Chronic Immune Thrombocytopenia
The approval was based on data from a phase 3, double blind, placebo-controlled trial evaluating the efficacy of Doptelet in adult patients (N=49) with chronic immune thrombocytopenia who previously received 1 or more prior chronic immune thrombocytopenia therapies (ie, corticosteroids, immunoglobulins, azathioprine, danazol, cyclophosphamide and/or rituximab). The primary outcome measure was the cumulative number of weeks in which the platelet count was ≥50 x109/L during the 6-month treatment period in the absence of rescue therapy.
Results showed that patients treated with Doptelet had a longer duration of platelet counts ≥50 x109/L in the absence of rescue therapy compared with those who received placebo (median 12.4 [0, 25] vs [0, 2] weeks, respectively, P <.0001). In addition, a larger proportion of patients in the Doptelet arm had platelet counts ≥50 x109/L at day 8 compared with placebo (21/32; 66% vs 0/17; 0.0%, respectively; P <.0001).
Chronic Liver Disease
The approval was based on results from the ADAPT-1 (N=231) and ADAPT-2 trials (N=204), 2 identically-designed multicenter, randomized, double-blind, placebo-controlled studies. Study results showed that patients in the Doptelet treatment groups had a greater proportion of responders (defined as patients who did not require a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure) than the corresponding placebo treatment groups.
ADAPT-1
- Low baseline platelet count cohort (60mg dose): 66% vs 23%; P <.0001
- High baseline platelet count cohort (40mg dose): 88% vs 38%; P <.0001
ADAPT-2
- Low baseline platelet cohort (60mg dose): 69% vs 35%; P =.0006
- High baseline platelet cohort (40mg dose): 88% vs 33%; P <.0001
Both trials demonstrated a higher proportion of patients who achieved the target platelet count of ≥50×109/L on the day of procedure (secondary endpoint; Doptelet vs placebo):
ADAPT-1
- Low baseline platelet count cohort: 69% vs 4%; P <.0001
- High baseline platelet count cohort: 88% vs 21%; P <.0001
ADAPT-2
- Low baseline platelet cohort: 67% vs 7%; P <.0001
- High baseline platelet cohort: 93% vs 39%; P <.0001
Both trials demonstrated a greater mean change in platelet counts from baseline to the day of the procedure (secondary endpoint; Doptelet vs placebo):
ADAPT-1
- Low baseline platelet count cohort: 32x109/L vs 0.8x109/L; P <.0001
- High baseline platelet count cohort: 37.1x109 /L vs 1.0x109/L; P <.0001
ADAPT-2
- Low baseline platelet cohort: 31.3x109/L vs 3.0x109/L; P <.0001
- High baseline platelet cohort: 44.9x109 /L vs 5.9×109 /L; P <.0001
A measured increase in platelet counts was observed in both Doptelet treatment groups over time beginning on day 4 post dose, that peaked on day 10-13, decreased 7 days post-procedure, and then returned to near baseline values by day 35.