Deferasirox: an orphan drug for chronic iron overload in non-transfusion dependent thalassemia syndromes

ABSTRACT

Introduction: Patients with non-transfusion dependent thalassemia (NTDT) are at a significant risk of developing iron overload due to increased iron absorption from the gastrointestinal tract, resulting in a host of comorbidities. Deferasirox, the only oral iron chelator approved for use in NTDT, has been evaluated in several prospective studies and clinical trials.

Areas covered: In this review, we will summarize the studies investigating the use of deferasirox in NTDT, focusing on the two largest clinical trials available thus far. THALASSA, the first prospective, randomized and placebo-controlled trial has demonstrated significant reduction in iron burden with deferasirox treatment along with a favorable side effect profile. THETIS, an ongoing clinical trial, has confirmed the findings of THALASSA and highlighted the efficacy and safety of using higher doses of deferasirox along with an earlier dose escalation protocol.

Expert opinion: Longer follow-up and continued investigations will further tailor the treatment approach to iron chelation in patients with NTDT, which will likely affect their comorbidity profile and impact their quality of life scores. Since the iron chelation treatment algorithm in NTDT relies on MRI technology, further understanding of the molecular processes governing iron overload in this population may help establish diagnostic surrogates in resource limited countries in order to guide treatment with deferasirox.

KEYWORDS:

• Deferasirox
• iron chelation
• iron overload
• non-transfusion dependent thalassemia
• NTDT

Box 1. Drug summary

Drug name: deferasirox

Phase: approved in the European Union and the United States

Indication: NTDT population aged 10 years and older with LIC ≥ 5 mg Fe/g dw and a serum ferritin > 300 µg/l

Pharmacology description/mechanism of action: deferasirox is a tridentate ligand that binds iron in its ferric form with high affinity. It is mainly metabolized through glucuronidation and undergoes biliary excretion. It is primarily eliminated via the fecal route.

Route of administration: oral

Pivotal trial(s): THALASSA (2012).[34]

THALASSA is a multinational, randomized, double blind, placebo controlled phase II trial that established the efficacy, safety, and appropriate dosing of deferasirox in the NTDT population. Based on its findings, a treatment algorithm was established.

Declaration of interest

MD Cappellini has participated in a Novartis Pharmaceuticals speakers’ bureau and A Taher has received research funding and honoraria from Novartis Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.