rVIII-SingleChain: results of a phase III PK, efficacy and safety study in children less than 12 years of age with severe hemophilia A

I. Pabinger1, O. Stasyshyn2, G. Iosava3, C. Djambas Khayat4, J. Ong5, K. Fischer6, F. Abdul Karim7, A. Veldman8, K. St. Ledger9 (1Vienna, Austria, 2Lviv, Ukraine, 3Tbilisi, Georgia, 4Beirut, Lebanon, 5Davao, Philippines, 6Ultrecht, Netherlands, 7Kuala Lumpur, Malaysia, 8Marburg, Germany, 9King of Prussia, PA, United States)

Bleeding disorders, coagulation and fibrinolytic factors
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: rVIII-SingleChain, a novel B-domain truncated recombinant Factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, was shown to have a higher binding affinity to von Willebrand Factor (VWF) leading to an improved pharmacokinetic (PK) profile. Safety, efficacy and PK of rVIII-SingleChain were investigated in previously treated pediatric patients <12 years of age with severe hemophilia A in a phase III study.

Methods: Patients with severe hemophilia A (endogenous FVIII <1%), <12 years of age, and with more than 50 previous exposure days (EDs) to FVIII products received either on-demand or prophylactic infusions of rVIII-SingleChain.

Results: A total of 84 patients were included in the study (0 to <6 years, n=35; ≥6 to <12 years, n=49). Thirty-nine patients underwent a PK evaluation (0 to <6 years, n=20; ≥6 to <12 years, n=19); younger and older pediatric patients had similar PK and FVIII activity profiles. Mean PK parameters for patients 0 to <6 years and patients ≥6 to <12 years, were; AUCinf: 1080 and 1170 IU*h/dL, clearance: 5.07 and 4.63 mL/h/kg, and half-life: 10.4 and 10.2 h, respectively. Of the 81 patients on prophylaxis, 83% were on twice weekly (n=43, 53%) or three-times weekly (n=25, 31%) regimens. The median starting doses were 35 and 32 IU/mL, respectively. Three patients were assigned to an on-demand regimen. Hemostatic efficacy was rated as excellent or good in 96.3% of the 347 treated bleeds evaluated by the investigator. The median annualized spontaneous bleeding rate (AsBR) was 0.00 (Q1, Q3: 0.00, 2.20), the median annualized bleeding rate (ABR) was 3.69 (Q1, Q3: 0.00, 7.20), and the median joint ABR was 1.62 (Q1, Q3: 0.0, 4.87) across all prophylaxis regimens. The total cumulative exposure during the study was 5239 EDs, with 65 participants reaching >50 ED (0 to <6 years, n=27; ≥6 to <12 years, n=38). Tolerability was excellent, 99.4% of 4774 injections were assessed as producing no reaction. The adverse event profile was in line with the expected background pathology for pediatric patients with severe hemophilia A. No patient had a serious AE related to rVIII-SingleChain, and no patient developed an inhibitor during this study.

Conclusion: The novel rFVIII molecule, rVIII-SingleChain, has demonstrated excellent hemostatic efficacy with a positive safety profile in a clinical study in children <12 years of age with severe hemophilia A.