Consumption Of FVIII Concentrate During On-Demand and Prophylactic Treatment With Human-cl rhFVIII In Prospective Clinical Studies In Adult Patients With Severe Hemophilia A

There is ample evidence to support prophylactic treatment with factor VIII (FVIII) in children with severe hemophilia A (HA). Adults with severe HA are often treated on-demand and the potential benefit of regular prophylaxis is linked to a higher consumption of FVIII concentrates. During the clinical development of Human-cl rhFVIII, the first recombinant FVIII concentrate from a human cell line, its efficacy and safety was evaluated in previously treated adult patients (PTPs) during on-demand treatment only (GENA-01) and prophylaxis (GENA-08).

To compare post-hoc the annualized bleeding rate (ABR) and the consumption of FVIII concentrate in patients treated exclusively on-demand with those treated prophylactically.

Both prospective multi-centre studies were approved by the Ethics Committees of each participating institution and informed consent was obtained from the patient prior to any trial activity. In GENA-01, patients were to be treated on-demand for ≥6 months and ≥50 exposure days with protocol recommended doses ranging from 20 to 60 IU/kg, depending on the severity of the bleed. In GENA-08, patients were to be treated prophylactically with Human-cl rhFVIII every other day with 30-40 IU/kg for ≥6 months. Human-cl rhFVIII was also to be used in case of breakthrough bleeds.

22 PTPs with severe HA were enrolled in GENA-01, and 32 in GENA-08. The study populations were reasonably well comparable to each other (GENA-01 vs. GENA-08, mean±SD), regarding age (39.6±14.1 vs. 37.3±13.6 years), body mass index (23.9±4.8 vs. 25.8±4.9 kg/m²), hemophilia joint health score (38.4±30.3 vs. 34.6±32.2), race (>80% White in both studies) and historical bleeding sites. In GENA-08, the majority of patients (65.6%) had been treated prophylactically prior to study entry. Their historical mean±SD ABR was 6.6 ±11.3 (median: 2.0, range: 0-48.7) and their mean prophylactic dose/month was 293 IU/kg. The other 11 patients who had been treated on-demand had a mean±SD ABR of 47.4±34.6 (median: 36.5, range: 12.2-121.7). In GENA-01, all but 2 patients were treated on-demand prior to study entry. The historical mean±SD ABR of all GENA-01 patients was 49.5±35.9 (median: 44.6, range: 2.0-158.7). The ABR and FVIII consumption during the studies are shown in Table 1.

The data suggest that regular prophylactic treatment with Human-cl rhFVIII in adult PTPs with severe HA resulted in an approximately 25-fold reduction of bleeding rate, and a 3-fold increase of FVIII concentrate consumption.

Tiede:Octapharma AG: Consultancy, Investigator Other. Knaub:Octapharma AG: Employment. Oldenburg:Octapharma AG: Consultancy, Investigator Other. Bichler:Octapharma AG: Employment.