Optimal trough levels in haemophilia B: Raising expectations

Walsh, Christopher E.; Coppens, Michiel; Escobar, Miguel A.; Wang, Michael

doi:10.1111/hae.14098

Cited by 6 publications

(5 citation statements)

References 10 publications

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“… 4 In hemophilia B, a trough level that prevents all bleeding has not been established and is likely to vary from patient to patient based on a number of factors, including joint status and age. 5 Correlation between time spent under target trough levels and bleed rates, including spontaneous, traumatic and joint bleeds, has been demonstrated in patients with severe hemophilia B treated with recombinant FIXFc fusion protein (rFIXFc); as trough level increased, the predicted bleed rate reduced and the predicted probability of being bleed-free improved. 6 However, other contributors to the variation in hemostatic and clinical outcomes and response to treatment should be considered when determining the most appropriate prophylaxis regimen, 7 including the pharmacokinetic (PK) characteristics of the replacement factor and the patient’s individual PK profile.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of rFIXFc versus rIX-FP for the Treatment of Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PROLONG-9FP Trials

Astermark¹,

Wojciechowski²,

Aballéa³

et al. 2021

JBM

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In patients with hemophilia B, treatment with extended half-life (EHL) recombinant factor IX allows for longer dosing intervals while providing equal or superior bleeding protection compared with standard half-life products. This enables flexible, individualized treatment schedules, which reduce the burden of prophylaxis and improve patient outcomes. This analysis compared the efficacy of recombinant factor IX Fc fusion protein (rFIXFc) and recombinant factor IX albumin fusion protein (rIX-FP), two EHL therapies approved for prophylaxis and treatment of bleeding in hemophilia B. Patients and Methods: Matching-adjusted indirect treatment comparison (MAIC) was used to adjust the between-treatment differences in baseline characteristics. Individual patient data for rFIXFc (B-LONG) were matched to aggregated data for rIX-FP (PROLONG-9FP) followed by statistical comparison for estimated annualized bleeding rate (ABR) using a Poisson regression model with adjustment for over dispersion. Data were analyzed according to treatment regimen prior to study entry: prior prophylaxis (rFIXFc, n=48; rIX-FP, n=40) or prior episodic treatment (n=43 and n=19, respectively). Relative treatment effects are presented as incidence rate ratios (IRR) with 95% confidence intervals (CI). Results: After adjustment for baseline characteristics, estimated ABR observed for rFIXFc and rIX-FP was not significantly different in patients on prior prophylaxis (1.87 versus 1.58; IRR 1.18, 95% CI 0.67-2.10) or prior episodic (2.25 versus 2.22; IRR 1.01 95% CI 0.40-2.57) regimens. Conclusion:This MAIC analysis shows that the estimated ABR for rFIXFc-treated patients from B-LONG was similar to that of rIX-FP-treated patients from PROLONG-9FP and, therefore, indicates that the two EHL therapies provide similar efficacy when used as prophylaxis for patients with hemophilia B. Trough levels differ between the two products (1-3% [targeted] versus 20% [observed], respectively), suggesting that trough level is not a surrogate indicator when ABR is used as a criterion for clinical efficacy when comparing these FIX products in hemophilia B.

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Section: Introductionmentioning

confidence: 99%

Efficacy of rFIXFc versus rIX-FP for the Treatment of Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PROLONG-9FP Trials

Astermark¹,

Wojciechowski²,

Aballéa³

et al. 2021

JBM

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“…The authors thereof speculated that a poor distribution of rIX-FP to the extravascular space could be the key contributor for these results, although it has been published that extravascular distribution of rIX-FP is comparable to that of natural FIX [42,43]. Moreover, evidence to ensure that biodistribution of FIX is related to bleeding rates is still lacking, and clinical efficacy is still the most relevant outcome to assess treatment success [44,45]. In a third report, 3 out of the 7 patients treated with rIX-FP reported unexpected bleeding episodes.…”

Section: Real-world Evidence Using Rix-fpmentioning

confidence: 99%

Expert opinion paper on the treatment of hemophilia B with albutrepenonacog alfa

Roman

Benítez

Canaro

et al. 2021

Expert Opinion on Biological Therapy

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Introduction: Current guidelines recommend prophylactic treatment of hemophilia B with the missing coagulation factor IX, either with standard half-life or extended half-life products. Extended half-life products have half-lives three to six times longer than the former, allowing a reduction in the number of weekly injections and therefore, potentially impacting on treatment adherence and quality of life. Albutrepenonacog alfa is an extended half-life fusion protein of coagulation factor IX with recombinant human albumin, indicated for both on-demand and prophylactic treatment for bleeding in patients with hemophilia B of all ages. Areas covered: The authors review the clinical and pharmacokinetic characteristics of albutrepenonacog alfa, as well as the available information regarding trough levels and real-world evidence. Given the availability of other factor IX products in the market, indirect comparisons of clinical and pharmacokinetic characteristics are presented. Expert opinion: The authors exhibit their expert opinion on which patient profiles are candidates for prophylactic treatment with albutrepenonacog alfa, and on the management of patients in terms of dosing, regimens of administration and protocols for switching the treatment.

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“…6,7 FIX activity levels fluctuate and people with haemophilia B (PwHB) may experience bleeds. 8 Joint damage can occur despite prophylaxis, resulting from inadequate control of clinical and subclinical bleeding. 3,9,10 The time required for administration of prophylaxis negatively affects HRQoL by interfering with daily activities, relationships, and decisions regarding careers or education.…”

Section: Introductionmentioning

confidence: 99%

“…FIX replacement adherence can be difficult, with 25% of people with haemophilia aged 18−30 years being non‐adherent, and some choosing to decrease their dosing frequency to mitigate this burden 6,7 . FIX activity levels fluctuate and people with haemophilia B (PwHB) may experience bleeds 8 . Joint damage can occur despite prophylaxis, resulting from inadequate control of clinical and subclinical bleeding 3,9,10 .…”

Section: Introductionmentioning

confidence: 99%

Effect of etranacogene dezaparvovec on quality of life for severe and moderately severe haemophilia B participants: Results from the phase III HOPE‐B trial 2 years after gene therapy

Itzler,

Buckner,

Leebeek

et al. 2024

Haemophilia

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IntroductionFor people with haemophilia B (PwHB), bleeding may occur despite prophylaxis, negatively affecting health‐related quality of life (HRQoL). The pivotal phase 3 HOPE‐B trial investigating the adeno‐associated virus gene transfer product, etranacogene dezaparvovec (EDZ), demonstrated sustained factor IX (FIX) activity and bleed protection in PwHB with baseline FIX levels ≤2%.AimAssess how EDZ affects HRQoL in HOPE‐B trial participants.MethodsHRQoL was evaluated using generic and disease‐specific patient reported outcomes (PROs) including the EQ‐5D‐5L and the Hem‐A‐QoL questionnaires. Mean domain and total scores were compared 6 months pre‐ and the first 2 years post‐EDZ administration using repeated measures linear mixed models. The percentage of participants with minimal clinically important improvements in HRQoL was also evaluated.ResultsTwo years post‐EDZ, there were nominally significant increases in the least squares (LS) mean score for the EQ‐5D‐5L Index Value (.04; p = .0129), reflecting better HRQoL. Nominally significant decreases in the LS mean scores, reflecting better HRQoL, were also found for the Hem‐A‐QoL total score (−6.0; p < .0001) and the Treatment (−13.94; p < .0001), Feelings (−9.01; p < .0001), Future (−6.45; p = .0004) and Work/School (−5.21; p = .0098) domains. The percentage of participants with ≥15‐point improvement ranged from 45.83% (95% CI: 31.37%, 60.83%) for Treatment to 13.89% (95% CI: 4.67%, 29.50%) for Family Planning. Results were similar for Year 1.ConclusionIn conclusion, gene therapy with EDZ improved HRQoL in the first and second years in several Hem‐A‐QoL domains, including Treatment, Feelings, Work/School and Future domains, whereas improvement in other aspects of HRQoL were not demonstrated.

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Optimal trough levels in haemophilia B: Raising expectations

Cited by 6 publications

References 10 publications

Efficacy of rFIXFc versus rIX-FP for the Treatment of Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PROLONG-9FP Trials

Efficacy of rFIXFc versus rIX-FP for the Treatment of Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PROLONG-9FP Trials

Expert opinion paper on the treatment of hemophilia B with albutrepenonacog alfa

Effect of etranacogene dezaparvovec on quality of life for severe and moderately severe haemophilia B participants: Results from the phase III HOPE‐B trial 2 years after gene therapy

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