The first few subjects who consented

did so in the full knowledge that the dose they would receive was not likely to give Roxadustat cell line them any benefit and that they would not be able to have an additional dose of the same vector as their immune system would then reject any subsequent vector particles. Nevertheless, two of our patients, who were motivated purely by altruistic desire to help the progress of treatment for their condition, volunteered and so received the low-dose treatment. The first subject had no adverse reaction acutely to the infusion and his factor IX level stabilized at 2%. Consequently, for the last 2 years since the vector infusion, he has been able to stop prophylaxis and only treats himself for accidental injuries (Fig. 1). The second subject, treated with the low dose, 2 × 1011

vector genomes/kilogram body weight (vg/kg), also achieved a stable baseline of 2%, but due to his much more EGFR inhibitor severe pre-existing joint damage has needed to continue on prophylaxis, albeit with decreased frequency of dosing (Fig. 2). As both subjects had attained levels of less than 3% the next two subjects were treated at the intermediate dose level of 6 × 1011 vg/kg. Subject 3 attained a stable base line of 2% but also due to pre-existing joint damage has needed to continue prophylaxis but at greatly increased intervals of up to 3 weeks, compared to twice weekly before gene therapy. Subject 4 attained a base line level of 3%, which has persisted for 15 months such that he has needed no factor infusion for a year. Earlier treatments were for accidental injury provoked bleeding (Fig. 3). As neither of the subjects had achieved a base line level above 3% the next two subjects were treated at the highest dose level of 2 × 1012 vg/kg. Subject 5’s course is shown in Fig. 4. Having stabilized in the factor IX range of 5–7% a sharp rise in the liver marker enzyme, ALT, to over 10 times baseline occurred, concomitant with a fall of

the factor IX level to 3%. A course of Prednisolone starting at 60 mg/day and rapidly tapering over 6 weeks was given. ALT fell rapidly to baseline and factor IX levels rose to 6%. However, over the following months his baseline level has fallen to stabilize at 2%. The subject has not needed prophylaxis for 上海皓元医药股份有限公司 15 months since gene vector infusion but has occasional trauma provoked bleeding for which he treats himself with replacement therapy on demand. Because the rise in transaminase level occurred in subject 5 after 6 weeks the next subject had already been treated at the same dose level. His course is shown in Fig. 5. Following vector infusion the subject’s factor IX level rose to 8–10%. At 8 weeks, a slight rise in liver enzymes was noted and when the factor IX level fell to 3% he was started on a short course of Prednisolone.