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- Kenet, Gili, et al.
(författare)
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Continued benefit demonstrated with BAY 81-8973 prophylaxis in previously treated children with severe haemophilia A : Interim analysis from the LEOPOLD Kids extension study
- 2020
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 189, s. 96-101
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: BAY 81-8973 (Kovaltry®), a recombinant factor VIII (rFVIII) product, was efficacious and well tolerated in paediatric previously treated patients (PTPs) with severe haemophilia A for ≥50 exposure days (EDs) in the LEOPOLD Kids study. Because long-term prophylaxis (≥100 EDs) can provide substantial patient benefits, FVIII products should demonstrate long-term safety and efficacy.AIM: To demonstrate long-term (≥100 EDs) efficacy and safety of BAY 81-8973 in paediatric PTPs.METHODS: PTPs aged ≤12 years with severe haemophilia A without inhibitors could continue in the ongoing open-label extension study after completing ≥50 EDs in the LEOPOLD Kids main study. Patients received BAY 81-8973 for prophylaxis (25-50 IU/kg ≥2×/week), bleed treatment, and surgery. Bleeds were documented in electronic patient diaries. Inhibitor development was monitored every 6 months.RESULTS: At the August 2017 interim data cutoff, 46 patients (median [range] age at enrolment, 6.0 [1.0-11.0] years) had spent a median (range) of 602.5 (148-1069) EDs and 4.6 (1.0-5.9) years in the main plus extension studies. Median (quartile [Q]1; Q3) annualised bleeding rate for bleeds within 48 h after a prophylaxis infusion and total bleeds was 1.0 (0.2; 1.9) and 2.0 (0.4; 3.6), respectively. Most (>94%) bleeds were mild or moderate; 71.8% were treated with ≤1 infusion. BAY 81-8973 was also well tolerated with only one treatment-related adverse event (transient, low-titre inhibitor which did not require treatment adjustment).CONCLUSION: BAY 81-8973 was efficacious for prophylaxis and treatment of bleeds during >4.5 years in paediatric PTPs with severe haemophilia A.
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| 2. |
- Ljung, Rolf, et al.
(författare)
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BAY 81-8973 Efficacy and Safety in Previously Untreated and Minimally Treated Children with Severe Hemophilia A : The LEOPOLD Kids Trial
- 2023
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 123:1, s. 27-39
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: BAY 81-8973, a full-length recombinant factor VIII for hemophilia A treatment, has been extensively evaluated in previously treated patients in the LEOPOLD (Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease) clinical trials.AIM: To assess BAY 81-8973 efficacy and safety when used for bleed prophylaxis and treatment in previously untreated/minimally treated patients (PUPs/MTPs).METHODS: In this phase III, multicenter, open-label, uncontrolled study, PUPs/MTPs (<6 years old) with severe hemophilia A received BAY 81-8973 (15-50 IU/kg) at least once weekly as prophylaxis. Primary efficacy endpoint was the annualized bleeding rate (ABR) within 48 hours after prophylaxis infusion. Adverse events and immunogenicity were assessed. Patients who developed inhibitors were offered immune tolerance induction (ITI) treatment in an optional extension phase.RESULTS: Fifty-two patients were enrolled, with 43 patients (mean age: 13.6 months) treated. Median (interquartile range) ABR for all bleeds within 48 hours of prophylaxis infusion was 0.0 (0.0-1.8) among patients without inhibitors ( n = 20) and 0.0 (0.0-2.2) among all patients. As expected, inhibitors were the most frequent treatment-related adverse event (high titer: 17 [39.5%] patients; low titer: 6 [13.9%] patients). Six of 12 patients who underwent ITI treatment in the extension phase (high titer [ n = 5], low titer [ n = 1]) achieved a negative inhibitor titer. CONCLUSION: BAY 81-8973 was effective for bleed prevention and treatment in PUPs/MTPs. The observed inhibitor rate was strongly influenced by a cluster of inhibitor cases, and consequently, slightly higher than in other PUP/MTP studies. Overall, the BAY 81-8973 benefit-risk profile remains unchanged and supported by ongoing safety surveillance. Immune tolerance can be achieved with BAY 81-8973.
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