FDA Approves Promacta® for New Pediatric Chronic Immune Thrombocytopenia (cITP) Indication

Ligand Pharmaceuticals Incorporated LGND announces that the FDA has approved a supplemental New Drug Application (sNDA) for the use of Promacta® (eltrombopag), a Novartis product, for the treatment of children six years and older with chronic immune thrombocytopenia (cITP) 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 condition4. Promacta was acquired by Novartis in March 2015 from GSK. Promacta was discovered as a result of research collaboration between GSK and Ligand Pharmaceuticals and developed by GSK. ITP affects as many as 5 in 100,000 children each year2 and is characterized by a low platelet count1. Up to 30% of affected children experience persistent disease for more than 6 months and are diagnosed with cITP2,5. Pediatric patients with cITP are at ongoing risk of significant bleeding3. The approval of Promacta was based on data from two double-blind, placebo-controlled trials, including the largest Phase 3 clinical trial in this patient population. Treatment with Promacta significantly increased and sustained platelet counts among some pediatric patients with cITP, and some patients taking concomitant ITP medications were able to reduce or discontinue their use of these medications, primarily corticosteroids. Promacta should be used only in those whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. "This latest indication expansion for Promacta makes this important drug available to certain children with chronic ITP," commented John Higgins, President and Chief Executive Officer of Ligand Pharmaceuticals. "We congratulate Novartis on this accomplishment, and we are pleased with this expansion of the Promacta brand to help more patients in need." 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 production4. About the PETIT and PETIT2 Clinical Trials6 PETIT was a Phase 2, multi-center, three-part study to investigate the efficacy, safety and tolerability of Promacta in pediatric patients with previously treated cITP. 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 3 multi-center, two-part study to investigate the efficacy, safety and tolerability of Promacta in pediatric patients with previously treated cITP. 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 cITP in adults and the population under study. No new safety signals were detected. The most common adverse reactions in pediatric cITP patients six years and older (greater than or equal to 10% and greater than placebo) were upper respiratory tract infection, nasopharyngitis and rhinitis.