The Food and Drug Administration has approved the use of Promacta (eltrombopag) for the treatment of children age six and older with chronic immune thrombocytopenia (ITP) who had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Promacta is a once-daily oral thrombopoietin receptor agonist that works by inducing stimulation and differentiation of megakaryocytes from bone marrow stem cells to increase platelet production.
Promacta, which is marketed by Novartis, was previously approved for use in adult patients with the same condition (OT 12/25/08 issue).
"Young patients with chronic ITP who have either an insufficient response to or side effects from standard therapies have limited treatment options, making this FDA approval of eltrombopag for children six years and older particularly important," James B. Bussel, MD, Professor of Pediatrics and Pediatric Hematology/Oncology at Weill Cornell Medical College-who was the lead investigator of the PETIT (Pediatric Patients with Thrombocytopenia from Chronic Idiopathic Thrombocytopenic Purpura) study for which Promacta's approval was based on-said in a news release. "
The drug is marketed as Promacta in the U.S. and as Revolade in most other countries.
"Through the eltrombopag studies, one of which is the largest randomized trial ever performed in children with chronic ITP, we discovered that Promacta-a treatment that can be taken once daily by mouth and shown to be well tolerated-can manage this disorder and help these young patients."
The Phase II PETIT trial, a multicenter, three-part study, investigated the efficacy, safety, and tolerability of Promacta in 52 pediatric patients with previously treated chronic ITP. Part 1 was an open-label, dose-finding study; Part 2 was a double-blind, placebo-controlled study; and Part 3 was an open-label extension.
Of the patients receiving Promacta, 63 percent met the primary endpoint, which was achieving a platelet count of at least 50Gi/L without rescue therapy at least once between weeks one and six, compared with 18 percent of the patients receiving the placebo achieving that endpoint. Also, 14 percent of the patients receiving Promacta needed rescue therapy overall, compared with 59 percent of the patients receiving the placebo.
Approval was also based on data from the PETIT2 study, a multicenter, two-part study to investigate the efficacy, safety, and tolerability of the drug in pediatric patients with previously treated chronic ITP. Part 1 was randomized, double-blind, and placebo-controlled; and Part 2 was an open-label extension. There were 72 patients in the study, and 43 percent of those treated with Promacta achieved a platelet count of at least 50 Gi/L without rescue therapy for at least six out of eight weeks between week five and 12 of treatment, compared with four percent of patients treated with the placebo achieving that endpoint.
In addition, 18 percent of patients treated with Promacta needed rescue treatment during the randomized, double-blind period, compared with 22 percent of patients receiving the placebo. And, among 10 patients receiving other ITP therapy at baseline, 50 percent reduced or discontinued concomitant therapy-mainly corticosteroids-without needing rescue therapy over the randomized and Promacta-only treatment periods.
Serious side effects associated with Promacta include liver problems, abnormal liver function tests, high platelet counts, and higher risk for blood clots and new or worsened cataracts.
The most common side effects for Promacta are nausea, diarrhea, upper respiratory tract infection, vomiting, muscle aches, urinary tract infection, inflammation in the throat or mouth, abnormal liver function tests, back pain, flu-like symptoms, skin tingling, itching, and rash.
The most common side effects of Promacta in children age six and older when used to treat chronic ITP are: upper respiratory tract infections, nasopharyngitis, rhinitis, abdominal pain, cough, inflammation in the throat or mouth, toothache, abnormal liver function tests, diarrhea, rash, and vitamin D deficiency.