MILAN – Eltrombopag significantly improved platelet counts and halved bleeding events in children with chronic immune thrombocytopenia in the phase III PETIT2 study.
"It was great to see in this study that not only did we improve platelet counts, but we also significantly reduced bleeding," study author Dr. John Grainger said at the annual congress of the European Hematology Association.
Bleeding events were reduced by 50% at week 12 and by 66% at study’s end.
"Eltrombopag is a potential new treatment for children with immune thrombocytopenia," Dr. Grainger, a consultant pediatric hematologist at the Royal Manchester (England) Children’s Hospital, said during a press briefing at the meeting highlighting the results.
Patrice Wendling/Frontline Medical News
Dr. John Grainger
Immune thrombocytopenia (ITP) is a rare autoimmune disorder that affects 5 in 100,000 children and is characterized by a low platelet count, bruising, and petechiae.
Most children with ITP get better without drug intervention, but 30% will have persistent disease. Current treatments such as splenectomy and corticosteroids often fail and carry long-term risks such as infection and bone health effects, Dr. Grainger said.
Eltrombopag (Promacta/Revolade), a thrombopoietin receptor agonist, is approved in about 90 countries, including the United States, as a treatment for adult chronic ITP, and for thrombocytopenia in patients with chronic hepatitis C infection.
Eltrombopag is not approved for use in the pediatric setting, though drug maker GlaxoSmithKline will seek a pediatric chronic ITP indication shortly, according to Dr. Peter Langmuir, vice president of clinical development at GSK Oncology.
The multicenter PETIT2 study, the largest clinical trial in pediatric ITP to date, enrolled 92 children with ITP for at least 12 months who had failed at least one prior treatment and had particularly low platelet counts of less than 30 Gi/L, which increased their risk of bleeding, Dr. Grainger observed. Children were initially randomized to daily eltrombopag or placebo for 13 weeks, with all children receiving eltrombopag for 24 weeks in the second phase of the study. Dosing ranged from 12.5 mg/kg to 75 mg based on age and weight, and was titrated according to platelet response.
In all, 40% of children on eltrombopag achieved a persistent platelet response for 6-8 weeks between weeks 5 and 12, compared with 3.4% on placebo (P less than .001).
"It should be noted that the children all started on a relatively low dose of the drug, and in some children it took a considerable time to build up responses," he said. "But on average, responses were seen between 3 and 4 weeks, so it didn’t really take long to get this durable response."
Treatment with eltrombopag also allowed 61% of children to stop or reduce other ITP treatments such as steroids, Dr. Grainger said.
Four children came off study due to a lack of response, and 5 children had abnormal liver tests, but these returned to normal after treatment discontinuation.
The most common adverse events with eltrombopag were nasopharyngitis, rhinitis, cough, and respiratory tract infections. Grade 3/4 adverse events occurred in 12.7% of children on eltrombopag and 10.3% of children on placebo, and serious events in 8% and 14%.
"This is a safe drug for children to have," Dr. Grainger said.
GlaxoSmithKline sponsored the study. Dr. Grainger has received research nurse support from Baxter and honoraria for participation on advisory boards for Amgen, Baxter, and GlaxoSmithKline.