GTC Biotherapeutics (fka GTCB)

[DewDiligence]

Randomized, Prospective Trial of rFVIIa for Secondary Prophylaxis in Hemophilia Patients With Inhibitors

[This is an indication for FVIIa that GTC has talked about pursuing because it requires a low production cost; NovoSeven is much too expensive to treat patients prophylactically.]

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17723130&...

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J Thromb Haemost. 2007 Sep;5(9):1904-13.

Konkle BA, Ebbesen LS, Erhardtsen E, Bianco RP, Lissitchkov T, Rusen L, Serban MA.

Penn Comprehensive Hemophilia Program, University of Pennsylvania.

Background: Hemophilic patients with factor VIII (FVIII) and FIX inhibitors suffer from frequent bleeding episodes and reduced quality of life.

Objectives: To evaluate whether secondary prophylaxis with activated recombinant factor VII (rFVIIa) can safely and effectively reduce bleeding frequency as compared to conventional on-demand therapy.

Methods: Thirty-eight male patients entered a 3-month pre-prophylaxis period to confirm high baseline bleeding frequency (mean >/= 4 bleeds per month). Twenty-two patients were randomized 1:1 to receive daily rFVIIa prophylaxis with either 90 or 270 mug kg(-1) for 3 months, followed by a 3-month post-prophylaxis period.

Results: Bleeding frequency was reduced by 45% and 59% during prophylaxis with 90 and 270 mug kg(-1), respectively (P < 0.0001); however, there was no significant difference detected between doses. The majority of this reduction was maintained during the post-prophylaxis period. Although all types of bleed were similarly reduced, the effect was most pronounced for spontaneous joint bleeds. Patients reported significantly fewer hospital admissions and days absent from work/school during prophylaxis as compared to the pre-prophylaxis period. No thromboembolic events were reported during prophylaxis.

Conclusion: Clinically relevant reductions in bleeding frequency during prophylaxis as compared to conventional on-demand therapy were achieved without raising safety concerns. These results provide evidence for the concept of secondary rFVIIa prophylaxis in inhibitor patients with frequent bleeds.
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