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Extension Study With rVIII-SingleChain in Previously Untreated Patients (PUPs) With Severe Haemophilia A
Johnny Mahlangu1, Maria Elisa Mancuso2,3, Kathelijn Fischer4
1Department of Molecular Medicine and Haematology, University of the Witwatersrand and NHLS, Johannesburg, Gauteng, South Africa.
Insights
RVIII-SingleChain is safe and effective for previously untreated patients with haemophilia A, showing high treatment success and low bleeding rates. It also effectively eradicates inhibitors, demonstrating a favorable benefit-risk profile.
Area of Science:
- Haematology
- Pharmacology
- Clinical Research
Background:
- Previous studies confirmed rVIII-SingleChain's efficacy and safety in previously treated haemophilia A patients.
- Haemophilia A is a genetic bleeding disorder requiring effective treatment to prevent bleeding and long-term complications.
Purpose of the Study:
- To evaluate the safety and efficacy of rVIII-SingleChain in previously untreated patients (PUPs) with severe haemophilia A.
- To assess inhibitor development, treatment success for bleeding events, and bleeding rates in PUPs.
Main Methods:
- An open-label, Phase 3 extension study enrolled 24 PUPs with severe haemophilia A.
- Patients received rVIII-SingleChain prophylactically or on-demand.
- Primary endpoints included high-titre inhibitor formation, treatment success for major bleeds, and annualised spontaneous bleeding rate (AsBR).
Main Results:
- Six PUPs developed high-titre inhibitors and six developed low-titre inhibitors.
- Treatment success for bleeding events was 92.1%.
- Prophylactic therapy in inhibitor-negative PUPs resulted in a median AsBR of 0.52.
Conclusions:
- RVIII-SingleChain demonstrated a satisfactory benefit-risk profile in PUPs.
- The treatment showed a high success rate for bleeding events and a low AsBR during prophylaxis.
- RVIII-SingleChain was effective in eradicating inhibitors in PUPs.
Introduction:
Clinical trials and real-world evidence have demonstrated the efficacy and safety of rVIII-SingleChain in previously treated patients with haemophilia A.
Aim:
To investigate the safety and efficacy of rVIII-SingleChain in previously untreated patients (PUPs).
Methods:
In an open-label, phase 3, extension study, PUPs with severe haemophilia A (FVIII <1%) received rVIII-SingleChain prophylactically or on-demand. The primary endpoints were incidence of high-titre (HT) inhibitor formation to FVIII, treatment success for major bleeding episodes and annualised spontaneous bleeding rate (AsBR).
Results:
Twenty-four PUPs (median age 1 year [range 0-5]) were treated with rVIII-SingleChain; median time on study was 35.0 months (range 2.4-54.0). Overall, six PUPs developed a HT inhibitor (>5 BU/mL) and six developed a low-titre (LT) inhibitor (≤5 BU/mL). The median number of exposure days at inhibitor development was 10 (interquartile range [IQR] 5.0-14.0). Of 11 inhibitor-positive PUPs (five HT, six LT) who continued rVIII-SingleChain therapy, nine (81.8%; three HT, six LT) achieved inhibitor eradication (<0.6 BU/mL). Median time to eradication was 14.3 weeks (IQR 9.8-53.8). Seventeen treatment-emergent adverse events in 12 PUPs (50.0%) were related to rVIII-SingleChain, mainly inhibitor development (14/17 events). Treatment was successful (haemostatic efficacy rated excellent or good) for 290/315 bleeding events (92.1%). During prophylactic therapy, inhibitor-negative PUPs had a median (IQR) AsBR of 0.52 (0.00-4.99) and annualised bleeding rate of 1.98 (0.77-11.23).
Conclusion:
RVIII-SingleChain demonstrated a satisfactory benefit:risk profile in PUPs, with a high treatment success rate and a low AsBR during prophylaxis, and was effective at eradicating inhibitors.
