PF499 COMPLIANCE AND CLINICAL BENEFIT OF DEFERASIROX GRANULE FORMULATION VS DISPERSIBLE TABLETS IN PEDIATRIC PATIENTS WITH TRANSFUSIONAL IRON OVERLOAD: RESULTS FROM THE PHASE II CALYPSO STUDY
Authors: Taher A.T. , Wali Y. , Cruz M.C. , Charoenkwan P. , Bachir J. , Aushev A. , Manukyants A. , Viprakasit V. 
Published: December 2023

Background:Deferasirox (DFX) dispersible tablets (DT), a once‐daily oral iron chelator, have demonstrated safety and efficacy in adult and pediatric patients (pts) with transfusional iron overload. However, barriers to optimal adherence to iron chelation therapy (ICT) remain. Film‐coated tablet (FCT) and granule formulations were developed to improve palatability, tolerability and patient compliance. Both contain the same active substance (strength adjusted to maintain comparable exposure to DT) but are lactose‐free and can be taken with a light meal. Granules (sprinkled onto soft food, eg yoghurt) are convenient for pediatric pts unable to swallow the FCT.Aims:CALYPSO (ClinicalTrials.gov ID: NCT02435212) evaluated compliance, clinical benefits and safety of DFX granules vs DT in pediatric pts with iron overload.Methods:ICT‐naïve and pre‐treated (5‐day ICT washout prior to randomization) pts aged 2–<18 yrs with transfusion‐dependent anemias, ∼20 prior pRBC transfusions and serum ferritin (SF) >1000ng/mL were enrolled. Pts were randomized 1:1 to DFX granules or DT for 48 wks, stratified by age group and prior ICT. Parents/guardians provided written informed consent. ICT‐naïve pts started on DFX DT 20 mg/kg/day or granules 14 mg/kg/day, adjusted after 4 wks as needed; pre‐treated pts received a starting dose corresponding to their closest pre‐washout dose, adjusted every 3 months as needed. The co‐primary objectives were to evaluate compliance (using stick pack/tablet count) and change from baseline in SF after 24 wks for both formulations in ICT‐naïve pts. Analyses were performed using an ANCOVA model with treatment, age group and baseline SF (for the analysis of change from baseline in SF only) as covariates. Safety was a secondary endpoint. Significant results (at a two‐sided 10% level) had to be shown for both primary endpoints for the trial to meet the primary objective.Results:224 pts, mostly with β‐thalassemia major (n = 142 [63.4%]), were randomized to granules (N = 112) or DT (N = 112). Overall, 108 pts were ICT‐naïve (median age 2.0 yrs) and 116 were ICT pre‐treated (median age 7.5 yrs). 35 pts discontinued early, most commonly (≥5%) because of adverse events (AEs; n = 4 [3.6%] vs n = 8 [7.1%] in the granules and DT arm, respectively) and withdrawal by parent/guardian (n = 4 [3.6%] vs n = 8 [7.1%]). Mean ± SD DFX dose received was 16.6 ± 4.3 and 22.8 ± 7.0 mg/kg/day in pts receiving granules and DT, respectively, with most pts receiving treatment for ≥44 wks in both arms (n = 80 [72.7%] vs n = 69 [62.2%]).Least squares mean (LSM) compliance over 24 wks in ICT‐naïve pts in the DFX granules and DT groups, respectively, was 86.8% and 84.3% (LSM difference 2.6%; two‐sided P = 0.3598); LSM change from baseline in SF was +5 and –172ng/mL (LSM difference: 176ng/mL; two‐sided P = 0.2546). Outcomes were similar in the overall and pre‐treated populations (Table).Most frequently observed AEs (≥20% in either arm) in pts receiving granules or DT, respectively, were increased urine protein/creatinine ratio (n = 26 [23.6%] vs n = 38 [34.2%]), upper respiratory tract infection (n = 29 [26.4%] vs n = 32 [28.8%]), pyrexia (n = 29 [26.4%] vs n = 26 [23.4%]), and increased alanine aminotransferase (n = 22 [20.0%] vs n = 15 [13.5%]).Summary/Conclusion:In ICT‐naïve pts, compliance with both DFX formulations was high and not significantly different. Change from baseline in SF was also not significantly different over 24 wks. Similar findings were seen in ICT pre‐treated pts. The safety profile of the granules was consistent with the general safety profile of DFX. Alternative DFX formulations may be useful for some pts.image