Eptacog beta efficacy and safety in the treatment and control of bleeding in paediatric subjects (&lt;12 years) with haemophilia A or B with inhibitors

Pipe, Steven W.; Hermans, Cédric; Chitlur, Meera; Carção, Manuel; Castaman, Giancarlo; Davis, Joanna; Ducore, Jonathan M.; Dunn, Amy L.; Escobar, Miguel A.; Journeycake, Janna M.; Khan, Osman; Mahlangu, Johnny; Meeks, Shannon L.; Mitha, Ismail; Négrier, Claude; Nowak‐Göttl, Ulrike; Recht, Michael; Chrisentery‐Singleton, Tammuella; Stasyshyn, Oleksandra; Vilchevska, Kateryna; Villarreal‐Martínez, Laura; Wang, Michael; Windyga, Jerzy; Young, Guy; Alexander, W. Allan; Bonzo, Daniel; Macie, Christopher; Mitchell, Ian S.; Sauty, Evelyne; Wilkinson, Thomas A.; Shapiro, Amy D.

doi:10.1111/hae.14563

Cited by 10 publications

(7 citation statements)

References 29 publications

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“…42 The median time to response was 5.98 h in the eptacog beta 75 µg/kg months of age were randomised to receive the eptacog beta 75 µg/kg (n = 12) or 225 µg/kg (n = 13) IDR using the same infusion frequency schedule and cross-over design as in PERSEPT 1. 45 In total, the participants had 546 mild or moderate bleeds and 3 severe bleeds (spontaneous renal haemorrhage, traumatic intracranial bleed and traumatic left elbow bleed). 45 The median number of events per participant was 17.…”

Section: Key Resultsmentioning

confidence: 99%

“…45 In total, the participants had 546 mild or moderate bleeds and 3 severe bleeds (spontaneous renal haemorrhage, traumatic intracranial bleed and traumatic left elbow bleed). 45 The median number of events per participant was 17. 42 As for the PERSEPT 1 study, the focus of the EMA analysis of data from PERSEPT 2 was the successful treatment of bleeds of any severity at 12 h (primary endpoint), defined as a 'good' or 'excellent' response on the 4-point haemostasis evaluation scale (Table S2), assessed by the parent/caregiver of the participant or the physician for severe bleeds.…”

Section: Key Resultsmentioning

confidence: 99%

“…PERSEPT 2, a prospective, multicentre, randomised, open‐label, cross‐over Phase III study, was undertaken to evaluate the efficacy, safety and immunogenicity of eptacog beta for the treatment of bleeds in a paediatric population (<12 years of age)—the first prospective study of a rFVIIa to enrol an exclusively paediatric population 45 . In this global study, 25 children (<6 years of age: n = 13; ≥6 to <12 years of age: n = 12) with congenital haemophilia A or B and inhibitors (≥5 BU or those with <5 BU who were expected to have a high anamnestic response to FVIII or FIX, or be refractory to increased dosing of FVIII or FIX) who had ≥3 bleeds in the previous 6 months or since birth if <6 months of age were randomised to receive the eptacog beta 75 µg/kg ( n = 12) or 225 µg/kg ( n = 13) IDR using the same infusion frequency schedule and cross‐over design as in PERSEPT 1 45 …”

Section: Clinical Efficacy In Phase III Studies: Persept 1 2 Andmentioning

confidence: 99%

“…44 Pain was successfully relieved 12 h after dosing in 91.6% (95% CI 84.8−98.4) and 89.9% (95% CI 82.2−97.6) of bleeds treated with the eptacog beta 75 µg/kg and 225 µg/kg IDRs, respectively (data on file) 44. In summary, in PERSEPT 1, eptacog beta rapidly controlled bleeds in adults and adolescents with haemophilia A or B and inhibitors, with a TA B L E 2 PERSEPT 2, a prospective, multicentre, randomised, open-label, crossover Phase III study, was undertaken to evaluate the efficacy, safety and immunogenicity of eptacog beta for the treatment of bleeds in a paediatric population (<12 years of age)-the first prospective study of a rFVIIa to enrol an exclusively paediatric population 45. In this global study, 25 children (<6 years of age: n = 13; ≥6 to <12 years of age: n = 12) with congenital haemophilia A or B and inhibitors (≥5 BU or those with <5 BU who were expected to have a high anamnestic response to FVIII or FIX, or be refractory to increased dosing of FVIII or FIX) who had ≥3 bleeds in the previous 6 months or since birth if <6…”

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confidence: 99%

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Eptacog beta for the management of patients with haemophilia A and B with inhibitors: A European perspective

Miesbach,

Carcao,

Mahlangu

et al. 2024

Haemophilia

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Eptacog beta (activated), a recombinant human factor VIIa (rFVIIa), was approved by the US Food and Drug Administration (FDA) in 2020 (SEVENFACT®, LFB & HEMA Biologics) and the European Medicines Agency (EMA) in 2022 (CEVENFACTA®, LFB). In Europe, eptacog beta is indicated for the treatment of bleeds and the prevention of bleeds during surgery or invasive procedures in adults and adolescents (≥12 years old) with congenital haemophilia A or B with high‐titre inhibitors (≥5 BU) or with low‐titre inhibitors who are expected to have a high anamnestic response to factor VIII or factor IX, or to be refractory to increased dosing of these factors. The efficacy and safety of eptacog beta were evaluated in three Phase III clinical studies, PERSEPT 1, 2 and 3. For the EMA filing dossier, the analysis of data from PERSEPT 1 and 2 differed from the analysis used to support the filing in the US. In this review, we summarise current data regarding the mode of action, clinical efficacy and safety of eptacog beta for the management of haemophilia A and B in patients with inhibitors from a European perspective. In addition to providing a valuable summary of the analyses of the clinical data for eptacog beta conducted for the EMA, our review summarises the potential differentiators for eptacog beta compared with other current bypassing agents.

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Section: Key Resultsmentioning

confidence: 99%

Section: Key Resultsmentioning

confidence: 99%

Section: Clinical Efficacy In Phase III Studies: Persept 1 2 Andmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Eptacog beta for the management of patients with haemophilia A and B with inhibitors: A European perspective

Miesbach,

Carcao,

Mahlangu

et al. 2024

Haemophilia

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“…To verify the exposure matching strategy in a plausible trial design of 24 pediatric subjects, 1000 clinical trials were simulated. The total number of 24 pediatric subjects was considered reasonable due to difficulties in recruiting subjects with HA/HB with inhibitors, and have recently been justified with respect to efficacy in another pediatric program for an rFVIIa compound that was evaluated in a similar setup as planned for MarzAA 42,43 . For each trial, each pediatric patient AUC 0‐24h and C max(0‐24h) was compared to the adult matching range.…”

Section: Discussionmentioning

confidence: 99%

Model‐informed pediatric dose selection of marzeptacog alfa (activated): An exposure matching strategy

Faraj

Wijk

Neuman

et al. 2023

CPT Pharmacom & Syst Pharma

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Marzeptacog alfa (activated) (MarzAA) is an activated recombinant human rFVII variant intended for subcutaneous (s.c.) administration to treat or prevent bleeding in individuals with hemophilia A (HA) or B (HB) with inhibitors, and other rare bleeding disorders. The s.c. administration provides benefits over i.v. injections. The objective of the study was to support the first-in-pediatric dose selection for s.c. MarzAA to treat episodic bleeding episodes in children up through 11 years in a registrational phase III trial. Assuming the same exposure-response

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Current status and future prospects of activated recombinant coagulation factor VIIa, NovoSeven®, in the treatment of haemophilia and rare bleeding disorders

Shima

2023

Ann Hematol

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rFVIIa, a human recombinant activated coagulation factor VII, has been used worldwide for more than two decades for the treatment of bleeding episodes and prevention of bleeding in patients undergoing surgery/invasive procedures with congenital haemophilia A or B with inhibitors (CHwI A or B), acquired haemophilia (AH), congenital factor VII deficiency and Glanzmann thrombasthenia (GT), refractory to platelet transfusion. The approved dosage, administration and indication of rFVIIa in the US, Europe and Japan differ, depending on the needs of the patient population and regulatory practices. This review presents an overview of the current status and future prospects, including that from a Japanese perspective, of using rFVIIa in the treatment of approved indications. The efficacy and safety of rFVIIa in the approved indications has been demonstrated in several randomised and observational studies and data from registries. The overall incidence of thrombosis across all approved indications in a retrospective safety assessment of clinical trials and registries, prelicensure studies and postmarketing surveillance studies of rFVIIa use was 0.17%. Specifically, the risk of thrombotic events was 0.11% for CHwI, 1.77% for AH, 0.82% for congenital factor VII deficiency and 0.19% for GT. Emerging non-factor therapies such as emicizumab have changed the treatment landscape of haemophilia A, including preventing bleeding in patients with CHwI. However, rFVIIa will continue to play a significant role in the treatment of such patients, particularly during breakthrough bleeding or surgical procedures.

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Eptacog beta efficacy and safety in the treatment and control of bleeding in paediatric subjects (<12 years) with haemophilia A or B with inhibitors

Cited by 10 publications

References 29 publications

Eptacog beta for the management of patients with haemophilia A and B with inhibitors: A European perspective

Eptacog beta for the management of patients with haemophilia A and B with inhibitors: A European perspective

Model‐informed pediatric dose selection of marzeptacog alfa (activated): An exposure matching strategy

Current status and future prospects of activated recombinant coagulation factor VIIa, NovoSeven®, in the treatment of haemophilia and rare bleeding disorders

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