New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study

Abstract

Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption.The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged 10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes. One hundred seventy-three patients were randomized 1:1 to DT (n 5 86) or FCT (n 5 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study.Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications. | I N T R O D U C T I O NTransfusion and iron chelation therapy can be a lifelong requirement for many patients with transfusion-dependent anemias. Compliance with iron chelation therapy can influence the frequency and severity of iron overload-related complications, 1 with demonstrated improvement in organ dysfunction and survival in patients compliant with iron chelation therapy. [2][3][4][5][6] The once-daily oral deferasirox dispersible tablet (DT) This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. variety of anemias, including thalassemia, myelodysplastic syndromes (MDS), sickle-cell disease, and other rare anemias, 9-13 and has been used in clinical practice worldwide for over a decade. Nonetheless, barriers to optimal patient acceptance of treatment still exist with deferasirox DT, including palatability, the need to take the drug in a fasting state (ie, not being able to take with food), and drug-related side effects, notably gastrointestinal (GI) tolerability. 14 An improved filmcoated tablet (FCT) formulation of deferasirox (US, Jadenu ® ; EU, Exja...

Iron overload in patients with myelodysplastic syndromes: An updated overview

“…Deferasirox was found to decrease serum ferritin, LPI, LIC, and cardiac iron concentration in addition to increasing hepcidin levels in patients with MDS despite ongoing transfusions (Table 1). 43 92 and similar safety profiles, fewer severe gastrointestinal adverse effects, higher compliance, and a greater reduction in the serum ferritin were noted with FCT compared with deferasirox (14% and 4%, respectively). In addition, FCT appears to lead to better consistent patient satisfaction as evaluated by the modified Satisfaction with Iron Chelation (SICT) instrument and palatability questionnaire.…”

“…Regular monitoring of iron status is recommended through serial ferritin levels, which is a prognostic indicator, in addition to direct imaging modalities (mainly MRI) to measure LIC. Poor compliance with parenteral deferoxamine, characterized by a short half-life, 80 has led to its replacement by the 2 oral agents deferasirox and 92 and similar safety profiles, fewer severe gastrointestinal adverse effects, higher compliance, and a greater reduction in the serum ferritin were noted with FCT compared with deferasirox (14% and 4%, respectively). Nonetheless, much is yet to be learned regarding the optimal timing of the initiation of iron chelation and the best chelator agent, as well as the duration of therapy, especially in the transplantation setting.…”

Optimising management of deferasirox therapy for patients with transfusion‐dependent thalassaemia and lower‐risk myelodysplastic syndromes

“…10 In addition, while deferasirox FCT contains the same active substance as deferasirox DT, some of the excipients (lactose and sodium lauryl sulphate) have been removed. 7 59 In ECLIPSE, clinically significant differences were seen between patients receiving deferasirox FCT and those receiving deferasirox DT in terms of patient-reported outcomes. 59 Consistently better adherence and satisfaction/preference, and consistently fewer concerns were reported with deferasirox FCT than with deferasirox DT.…”

Iron overload in myelodysplastic syndromes (MDS)

“…ICT has become more convenient with the new deferasirox formulation in the form of film-coated tablets, which are well tolerated and can be taken with or without a meal [51,52]. Anything that makes iron chelation easier to handle may help to improve patient adherence and thus carries the potential to improve survival.…”