The US Food and Drug Administration (FDA) has approved eltrombopag (Promacta) for the treatment of children 6 years and older with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Eltrombopag was approved in 2008 for use in adult patients with chronic ITP.
ITP affects up to 5 in 100,000 children each year and is characterized by a low platelet count. Of those with ITP, approximately 30% experience persistent disease for more than 6 months and are diagnosed with chronic ITP. Such patients are at risk for significant bleeding.
The FDA approval is based on evidence from 2 clinical trials—the PETIT and PETIT2 studies.
PETIT and PETIT2 Clinical Trials
PETIT was a phase 2, multi-center, three-part study to investigate the efficacy, safety and tolerability of eltrombopag in pediatric patients with previously treated chronic ITP. The primary endpoint (percentage of participants who achieved a platelet count >=50 Gi/L without rescue therapy at least once between Weeks 1 and 6) was met by 63% and 18% of eltrombopag and placebo patients, respectively (P
= 0.0043). The secondary efficacy endpoint analyses demonstrated clinically meaningful benefit in terms of decreased need for rescue treatment (14% of patients on eltrombopag compared to 59% of patients on placebo).
PETIT2 was a Phase 3, multi-center, two-part study to investigate the efficacy, safety and tolerability of eltrombopag 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. The primary endpoint (percentage of participants who achieved a platelet count >=50 Gi/L without rescue therapy for at least 6 out of 8 weeks between Weeks 5 and 12) was met by 43% of patients treated with eltrombopag and 4% of patients treated with placebo (P
In both studies, safety was consistent with the known safety profile of eltrombopag in chronic ITP in adults and the population under study. The most common adverse reactions in pediatric chronic ITP patients 6 years and older were upper respiratory tract infection, nasopharyngitis and rhinitis.
ITP is a blood disorder characterized by low platelet counts that impede normal clotiting. There are 2 types of ITP—acute and chronic. Acute ITP mainly occurs in children, often after a viral infection. The platelet count returns to normal within 6 to 12 months and treatment may not be needed. However, up to 30% of teenagers and children with ITP experience persistent disease for more than 6 months and are diagnosed with chronic ITP.
The goal of treatment in chronic ITP for children is to maintain a safe platelet count that stops or prevents bleeding. According to Novartis, the most commonly available and used therapies—corticosteroids and intravenous immunoglobulin (IVIG)—are associated with side effects that are often difficult to tolerate in a pediatric setting.
In a press release, James B. Bussel, MD, a professor of pediatrics, of pediatrics in obstetrics and gynecology and of pediatrics in medicine at Weill Cornell Medical College, and lead study investigator of the PETIT study stated:
"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."
"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."
Eltrombopag is a once-daily oral thrombopoietin (TPO) receptor agonist that works by inducing stimulation and differentiation of megakaryocytes (large cells, found especially in bone marrow) from bone marrow stem cells to increase platelet production. The drug is also approved to treat patients with chronic hepatitis C virus infection as well as patients with severe aplastic anemia.
Novartis gains FDA approval for Promacta® providing new option for children, ages 6 and older, with chronic ITP, a rare blood disorder [press release]. Basel, Switzerland: Novartis Pharmaceuticals; June 11, 2015. https://www.novartis.com/news/media-releases/novartis-gains-fda-approval-promacta%C2%AE-providing-new-option-children-ages-6-and