Study Design

Asunercept (APG101) has been evaluated in a single arm phase I clinical trial for the treatment of myelodysplastic syndromes (MDS). The open-label study was conducted in two clinical centers in Germany (Heidelberg and Mannheim) and included twenty patients with low to intermediate-1 risk MDS who were transfusion dependent. Patients had to be refractory to erythropoietin-stimulating agents (ESA).

The cohort was treated with asunercept over a period of three months and followed for an additional six months. An extension of treatment was not intended. The primary objectives of the study were safety and tolerability. Secondary objectives included changes in transfusion frequency and changes in parameters involved in erythropoiesis. For detailed information regarding trial design, inclusion criteria, and participating study sites, please visit www.clinicaltrials.gov.

 

 

 

Results

In the study, treatment with asunercept was well tolerated and led to a significant decrease in transfusion frequency for more than six months (end of follow up period) in 44% of the patients. In addition, measurements of parameters involved in erythropoiesis (i.e., number and function of progenitor cells) demonstrated that APG101 could stimulate erythropoiesis in these patients.

Current Status

The phase I trial has been completed, final data will be published in late 2016. Apogenix is in preparation of phase II proof-of-concept trials to evaluate the safety and efficacy of asunercept in MDS patients using various dosing regimens of the drug candidate and, depending on study design, in combination with ESA.

 

Apogenix’ lead immuno-oncology candidate asunercept (APG101) is in clinical development for the treatment of solid tumors and malignant hematological diseases, such as myelodysplastic syndromes (MDS). MDS is a bone marrow disorder that is characterized by ineffective hematopoiesis and can lead to severe anemia. In most cases, the anemia is treated with blood transfusions that eventually result in an iron overload, which can damage the liver and other organs.

At the same time, the number of thrombocytes that are responsible for coagulation and the number of leucocytes that are responsible for immune defense are significantly decreasing. As a result, MDS patients frequently suffer from sudden bleeding and life-threatening infections. In addition, these patients are at risk for developing acute myeloid leukemia, a type of blood cancer.

 

 

 

The ineffective hematopoiesis seen in MDS patients is influenced by the CD95 system. Treatment with asunercept, which inhibits the CD95 system, directly addresses the cause of the disorder and could thus provide a cure for MDS.

Currently, there is no approved drug for the treatment of low and intermediate-1 risk MDS patients, and only few clinical trials have rendered positive results. This illustrates the significant unmet medical need in this indication.