Efficacy was superior to placebo regardless of patient BMI, supporting adequacy of recommended dosing regimens for overweight and obese patients.
Stuart Gordon, MD
New data suggests that among patients with chronic liver disease (CLD) and thrombocytopenia, avatrombopag (Doptelet, Dova Pharmaceuticals) is superior to placebo in increasing platelet count (PC) and reducing both the proportion of patients requiring a platelet transfusion or rescue procedure for bleeding, and the proportion of patients achieving a PC ≥50x109/L by procedure day, regardless of a patient’s body mass index (BMI).
In the poster, which was presented at the American College of Gastroenterology (ACG) meeting in Philadelphia, PA, efficacy associated with the primary endpoint was generally similar regardless of BMI category in both patient cohorts who took avatrombopag, and similarly superior to placebo in meeting the secondary endpoint: the proportion of patients achieving a PC ≥50x109/L by procedure day (Cohort 1: P <.0001; Cohort 2: P <.0001), regardless of BMI.
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“The lack of effect of BMI on avatrombopag’s efficacy is important because it speaks to consistency of effect in the chronic liver disease patient,” said Stuart Gordon, MD, professor of medicine and director of hepatology at the Henry Ford Health System in Detroit, MI. “Such data provides reassurance that dosing need not be changed according to patient weight. Additionally, as more patients present with non-alcoholic steatohepatitis liver disease, which is often associated with obesity or higher BMIs, consistent effect of avatrombopag across different body weights may be relevant.”
Results compound previous evidence from 2 phase 3 trials, suggesting avatrombopag’s superiority to placebo in reducing the need for platelet transfusions or rescue procedures for bleeding in patients with thrombocytopenia and chronic liver disease (CLD) under a scheduled procedure.
To arrive at their results, Gordon and colleagues conducted 2 randomized, double-blind, placebo-controlled phase 3 trials for avatrombopag that enrolled 435 adults with CLD and PC counts <50x109/L undergoing a procedure. Patients were divided by baseline PC into Cohort 1 (PC <40x109/L) and Cohort 2 (PC 40 to <50x109/L), and randomized 2:1 to once-daily oral avatrombopag (60 mg or 40 mg, respectively) or placebo for 5 days, with the procedure done 5 to 8 days after the last dose.
Avatrombopag was superior to placebo in both cohorts in the proportion of patients not requiring platelet transfusion or bleeding rescue (Cohort 1: P <.0001; Cohort 2: P <.0001). Efficacy associated with the primary endpoint was generally similar regardless of BMI category in both cohorts. Similarly, avatrombopag was also superior to placebo in both cohorts in the proportion of patients achieving a PC ≥50x109/L by Procedure Day (Cohort 1: P < .0001; Cohort 2: P <.0001). Efficacy associated with this secondary endpoint was again similar across the various BMI categories in each cohort.
“Given that previous options for thrombocytopenic cirrhosis patients undergoing procedures were either A) doing nothing to address the condition (with risk of bleeding) or B) administering a platelet transfusion (with its logistic difficulties and associated risks), avatrombopag provides an effective and oral medication option with a safety profile similar to that of placebo. The data in this poster should give physicians who manage patients with chronic liver disease confidence that this agent should prove effective in a number of settings,” Gordon told MD Magazine in an email.
In May, avatrombopag received first-of-its-kind approval from the US Food and Drug Administration for its indication to treat thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a medical or dental procedure.
The most common adverse events associated with avatrombopag were fever, abdominal pain, nausea, headache, fatigue, and edema in the hands or feet.