The South Korean pharmaceutical landscape has expanded with Handok's latest regulatory victory for Doptelet (avatrombopag), marking the company's second major achievement in 2024 following the recent authorization of Empaveli for paroxysmal nocturnal hemoglobinuria (PNH).
The Ministry of Food and Drug Safety (MFDS) has granted marketing approval for Doptelet in two indications: chronic immune thrombocytopenia (ITP) in adults with insufficient response to prior treatments, and thrombocytopenia in chronic liver disease (CLD) patients scheduled for invasive procedures.
Robust Clinical Evidence in ITP
Doptelet, an oral thrombopoietin receptor agonist (TPO-RA), has demonstrated compelling efficacy in clinical trials. In the pivotal phase 3 study 302, patients receiving Doptelet achieved a median cumulative platelet response of 12.4 weeks compared to 0 weeks for placebo. The drug showed rapid onset of action, with 65.6% of treated patients reaching platelet counts ≥50,000/µL within eight days of treatment initiation.
A retrospective analysis of real-world data has further strengthened Doptelet's clinical profile. Among 44 U.S. patients who switched from other TPO-RAs to Doptelet, 93% achieved platelet counts ≥50,000/µL, and 86% reached counts ≥100,000/µL. Notably, patients who previously showed inadequate response to other TPO-RAs saw their median platelet counts increase substantially from 28,000/µL to 88,000/µL after transitioning to Doptelet.
Addressing Critical Needs in CLD-Related Thrombocytopenia
The approval also addresses a significant medical need in CLD patients, where thrombocytopenia affects approximately 78% of individuals with cirrhosis. The condition often necessitates platelet transfusions before invasive procedures, creating challenges due to blood product shortages and declining transfusion efficacy.
The ADAPT-1 and ADAPT-2 phase 3 trials demonstrated Doptelet's ability to significantly reduce transfusion dependency. For patients with platelet counts <40,000/µL, only 22.9% and 34.9% required post-procedure transfusion or rescue therapy in the Doptelet groups, compared to 65.6% and 68.6% in the placebo groups. The results were even more impressive in patients with platelet counts between 40,000 and 50,000/µL, where Doptelet eliminated the need for transfusion or rescue therapy in 88.1% and 87.9% of cases.
Strategic Partnership and Future Implications
The approval represents a milestone in Handok's collaboration with SOBI, which led to the formation of their joint venture, Handok-SOBI, in April 2024. Handok CEO Kim Young-jin emphasized the significance of this approval, stating, "Doptelet's approval marks a significant step in addressing unmet needs for patients with chronic ITP and CLD-associated thrombocytopenia. We will continue strengthening our partnership with SOBI to deliver cutting-edge rare disease therapies and enhance patients' quality of life in Korea."
Doptelet's convenience as an oral medication without dietary restrictions, combined with its established safety and efficacy profile, positions it as a valuable addition to the treatment arsenal for both ITP and CLD-related thrombocytopenia in South Korea. The drug has already received approval in major markets including the United States, Europe, Australia, and Japan.
