Eltrombopag (Promacta) was approved by the FDA for the treatment of pediatric patients with chronic ITP, following a lack of response to additional therapies or splenectomy.
Richard Pazdur, MD
Eltrombopag (Promacta) was approved by the FDA for the treatment of pediatric patients with chronic immune thrombocytopenic purpura (ITP), following a lack of response to additional therapies or splenectomy, based on improvements in platelet counts seen throughout two clinical trials.
In the trials, eltrombopag was compared with placebo for 159 patients, ranging from ages 1 to 17, who have chronic ITP. Within the first trial, the phase II PETIT study, 62% of patients treated with eltrombopag experienced an improvement in platelet counts compared to 32% with placebo. In the second study, the phase III PETIT2 trial, platelet counts improved within 40% of patients who received eltrombopag versus only 3% with placebo.
In 2008, eltrombopag became the first oral platelet growth factor to receive approval by the FDA. The first indication was for adult patients with chronic ITP following an insufficient response to corticosteroids, immunoglobulins, or splenectomy. In June 2015, the indication was extended to children ages 6 and older with the same condition, also based on the PETIT and PETIT2 trials.
“Today’s approval of Promacta emphasizes the FDA’s commitment to fully developing treatments in areas of pediatric hematology and oncology,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement. “This new use in ages one and up builds on a recent approval for ages six years and up, and fills an unmet need for young children whose disease has progressed after use of other available treatments.”
In the phase III PETIT2 trial, 92 patients were randomized to eltrombopag (n = 63) or placebo (n = 29). Patients were stratified into 3 groups by their age, 1217 years, 6–11 years, and 1–5 years. Those 1–5 years of age received an oral suspension formulation of eltrombopag at a starting dose of 1.2 mg/kg/day or 0.8 mg/kg/day for East Asian patients. The oral suspension formulation used in this study was approved with the new indication.
According to findings published inThe Lancet,140% of those who received eltrombopag achieved at least a 50 x 109per liter improvement in platelet counts for 6 of the last 8 weeks of the study. For the difference in response between the eltrombopag arm and placebo, the odds ratio was 18.0 (95% CI, 2.3140.9;P= .0004).
For those aged 1217, the response was 39% with eltrombopag versus 10% with placebo. In the 6–11 age bracket, platelet counts improved in 42% of patients treated with eltrombopag versus 0% with placebo. With the oral suspension formulation, the response rate was 36% versus 0% for those aged 1–5.
Following the blinded portion of the study, 87 patients went on to a 24-week open-label treatment period. In this group, 80% of patients achieved platelet counts of 50â€ˆ×â€ˆ109per liter or more at least once.
In the phase II PETIT trial, 15 patients were initially randomized into an open-label dose-finding stage of the trial. These patients did not continue into the full investigation. In the double-blind portion of the trial, 67 patients were randomized to eltrombopag (n = 45) or placebo (n = 22). In the treatment arm, 16 patients were aged 1217 years, 19 were aged 6–11 years, and ten were aged 1–5 years.
According to data published in theLancet Haematology,2within weeks 1 to 6, 62% of patients in the eltrombopag arm achieved a platelet count of 50â€ˆ×â€ˆ109per liter or more at least once without rescue, compared with 32% with placebo (odds ratio, 4.31; 95% CI, 1.3913.34, P= .011).
In this study, serious adverse events (AEs) were infrequent in both groups and thrombotic events and malignancies did not occur. The most common AEs with eltrombopag versus placebo, respectively, were headache (30% vs 43%), upper respiratory tract infection (25% vs 10%), and diarrhea (16% vs 5%). Grade 3 or 4 AEs occurred in 5 (11%) patients receiving eltrombopag and four (19%) patients receiving placebo.
In the phase III study, the most common AEs with eltrombopag versus placebo, respectively, included nasopharyngitis, rhinitis, upper respiratory tract infection, and cough. Serious AEs were more frequently observed with placebo (8% with eltrombopag vs 14% with placebo).
“It’s challenging and often very emotional for parents of a baby or toddler affected by a rare condition to manage their child’s disease with limited treatment options,” Bruno Strigini, president, Novartis Oncology, said in a statement. “Today’s label expansion for Promacta provides a new disease management option for families affected by chronic ITP and highlights our commitment to providing treatments for even the youngest children with rare diseases.”
In addition to ITP, eltrombopag is approved as a treatment for patients who have severe aplastic anemia (SAA) following an insufficient response to immunosuppressive therapy. In addition to its indications for ITP and SAA, eltrombopag is approved in combination with interferon and ribavirin for patients who have chronic hepatitis Cassociated thrombocytopenia.
Following a multibillion-dollar product exchange with GlaxoSmithKline, completed in early March 2015, eltrombopag is now manufactured and developed by Novartis.