Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Abstract

Accessibility to iron chelators including deferoxamine and deferasirox remains obscured in many developing countries. To provide an alternative, the government pharmaceutical organization of Thailand (GPO) manufactured deferiprone which has similar bioequivalent to the standard product. Seventy-three pediatric patients with severe b thalassemias, age range 3.2-19 years, were recruited to a 1-year multicenter prospective, single arm, open label, dose escalating Phase III study of deferiprone to determine its clinical efficacy and safety. Sixty-four patients (87.6%) completed the study with good compliance (>94%). Average deferiprone dose was 79.164.3 mg/kg/day. Overall, mean serum ferritin (SF) levels at 1 year were not significantly changed from baseline. However, 45% of patients (response group) had SF reduced >15% from baseline at 1 year with a median reduction of 1,065 ng ml 21 . Baseline SF was the major factor that predicts clinical efficacy; patients with baseline SF>3,500 ng ml 21 had the most significant fall of SF at 1 year. A subgroup analysis by MRI-T2* confirmed that the response group had higher baseline liver iron and deferiprone could significantly reduce liver iron overload and normalize levels of ALT at 1 year. Although, gastrointestinal irritation (20.5%) was the most common drug-related adverse events (AEs) followed by transaminitis (16.4%) and neutropenia (6.8%), all patients were well tolerated. There was no mortality and agranulocytosis found in this trial. Monotherapy of deferiprone with appropriate dose adjustment and monitoring for adverse events appeared to be an effective chelation therapy in some patients with good compliance and acceptable safety profiles. Am. J. Hematol. 88:251-260,

Combined Chelation Therapy with Daily Oral Deferiprone and Twice-Weekly Subcutaneous Infusion of Desferrioxamine in Children with β-Thalassemia: 3-Year Experience

“…Although serum ferritin alone is not the best marker to reflect the total body iron status [37], sequential measurements represent a trend of the body iron burden. A recent 1-year study by Viprakasit et al [17] on the efficacy of monotherapy with generic DFP (GPO-L-ONE) demonstrated that only 45.2% of patients responded to treatment (reducing serum ferritin >15%) and the most significant serum ferritin base response is expected among those who have the highest initial serum ferritin level. Interestingly, our current study shows that, over 3-year study period, patients with initial serum ferritin in the so-called ‘mid range' (>2,500-4,000 ng/ml) had the most significant fall in serum ferritin (final ferritin level of 874.9 ng/ml), which exceeded the decreases in the other two groups with lower or higher initial serum ferritin levels.…”

“…However, the price of this medication is unaffordable for most patients. Deferiprone (DFP), a cheaper oral iron chelator proven effective in achieving a negative iron balance in many short- and long-term clinical trials in adult patients with iron overload[3,4,5,6,7,8,9], has recently been studied for its efficacy and safety in thalassemia children receiving chelation [10,11,12,13,14,15,16,17]. To improve the efficacy of chelation treatment, the ‘iron shuttle hypothesis' [18,19] has been proposed, leading to many studies on the combined use of DFP and DFO [10,11,20,21,22,23,24,25,26,27,28,29,30].…”

Long-term safety of deferiprone treatment in children from the Mediterranean region with beta-thalassemia major: the DEEP-3 multi-center observational safety study

“…7 Serious adverse event (SAE) An AE was considered serious, if one of the following criteria were met: results in death, is life-threatening (at time of occurrence), requires or prolongs existing hospitalization, results in disability or incapacity, or results in congenital abnormality. 8 Additionally, the following important and severe medical events were always considered as serious: acute liver failure, acute renal failure, acute respiratory failure, agranulocytosis (neutrophil count less than 0.5x10 9 /L), anaphylaxis, any malignancy, aplastic anemia, elevated liver enzymes (alanine transaminase (ALT) or aspartate transaminase (AST) more than five times baseline values), liver necrosis, malignant hypertension, neutropenia (neutrophil count less than 1.5x10 9 /L), pulmonary fibrosis, pulmonary hypertension, sclerosing syndromes, seizure (only central neurological seizures), thrombocytopenia (platelet count <150x10 9 /L), torsades de pointes, toxic epidermal necrolysis, ventricular fibrillation. Severity…”

“…Similar observations have been reported before. 1,8,9 Ethnic differences may influence the occurrence of agranulocytosis as reported in Chinese children on DFP. 10 Combined therapy was not associated with a higher risk for neutropenia consistent with existing data.…”

“…5,11,12 We cannot confirm the influence of different DFP products on the occurrence of arthropathy. 8,13 Elevated transaminases were the second most frequently identified ADR to DFP. We could not find an association between the adverse reaction and HCV serostatus or SF levels, respectively.…”