Abstract Number: PB0918
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: BAY 94‑9027 (Jivi®) is a B-domain-deleted recombinant factor VIII product, site‑specifically PEGylated to extend half-life, approved in the US, EU, Japan and Canada for previously treated patients with severe hemophilia A, aged ≥12 years. The phase 2/3 PROTECT VIII main study and its extension demonstrated safety and efficacy of BAY 94‑9027.
Aims: To report final safety data, including treatment-emergent adverse events (TEAEs) and markers of renal and hepatic function, in patients who participated in the PROTECT VIII extension.
Methods: In the PROTECT VIII extension, 121 patients received BAY 94-9027 on demand (n=14) or prophylaxis (n=107; 30-40 IU/kg twice-weekly, 45-60 IU/kg every 5 days or 60 IU/kg every 7 days). Safety endpoints included TEAEs, laboratory markers, and FVIII inhibitor development.
Results: At extension completion, median (range) time in study was 3.9 (0.8-7.0) years, of which time in extension was 3.2 (0.1; 6.3) years with a median (range) of 175 (9-621) exposure days; 36 patients had >5 years of BAY 94-9027 treatment in total. During extension, 10 (71.4%) on-demand and 86 (80.4%) prophylaxis patients reported TEAEs (Table 1). Ten (8.3%) patients experienced study drug-related TEAEs (most common types were musculoskeletal disorders [n=4] and laboratory abnormal results [n=3]). Study drug-related serious adverse events occurred in two (1.7%) patients (elevated liver function tests and migratory back pain, respectively), both leading to study drug discontinuation. At the final study visit, patients had similar levels of markers of renal and hepatic function to baseline (Table 2). No patients developed FVIII inhibitors. No deaths or thrombotic events, including thrombotic microangiopathy, were reported.
Conclusions: BAY 94-9027 was well-tolerated during the PROTECT VIII extension and no patients developed FVIII inhibitors. Low levels of study drug-related TEAEs, and no specific changes in markers of renal and liver hepatic function were detected over ≥5 years of observation of BAY 94-9027 treatment.
| On demand (n = 14) |
Total prophylaxis (n = 107) |
Total (N = 121) |
|
| Time in extension, years, median (range) | 3.2 (0.6-4.1) | 3.2 (0.1-6.3) | 3.2 (0.1-6.3) |
| Exposure days in extension, median (range) | 101.5 (13-176) | 211.0 (9-621) | 175.0 (9-621) |
Number of patients (%) |
|||
| Any TEAE | 10 (71.4) | 86 (80.4) | 96 (79.3) |
| Any study drug-related TEAE | 0 | 10 (9.3) | 10 (8.3) |
| Any SAE | 2 (14.3) | 34 (31.8) | 36 (29.8) |
| Any study drug-related SAE | 0 | 2 (1.9) | 2 (1.7) |
| Discontinuation of study drug due to AE | 0 | 2 (1.9) | 2 (1.7) |
| Deaths | 0 | 0 | 0 |
[Table 1: Summary of TEAEs at the end of PROTECT VIII extension]
| On demand | Total prophylaxis | Total | ||||
| Serum creatinine level at final study visit, median (Q1; Q3), mg/dL | n = 14 | 0.718 (0.679; 0.973) |
n = 98 | 0.837 (0.746; 0.961) |
n = 112 | 0.820 (0.724; 0.961) |
| Serum creatinine, median (Q1; Q3) change from baseline, mg/dL | n = 14 | −0.051 (−0.079; 0.045) |
n = 98 | −0.040 (−0.102; 0.034) |
n = 112 | 0.040 (−0.102; 0.034) |
| Serum creatinine clearance at final study visit, median (Q1; Q3), mL/min (calculated) | n = 14 | 134.4 (98.3; 174.7) |
n = 98 | 128.1 (104.6; 149.1) |
n = 112 | 128.1 (104.1; 151.0) |
| Serum creatinine clearance, median (Q1; Q3) change from baseline, mL/min (calculated) | n = 14 | 8.92 (−4.80; 16.31) |
n = 98 | 5.15 (−4.44; 17.92) |
n = 112 | 5.25 (−4.55; 16.77) |
| Serum ALT level at final study visit, median (Q1: Q3), U/L | n = 14 | 26.5 (18.0; 37.0) |
n = 98 | 23.0 (17.0; 40.0) |
n = 112 | 24.0 (17.0; 40.0) |
| Serum ALT, median (Q1; Q3) change from baseline, U/L | n = 13 | −4.00 (−24.00; 6.00) |
n = 96 | −1.00 (−9.00; 4.50) |
n = 109 | −1.00 (−9.00; 5.00) |
| Serum AST level at final study visit, median (Q1: Q3), U/L | n = 14 | 23.5 (18.0; 30.0) |
n = 98 | 22.0 (18.0; 28.0) |
n = 112 | 22.0 (18.0; 28.5) |
| Serum AST, median (Q1; Q3) change from baseline, U/L | n = 13 | −3.00 (−15.00; 0.00) |
n = 95 | −1.00 (−7.00; 1.00) |
n = 108 | −1.50 (−7.00; 1.00) |
[Table 2: Markers of renal or hepatic function at the end of PROTECT VIII extension. Not all patients had biomarker data available.]
To cite this abstract in AMA style:
Oldenburg J, Ducore JM, Tarango C, Simpson ML, Wang M, Maas Enriquez M, Lalezari S. Final Safety Outcomes Following ≥5 Years’ Observation of BAY 94-9027 Treatment in Patients with Hemophilia A in the PROTECT VIII Extension [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/final-safety-outcomes-following-%e2%89%a55-years-observation-of-bay-94-9027-treatment-in-patients-with-hemophilia-a-in-the-protect-viii-extension/. Accessed November 29, 2023.« Back to ISTH 2020 Congress
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