleeding and ameliorates the bleeding phenotype, but it is associated with substantial treatment burden as well as cost over time. 4 Subcutaneous FIX replacement 5 and rebalancing therapies 6 – 8 are under investigation. Regardless of prophylaxis type, patients still need factor replacement for breakthrough bleeds, trauma, and surgery.…”

Section: Introductionmentioning

confidence: 99%

Etranacogene dezaparvovec for hemophilia B gene therapy

Thornburg

2021

Therapeutic Advances in Rare Disease

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The treatment landscape for hemophilia has been rapidly changing with introduction of novel therapies. Gene therapy for hemophilia is a promising therapeutic option for sustained endogenous factor production to mitigate the need for prophylactic treatment to prevent spontaneous and traumatic bleeding. Etranacogene dezaparvovec is an investigational factor IX (FIX) gene transfer product that utilizes the adeno-associated virus (AAV) 5 vector with a liver-specific promoter and a hyperactive FIX transgene. Here, the development of etranacogene dezaparvovec and available efficacy and safety data from clinical trials are reviewed. Overall, etranacogene dezaparvovec provides sustained FIX expression for more than 2 years and allows for a bleed and infusion-free life in the majority of patients. Safety, efficacy, and quality-of-life data will inform shared decision-making for patients who are considering gene therapy. Long-term follow-up regarding duration of expression and safety are crucial. Plain Language Summary Factor IX Padua gene therapy to boost clotting factor and prevent bleeding for people living with hemophilia B People living with hemophilia have low or missing clotting factor, which can lead to bleeding that is unexpected or caused by a traumatic event (such as a sports injury or surgery). There are two main types of hemophilia: clotting factor (F)VIII deficiency (known as hemophilia A) and FIX deficiency (known as hemophilia B). People living with the severe or moderately severe forms of hemophilia (clotting factor levels below 3% of normal) need regular treatment, typically by infusions into the vein, to stop or prevent bleeding and damage to their joints. Gene therapy is currently being investigated as a new treatment option that introduces a working copy of the clotting factor gene to the liver. Following treatment, clotting factor is produced by the liver. Etranacogene dezaparvovec [Et-ra-na-co-gene dez-a-par-vo-vec] is a form of gene therapy for people living with hemophilia B. This form of gene therapy includes a modified form of FIX (FIX Padua) which produces high levels of FIX activity compared with normal FIX. It is being tested to see whether individuals will have low rates of bleeding and not need to treat themselves with clotting factor. In the clinical trials, participants with FIX levels below 2% (of normal) receive a single gene therapy infusion. The results of the trials have so far shown that patients given etranacogene dezaparvovec have continuous production of FIX, whereby they have reported much less bleeding and factor treatment. Questions relating to the safety of the gene therapy and how long it works will hopefully be answered through long-term follow-up of the patients once the trials are completed.

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Adult lifetime cost of hemophilia B management in the US: payer and societal perspectives from a decision analytic model

Cited by 10 publications

References 41 publications

The experiences of people with haemophilia and their families of gene therapy in a clinical trial setting: regaining control, the Exigency study

The experiences of people with haemophilia and their families of gene therapy in a clinical trial setting: regaining control, the Exigency study

Efficacy of rFIXFc versus N9-GP Prophylaxis in Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PARADIGM 2 Trials

Etranacogene dezaparvovec for hemophilia B gene therapy

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