The agency’s decision was made based on data from 2 phase 3 clinical trials—ADAPT-1 and ADAPT-2—which tested the safety and efficacy of avatrombopag in 435 patients.
Avatrombopag (Doptelet, AkaRx Inc) has received a first-of-its-kind US Food and Drug Administration (FDA) approval for an indication to treat thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a medical or dental procedure.
Commonly referred to as low platelet count, thrombocytopenia has been estimated by some studies to occur in up to 76% of patients with chronic liver disease. These patients, according to Richard Pazdur, MD, the director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, are at a high risk of bleeding during procedures.
"[Avatrombopag] was demonstrated to safely increase the platelet count,” he said in a statement. “This drug may decrease or eliminate the need for platelet transfusions, which are associated with risk of infection and other adverse reactions."
The agency’s decision was made based on data from 2 phase 3 clinical trials—ADAPT-1 and ADAPT-2—which tested the safety and efficacy of avatrombopag in 435 patients with chronic liver disease and severe thrombocytopenia, all of which were scheduled to undergo a procedure that would traditionally necessitate a platelet transfusion.
The trials randomized patients with low baseline platelet counts (defined as <40 x109/L) to either 60 mg of avatrombopag or placebo, daily for 5 days, while those patients with higher platelet counts at baseline (defined as 40 to <50 x109/L) were randomized to 40 mg avatrombopag or placebo over the same timeframe.
ADAPT-1 reported 85 patients completing treatment with the 60-mg dose and 55 patients at the 40-mg dose, along with 78 receiving placebo. In ADAPT-2, 68 in the 60-mg arm, 55 in the 40-mg arm, and 68 in the placebo arms completed the trial.
Data from ADAPT-1 showed the primary endpoint—the percentage of patients who did not require any bleeding rescue up to 1-week post-procedure—was achieved by 66% of patients in the 60-mg arm compared to 23% of the controls with similar baseline counts (P <.0001), and 88% in the 40-mg arm compared to 38% receiving placebo (P <.0001). ADAPT-2 showed similar results, with 69% of the 60-mg arm meeting the primary endpoint compared to 35% of their comparative placebo cohort (P <.0006), and 88% in the 40-mg arm compared with 33% in the placebo arm (P <.0001).
The secondary endpoint of the portion of patients achieving a target platelet count of ≥50 x109/L was met by 69% and 88% of those in the 60-mg and 40-mg arms of ADAPT-1, respectively, compared to 4% and 21% of matching controls (P <.0001 for both). In ADAPT-2, the endpoint was met by 67% in the 60-mg cohort and 93% in the 40-mg group, compared with 7% and 39% in the matching control groups, respectively (P <.0001 for both).
The most common adverse events associated with avatrombopag were fever, abdominal pain, nausea, headache, fatigue, and edema in the hands or feet.