The US Food and Drug Administration (FDA) has approved Novartis' Promacta (eltrombopag) for the treatment of children six years and older with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Promacta was approved by the FDA in 2008 for use in adult patients with the same condition.
ITP is a blood disorder characterized by blood that does not clot as it should due to a low number of platelets. People who have ITP often have purple bruises or tiny red or purple dots on the skin. They also may have nosebleeds, bleeding from the gums during dental work, or other bleeding that's hard to stop. In most cases, an autoimmune response is thought to cause ITP in which a person's immune system attacks and destroys its own platelets. 5 in 100,000 children each year is characterized by a low platelet count. Pediatric patients with chronic ITP are at ongoing risk of significant bleeding.
Promacta 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 approval of Promacta was based on data from two double-blind, placebo-controlled trials, including the largest phase III clinical trial in this patient population. Treatment with Promacta significantly increased platelet counts among some pediatric patients with chronic ITP, and some patients taking concomitant ITP medications were able to reduce or discontinue their use of these medications, primarily corticosteroids. Promacta is marketed under the brand name Promacta in the US and Revolade in most countries outside the US.
PETIT was a phase II, multi-center, three-part study to investigate the efficacy, safety and tolerability of Promacta in pediatric patients with previously treated chronic ITP. Part 1 was an open label, dose finding study; Part 2 was double-blind and placebo-controlled, and Part 3 was an open-label extension. The primary endpoint, which was 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 Promacta 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 Promacta compared to 59% of patients on placebo).
PETIT2 was a phase III, multi-center, two-part study to investigate the efficacy, safety and tolerability of Promacta 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, which was percentage of participants who achieved a platelet count >=50 Gi/L without rescue therapy for at least six out of eight weeks between Weeks 5 and 12 of Part 1 of the study, was met by 43% of patients treated with Promacta and 4% of patients treated with placebo (p=0.0011). This result was consistent across the age cohorts. The secondary efficacy endpoint analyses demonstrated clinically meaningful benefit in terms of decreased need for rescue treatment (18% of patients on Promacta compared to 22% of patients on placebo),and reduction or discontinuation of baseline ITP medications (50% or 5/10 patients in the open-label phase who were receiving other ITP therapy at baseline) over the randomized and Promacta-only treatment periods.
In both studies, safety was consistent with the known safety profile of Promacta in chronic ITP in adults and the population under study. No new safety signals were detected. The common adverse reactions in pediatric chronic ITP patients six years and older (greater than or equal to 10% and greater than placebo) were upper respiratory tract infection, nasopharyngitis and rhinitis.
Separate applications were submitted to the FDA and the European Medicines Agency (EMA) earlier this year to include chronic ITP patients one year and older. These applications include chemistry, manufacturing and control (CMC) data supporting the new powder for oral suspension formulation of Promacta.
Subscribe to PharmaTutor News Alerts by Email >>
