A French Real-World Evidence Study Evaluating the Efficacy, Safety, and Pharmacokinetic Parameters of rVIII-SingleChain in Patients with Hemophilia A Receiving Prophylaxis

Guillet, Benoît; Hassoun, Abel; Wibaut, B.; Harroche, Annie; Biron‐Andréani, Christine; Repesse, Yohann; d’Oiron, Roseline; Tardy, B.; Pan‐Petesch, Brigitte; Chamouni, Pierre; Gay, Valérie; Fouassier, Marc; Pouplard, Claire; Martin, C. Nuernberger; Catovic, Hasan; Delavenne, Xavier

doi:10.1055/s-0043-1761449

Cited by 3 publications

(4 citation statements)

References 45 publications

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“…For instance, a recent RWE study of patients switching from SHL products to rVIII-SingleChain in France found improved PK versus clinical trial data. 14 Real-world data are particularly relevant for rare diseases, confirming effectiveness of treatments, taking 'non-ideal' patients into consideration, and enabling assessment of subpopulations and small populations.…”

Section: Discussionmentioning

confidence: 99%

“…Also, analyses of patients switching from a rFVIII product to another, particularly in real‐world studies, may be helpful in informing treatment decisions by overcoming the limitations of comparing PK data between different studies. For instance, a recent RWE study of patients switching from SHL products to rVIII‐SingleChain in France found improved PK versus clinical trial data 14 . Real‐world data are particularly relevant for rare diseases, confirming effectiveness of treatments, taking ‘non‐ideal’ patients into consideration, and enabling assessment of subpopulations and small populations.…”

Section: Discussionmentioning

confidence: 99%

“…2 However, using this definition, only PEGylated or Fc fusion products meet EHL criteria (BAX 855, rFVIIIFc, BAY 94−9027, and N8-GP met all three criteria, while KOVALTRY (BAY 81-8973), NUWIQ (Humancl rhFVIII), and rVIII-SingleChain did not fully meet the criteria) 2 ; also, this categorisation is not consistently followed in the literature, for example, rVIII-SingleChain is considered an EHL product in published papers and described as a 'prolonged half-life' product on the Online Clotting Factor Concentrates (CFC) Registry on the WFH website. [12][13][14] The ISTH defines 'activity over time' (e.g., time to 1% [T1%] and time to 5% [T5%]) as the most intuitive information for building treatment regimens and deliver information 15 It is also possible that classifications by clinical outcomes (efficacy, safety, or quality of life) may be feasible across rFVIII products. However, currently these are not recommended for FVIII replacement product classification.…”

Section: Introductionmentioning

confidence: 99%

“…In 2018, Mahlangu et al., proposed the following definition for EHL products: (i) use of technology designed to extend rFVIII half‐life; (ii) not bioequivalent with standard rFVIII comparator (above the U.S. Food and Drug Administration [FDA]/European Medicines Agency [EMA] cut‐off of 125% for the 90% confidence intervals [CIs] for area under the curve [AUC] ratio) and (iii) EHL ratio in a pharmacokinetic (PK) comparator crossover study 2 . However, using this definition, only PEGylated or Fc fusion products meet EHL criteria (BAX 855, rFVIIIFc, BAY 94−9027, and N8‐GP met all three criteria, while KOVALTRY (BAY 81–8973), NUWIQ (Human‐cl rhFVIII), and rVIII‐SingleChain did not fully meet the criteria) 2 ; also, this categorisation is not consistently followed in the literature, for example, rVIII‐SingleChain is considered an EHL product in published papers and described as a ‘prolonged half‐life’ product on the Online Clotting Factor Concentrates (CFC) Registry on the WFH website 12–14 …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Classification of recombinant factor VIII products and implications for clinical practice: A systematic literature review

Ay,

Napolitano,

Hassoun

et al. 2024

Haemophilia

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IntroductionConsensus over the definition of recombinant factor VIII (rFVIII) product classification in haemophilia A is lacking. rFVIII products are often classified as standard half‐life (SHL) or extended half‐life (EHL); despite this, no universally accepted definition currently exists. One proposed definition includes half‐life, area under the curve, and technology designed to extend half‐life; however, the International Society on Thrombosis and Haemostasis defines activity over time as the most intuitive information for building treatment regimens and the World Federation of Hemophilia describes rFVIII product classification in terms of infusion frequency.AimTo summarise published data on the clinical and pharmacokinetic criteria used to define rFVIII product classification.MethodsPubMed and EMBASE database searches of English‐language articles (2002–2022) were conducted using search strings to identify the relevant population, intervention, and outcomes (e.g., clinical and pharmacokinetic parameters). Articles then underwent title/abstract and full‐text screens.ResultsAmong 1147 identified articles, 62 were included. Half‐life was the most widely reported outcome with no clear trends or product groupings observed. No clear groupings emerged among other outcomes, including infusion frequency, consumption, and efficacy. As activity over time was reported in few articles, further investigation of its relevance to rFVIII product classification is warranted.ConclusionThe findings of this systematic literature review suggest that parameters other than half‐life might be important for the development of a comprehensive and clinically relevant rFVIII product classification definition. There seems to be an opportunity to consider parameters that are clinically meaningful and useful for shared decision‐making in haemophilia A treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Classification of recombinant factor VIII products and implications for clinical practice: A systematic literature review

Ay,

Napolitano,

Hassoun

et al. 2024

Haemophilia

Self Cite

View full text Add to dashboard Cite

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Switching hemophilia A patients to rVIII-SingleChain: The Iberian experience

Calvo-Villas,

Núñez-Vázquez,

Benítez-Hidalgo

et al. 2024

Medicine

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The real-world outcomes of lonoctocog alfa (rVIII-SingleChain), a long-acting factor VIII (FVIII) with a favorable safety and efficacy profile in trials, were assessed in patients with hemophilia A in Iberian (Spain and Portugal). This was a retrospective study involving patients switching to rVIII-SingleChain from other FVIIIs in 7 Spanish and Portuguese hospitals. The efficacy and safety of replacement therapies were compared between 12 months before switching and the period from switching to the end of the study. Twenty-nine patients (median age 25 years; severe hemophilia A, 37.9%) were recruited. Before switching, 12 were on prophylaxis and were followed-up for a median of 12 months. After switching, 17 received prophylaxis with rVIII-SingleChain and were followed-up for a median of 41 months. Those with ≤2 weekly infusions increased from 37.5% before switching to 60.7% after switching to rVIII-SingleChain. The median monthly consumption was 312 IU/kg with prior FVIIIs and 273 IU/kg with rVII-SingleChain. Six spontaneous bleeds were reported in each period in the prophylaxis patients. In the entire cohort, 50 bleeds were reported with prior FVIIIs and 33 were reported after switching to rVIII-SingleChain. Patients requiring ≤1 dose for hemostasis increased from 44.0% with prior FVIIIs to 60.6% with rVIII-SingleChain. Responses were rated good/excellent in 95.4% of cases. No safety concerns were reported. Patients who switched to rVIII-SingleChain prophylaxis had excellent bleeding control and reduced infusion frequency in regular clinical practice, with the subsequent increase in quality-of-life.

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Comprehensive laboratory assessment of lonoctocog alfa versus octocog alfa in severe haemophilia A

Müller,

Albert,

Klein

et al. 2024

Haemophilia

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IntroductionLonoctocog alfa is a single‐chain factor VIII (FVIII) molecule with high binding affinity to von‐Willebrand‐factor. While it is well known that its plasma activity is underestimated by one‐stage clotting assays (OSCA), there is a lack of knowledge on the post‐infusion performance of lonoctocog alfa in global coagulation assays or its potential impact on the haemostatic balance in vivo.AimTo characterize lonoctocog alfa versus octocog alfa in pre‐ and post‐infusion samples obtained from patients undergoing repeated investigation of incremental recovery (IR).MethodsEighteen patients with severe haemophilia A (lonoctocog alfa: 10, octocog alfa: 8) were included. A panel of factor‐specific and global coagulation assays was applied, comprising a FVIII OSCA, two FVIII chromogenic substrate assays (CSA), rotational thrombelastography and thrombin generation (TG). Potential activation of coagulation was assessed by measuring plasma thrombin markers and levels of activated protein C.ResultsComparable IRs were found for lonoctocog alfa and octocog alfa (2.36 [IU/dL]/[IU/kg] vs. 2.55 [IU/dL]/[IU/kg], respectively). Lonoctocog alfa activities were found to be underestimated by the FVIII OSCA while also the two FVIII CSAs showed statistically significant assay discrepancies on lonoctocog alfa. Effects of both FVIII products on rotational thrombelastography were less distinct than those on TG parameters. No elevated pre‐ or significantly shifting post‐infusion plasma levels of coagulation biomarkers were detected.ConclusionLonoctocog alfa and octocog alfa showed comparable recovery and safety in vivo as well as similar impacts on TG in vitro. Observed assay discrepancies on lonoctocog alfa demonstrated variability of results also between different FVIII CSAs.

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A French Real-World Evidence Study Evaluating the Efficacy, Safety, and Pharmacokinetic Parameters of rVIII-SingleChain in Patients with Hemophilia A Receiving Prophylaxis

Cited by 3 publications

References 45 publications

Classification of recombinant factor VIII products and implications for clinical practice: A systematic literature review

Classification of recombinant factor VIII products and implications for clinical practice: A systematic literature review

Switching hemophilia A patients to rVIII-SingleChain: The Iberian experience

Comprehensive laboratory assessment of lonoctocog alfa versus octocog alfa in severe haemophilia A

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