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t the 2017 Congress of the International Society on Thrombosis and Haemostasis ( ISTH ), experts in non-malignant hematology gathered in Berlin , Germany , to discuss this year ’ s meeting ’ s theme , “ Transcending Scientific Boundaries .” Researchers , clinicians , and other healthcare professionals shared the latest advances in the scientific understanding of thrombotic and bleeding disorders . Here , we present highlights from the 2017 ISTH Congress , including revolutionary approaches to treating hemophilia .
The investigational RNA interference therapy fitusiran lowered levels of antithrombin in patients with hemophilia A or B with or without inhibitors , leading to improved thrombin generation , according to interim results from a phase II extension study presented at the 2017 Congress of the International Society on Thrombosis and Haemostasis .
The findings appeared to confirm results from a phase I , dose-escalation study of fitusiran in patients with hemophilia with or without inhibitors , noted the authors , led by K . John Pasi , MBChB , PhD , from Barts and the London School of Medicine and Dentistry in the United Kingdom .
In the phase I study , 30 patients with moderate or severe hemophilia A or B without inhibitors received three subcutaneous injections of fitusiran administered either once-weekly ( at doses of 0.015 , 0.045 , or 0.075 mg / kg ) or once-monthly ( at doses of 0.225 , 0.45 , 0.9 , or 1.8 mg / kg or a fixed dose of 80 mg ), and 16 patients with inhibitors received three subcutaneous injections of fitusiran 50 or 80 mg once-monthly . Patients who received the oncemonthly treatment experienced an average , dose-dependent maximum antithrombin reduction of 70 percent to 89 percent from baseline . Based on those results , the researchers selected once-monthly , fixed doses of fitusiran 50 and 80 mg for the phase II extension study .
The phase II study included 33 patients ( age range = 19-61 years ) – 14 patients with inhibitors ( 3 patients at
Attendees gather for the 2017 ISTH Congress in Berlin , Germany .
RNA Interference Therapy Fitusiran Improves Thrombin Generation in Patients With Hemophilia
the 50 mg dose and 11 at the 80 mg dose ) and 19 without inhibitors ( 10 patients at the 50 mg dose and 9 at the 80 mg dose ) – who were previously treated in the phase I study .
Patients were treated for a median of 11 months ( range = 0-20 months ). Five patients discontinued treatment : four because of withdrawal of consent and one because of asymptomatic aspartate and alanine aminotransferase ( ALT ) elevation in a patient with chronic hepatitis C infection .
During follow-up , 23 patients ( 70 %) experienced an adverse event ( AE ). The majority of AEs were mild or moderate and unrelated to fitusiran ; however , six patients reported serious AEs , two of which were deemed possibly related to fitusiran . The most common AEs included injection-site reactions ( n = 6 ; 18 %), abdominal pain ( n = 3 ; 9 %), diarrhea ( n = 3 ; 9 %), and headache ( n = 3 ; 9 %).
Eleven patients experienced ALT increases three times the upper limit of normal . Ten of those cases resolved during study follow-up , eight without dose interruptions . The authors also noted that all of those patients were hepatitis C virus – antibody positive .
No thromboembolic events occurred during the study , and there was “ no clinical or laboratory evidence of pathologic clot formation ,” the researchers reported . There were also no instances of drug-induced inhibitor formation .
At a median of 13 months ( range = 2-19 months ) after first fitusiran dose , patients at both dose levels experienced
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