Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A.

This phase 3 pivotal study evaluated the safety, efficacy, and pharmacokinetics of a recombinant FVIII Fc fusion protein (rFVIIIFc) for prophylaxis, treatment of acute bleeding, and perioperative hemostatic control in 165 previously treated males aged ≥12 years with severe hemophilia A. The study had 3 treatment arms: arm 1, individualized prophylaxis (25-65 IU/kg every 3-5 days, n = 118); arm 2, weekly prophylaxis (65 IU/kg, n = 24); and arm 3, episodic treatment (10-50 IU/kg, n = 23). A subgroup compared recombinant FVIII (rFVIII) and rFVIIIFc pharmacokinetics. End points included annualized bleeding rate (ABR), inhibitor development, and adverse events. The terminal half-life of rFVIIIFc (19.0 hours) was extended 1.5-fold vs rFVIII (12.4 hours; P < .001). Median ABRs observed in arms 1, 2, and 3 were 1.6, 3.6, and 33.6, respectively. In arm 1, the median weekly dose was 77.9 IU/kg; approximately 30% of subjects achieved a 5-day dosing interval (last 3 months on study). Across arms, 87.3% of bleeding episodes resolved with 1 injection. Adverse events were consistent with those expected in this population; no subjects developed inhibitors. rFVIIIFc was well-tolerated, had a prolonged half-life compared with rFVIII, and resulted in low ABRs when dosed prophylactically 1 to 2 times per week.

'Strange money': risk, finance and socialized debt.

This paper explores an essential but neglected aspect of recent discussions of the banking and financial system, namely money itself. Specifically, I take up a distinction drawn by Susan Strange which has never been fully elaborated: between a financial system that is global, and an international monetary system that remains largely territorial. I propose a sociological elaboration of this distinction by examining each category, 'finance' and 'money', in terms of its distinctive orientation to risk and debt. Money is distinguished by its high degree of liquidity and low degree of risk, corresponding to expectations that derive from its status as a 'claim upon society'- a form of socialized debt. But as Strange argued, these features of money are being undermined by the proliferation of sophisticated instruments of financial risk management -'strange money'- that, as monetary substitutes, both weaken states' capacity to manage money, and more broadly, contribute to 'overbanking'. The ultimate danger, according to Strange, is the 'death of money'. The paper concludes by exploring the implications of the distinction for sociological arguments about the changing nature of money.