New Positive Clinical Results for Fitusiran in Patients with Hemophilia A and B with or without Inhibitors

New Positive Clinical Results for Fitusiran in Patients with Hemophilia A and B with or without Inhibitors

We reported new positive results from our ongoing Phase 2 open-label extension (OLE) study with fitusiran in patients with hemophilia A and B, with or without inhibitors, at the International Society of Thrombosis and Haemostasis (ISTH) Congress, held July 8 – 13, 2017 in Berlin, Germany.

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View the complete Phase 2 OLE data presentation

As of the data cutoff date, the majority of adverse events (AEs) were mild or moderate in severity, with the most common AEs consisting of transient mild injection site reactions (ISRs). There was one discontinuation due to an AE, an alanine aminotransferase (ALT) elevation in a patient with chronic hepatitis C virus (HCV) infection. Serious adverse events (SAEs) considered possibly related to drug were reported in two patients: ALT elevation in one patient with chronic HCV infection, as noted above, and seizure with confusion in one patient with a prior history of seizure disorder. Asymptomatic ALT increases >3x the upper limit of normal (ULN), without concurrent elevations in bilirubin >2x ULN, were observed in 11 patients, all of whom were hepatitis C antibody positive; at current follow-up all ALT elevations are resolved (N=10) or resolving (N=1). No thromboembolic events, laboratory evidence for pathological clot formation, or instances of anti-drug antibody (ADA) formation were reported.

Treatment with fitusiran resulted in approximately 80% lowering of antithrombin (AT) with corresponding increases in thrombin generation. Increases in thrombin generation remained within the lower end of the range of values observed in normal healthy volunteers. In an exploratory post-hoc analysis of bleeding events, a median annualized bleeding rate (ABR) of one (interquartile range [IQR]: 0-3) was achieved for all patients (N=33), and a median ABR of zero (IQR: 0-3) was achieved for the subset of patients with inhibitors (N=14), corresponding favorably to pre-study median ABR values of 20 (IQR: 4-36) in all patients and 38 (IQR: 20-48) in inhibitor patients. There was a high proportion of patients (16 of 33; 48%) who remained bleed-free in the observation period, and most patients (22 of 33; 67%) experienced zero spontaneous bleeds. All breakthrough bleed events were successfully managed with replacement factor (recombinant factor VIII or recombinant factor IX) or bypassing agents (recombinant factor VIIa or activated prothrombin complex concentrate). Patients were treated for up to 20 months in the Phase 2 OLE, with a median of 11 months on study.

We believe these data add to the growing body of evidence in support of continuing the clinical development program for fitusiran in hemophilia.


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