The U.S. Food and Drug Administration has approved Doptelet (avatrombopag) for the treatment of thrombocytopenia in pediatric patients one year and older with persistent or chronic immune thrombocytopenia who have had an insufficient response to a prior therapy. The approval also includes a new formulation, Doptelet Sprinkle oral granules, specifically designed for children ages one to less than six years.
Clinical Trial Results Drive Approval
The approval was based on data from the AVA-PED-301 study, a global, randomized, phase 3 trial that evaluated the efficacy, safety, and pharmacokinetics of avatrombopag in pediatric patients with immune thrombocytopenia. The study randomized patients 3:1 to receive avatrombopag or placebo administered orally once daily for 12 weeks.
The primary endpoint results demonstrated significant clinical benefit. According to the study findings, 27.8% of patients receiving Doptelet reached the main goal of durable platelet response—meaning their platelet counts stayed at or above 50 billion per liter for at least six of the last eight weeks without needing rescue medication—compared with no patients in the placebo group (P = .0077; 95% CI, 15.8–39.7).
The alternative primary endpoint showed even more pronounced results, with 81.5% of Doptelet patients achieving platelet response compared with none in the placebo group (P < .0001; 95% CI, 71.1–91.8). By day 8, 55.6% of patients on Doptelet had platelet counts of 50 billion per liter or higher without rescue treatment (95% CI, 41.4%–69.1%; P < .0001), compared with none in the placebo group (95% CI, 0.0%–16.1%).
Safety Profile and Tolerability
Doptelet was generally well tolerated in the pediatric population. The most common side effects seen in children with persistent or chronic immune thrombocytopenia were viral infections, nasopharyngitis (common cold symptoms), cough, fever, and sore throat. In the broader clinical experience with chronic immune thrombocytopenia patients, the most common adverse reactions (10% or more) included headache, fatigue, contusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, and nasopharyngitis.
Mechanism of Action and Clinical Significance
Doptelet is an orally bioavailable, small molecule thrombopoietin receptor agonist (TPO-RA) that stimulates the proliferation and differentiation of megakaryocytes from bone marrow progenitor cells, resulting in increased production of platelets. The drug does not compete with thrombopoietin for binding to the TPO receptor.
"Doptelet represents a significant advancement in the treatment of children and adolescents with persistent or chronic immune thrombocytopenia," said Dr. Rachael Grace, pediatric hematologist and director of Hematology Clinical Research at Dana-Farber/Boston Children's Cancer and Blood Disorders Center, and lead investigator of the AVA-PED-301 study. "This therapy offers simple, flexible administration because it is oral, available as a tablet and now as a new pediatric sprinkle formulation and has no food restrictions. The approval of Doptelet for pediatric immune thrombocytopenia offers families a new treatment option that can help address challenges in managing immune thrombocytopenia in pediatric patients."
Expanding Treatment Options
The approval represents an important expansion of Doptelet's therapeutic reach. The drug was initially approved in 2018 for thrombocytopenia in adults with chronic liver disease scheduled to undergo a procedure, and in 2019, the FDA approved its expanded indication for treatment of adults with chronic immune thrombocytopenia that hadn't responded satisfactorily to previous therapy.
"Since its introduction in 2019, Doptelet has been a cornerstone therapy for chronic ITP in adults," said Duane Barnes, President of Sobi North America. "This approval not only reinforces our commitment to innovation but also allows us to expand the treatment experience for patients and families by offering Doptelet in two formulations."
Disease Background
Immune thrombocytopenia is an autoimmune condition characterized by low platelet counts, leading to excessive bruising, heavier bleeding from minor cuts, blood in the urine or stool, or unusually heavy menstrual cycles. ITP occurs in 3% to 10% of children with one or more comorbidities but is often acute and resolves spontaneously. Despite efficacious treatments that lead to remission, many patients relapse after multiple lines of therapy.
