ASH Clinical News Hematology Pipeline Update: Drug Updates from the | Page 8

BLEEDING DISORDERS

Targeting Antithrombin: The Key to Achieving Hemostatic
Balance in Hemophilia Patients?
Targeting the endogenous anticoagulant antithrombin (AT)
in patients with hemophilia restored hemostatic balance and
prevented severe bleeding in people with severe forms of the
disease, according to research exploring the investigational
RNAi therapy fitusiran (formerly known as ALN-AT3).
The results of this study, which were presented at the ASH annual
meeting by lead investigator K. John Pasi, of the Royal London
Haemophilia Centre at Barts and the London School of Medicine
and Dentistry in the United Kingdom, support the hypothesis that
targeting AT improves thrombin generation and can potentially
reset patients’ hemostatic balance –providing an alternative to
factor concentrates.
“The opportunity to provide a once-monthly subcutaneous
therapy that could effectively prevent bleeding in severe hemophilia would be quite transformational for patients who would otherwise have to receive factor concentrates infusions intravenously
every other day,” Prof. Pasi told ASH Clinical News. “Put simply,
this is a massively exciting prospect.”
Fitusiran blocks the gene mutation that produces AT. “This is a
new technology harnessing RNA interference, a natural mechanism for controlling gene expression,” he explained.
In this multicenter, phase I study, Prof. Pasi and colleagues
evaluated the safety and tolerability of fitusiran in healthy volunteers and patients with moderate to severe hemophilia. The study
was designed in three parts:
• Part A, in which four healthy volunteers were randomized to
receive either 30 mcg/kg fitusiran or a placebo.
• Part B, in which 12 patients with severe hemophilia were
assigned to receive ascending doses of fitusiran (three weekly
doses of 15 mcg/kg group [n=3], 45 mcg/kg group [n=6], or
75 mcg/kg [n=3]).
• Part C, which aims to enroll several cohorts (n=3 per cohort)
and will assess a monthly dosing schedule (three doses) of
fitusiran in patients with severe hemophilia.
Enrollment has been completed in the first three cohorts, and enrollment of up to three additional cohorts is planned.
At the time of the data presentation, part A of the trial (the single
ascending dose study in healthy volunteers), had been completed, while
parts B and C are ongoing. Prof. Pasi presented results from the first 24
patients enrolled in the trial.
In part A, there were no serio