The EryDex System (EDS) is used to load dexamethasone sodium phosphate (DSP) into autologous erythrocytes, creating the EDS end product (EDS-EP), which is infused once per month into the patient. The EDS has been used in 204 human subjects in clinical studies and was not associated with typical corticosteroid side effects despite long-term use.
Briefly, the system entails adding DSP to autologous erythrocytes derived from 50 mL of blood that have been processed ex vivo with hypotonic saline solutions to permit osmotic opening of pores on erythrocytes and diffusion of the drug into the cells. Subsequent incubation in a hypertonic solution reseals the cells and encapsulates the DSP within the red blood cells (RBCs). The drug-loaded RBCs (EDS-EP) are infused into the subject/patient after extensive washing.
After infusion, DSP is dephosphorylated within the RBC to dexamethasone (the active principle), which passively diffuses into the plasma. This delivery system enables administering dexamethasone at stable low systemic levels over an extended period of time.
EDS is composed of device components such as a multi-use Red Cell Loader (RCL), the EryKit_01, process solutions, as well as a drug (DSP).
The EDS is currently not marketed and being developed for the treatment of Ataxia Telangiectasia (AT), a rare autosomal recessive disorder with onset in the first years of life. Most AT patients die in the second decade of life, although some individuals survive longer. Neurological degeneration is the major contributor to the severe outcome of the disease. No established therapy is currently available; treatments are symptomatic and supportive only.
Data from short-term treatment trials have suggested that betamethasone at doses of 0.03 mg/kg, but not 0.01 mg/kg, has beneficial effects on the neurological impairment of AT patients (Buoni et al., 2006; Broccoletti, 2010; Zannolli et al., 2012). However, the 0.03 mg/kg dose of betamethasone is associated with steroid side effects in these subjects, even during short-term treatment. The EDS provides the benefit of low and constant plasma delivery of dexamethasone that has not been associated with steroid side effects despite long-term use in the pediatric population (Castro et al., 2007).
In a pilot proof of concept trial (IEDAT, Chessa et al. 2014) in 22 AT patients, EDS treatment for up to 6 months led to a statistically significant improvement in the primary efficacy measure, the ICARS, which assesses key symptoms of the disease. Additional statistically significant benefits of EDS treatment were noted in measures assessing the subjects’ global health status (IGA), adaptive behavior (VABS), and ocular motility (ad hoc scale). Overall, treatment with EDS-EP was well tolerated by the patients.
After the end of the IEDAT trial, 4 patients continued to be treated with monthly EDS-EP infusions for an additional 24 months, and their clinical outcome was compared with that of 7 age-matched patients who stopped the treatment after the first 6 infusions. The protocol included serial assessment of ataxia (ICARS and VABS) and clinical and laboratory tests revealing treatment- and steroid-dependent adverse effects, if present. Patients in the extended study experienced a continuous neurologic improvement with respect to their pretreatment status, whereas controls showed a progressive neurologic deterioration (according to the natural history of the disease) after the discontinuation of the treatment. The EDS proved to be safe and well tolerated, and none of the side effects usually associated with the chronic administration of corticosteroids were observed during the entire trial (Leuzzi et al. 2015).
EryDel, has received Orphan Drug designation in the US and EU, for EDS for the treatment of AT and is about to initiate a pivotal phase III trial with EDS in AT patients.