Initiation of a phase I trial of SP-420, a new iron chelator for transfusion-dependent patients with MDS and MF

Iron overload (IOL) is one of the inevitable effects of chronic transfusion therapy and, thus, it is frequently detected in patients with recurrent anemia. Maintained IOL causes the deposition of ‘free’ iron into the body, particularly in the liver, heart, and endocrine glands, leading to chronic fatigue, cardiac failure, liver dysfunction, vascular damage, and a higher risk of infections.¹

Transfusional IOL is often detected in patients with β-thalassemia, sickle cell disease, myelodysplastic syndromes (MDS), myelofibrosis (MF), and other rare anemias. Transfusion-dependent patients show shortened survival outcomes that might worsen due to IOL dose-dependent complications. The current management of IOL in those patients is early detection and treatment with an iron chelator, such as deferoxamine, deferasirox, or deferiprone. In the particular case of patients with MDS, it is recommended to start chelation therapy before allogeneic transplantation. However, there is a need for safer, better-tolerated iron chelators with improved adherence to be evaluated in large prospective clinical trials.^1,2

In February 2021, it was announced that a phase I trial evaluating a new iron chelator, SP-420, will start enrolling patients with transfusional IOL due to underlying MDS or MF (NCT04741542). SP-420 is an analog of deferitrin and belongs to a family of novel orally available iron chelators named the desferrithiocin class, which have shown targeted efficacy on affected organs and are well tolerated.^2–4

The phase I, dose-escalation study will recruit patients with transfusional IOL that are diagnosed with⁴:

• MDS in a Revised International Prognostic Scoring System (IPSS-R) risk group of intermediate, high, or very high;
• or MF in a Dynamic International Prognostic Scoring System-Plus (DIPSS-Plus) risk category of intermediate-1, intermediate-2, or high risk.

Further inclusion criteria include⁴:

• deemed not eligible for other iron chelation therapy;
• and received ten or more units of packed red blood cells in the preceding 24 months and remained red cell transfusion-dependent.