Date: 2016-12-03
Type of
information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the 58th American Society of Hematology (ASH) Annual Meeting
Company: Erytech Pharma (France)
Product: Ery-asp®/Graspa® (eryaspase - L-asparaginase loaded erythrocytes)
Action
mechanism:
- enzyme. Ery-asp®/Graspa® is a new formulation of L-asparaginase encapsulated inside donor-derived red blood cells through Erytech’s proprietary ERYCAPS technology platform. The enzyme degrades asparagine, an amino acid that is essential for the tumor cells to grow and multiply, which starves and eventually kills the cancer cells.
Disease:
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On December 3, 2016, Erytech Pharma has presented preliminary data for eryaspase, also known as Ery-asp®/Graspa® at the 58th American Society of Hematology (ASH) Annual Meeting. The research was conducted at The University of Texas MD Anderson Cancer Center. Dr. Philip Lorenzi. This preclinical study shows that eryaspase, L-asparaginase encapsulated in red blood cells, has differential dual activity on its main targets, asparagine and glutamine, when compared to non-encapsulated native asparaginase .
The anticancer effect of asparaginase products is attributed to the systemic degradation of asparagine, a critical amino acid for the growth and survival of cancer cells. Asparaginase is also known to have a glutaminase effect. The degradation of glutamine has been demonstrated to be associated with clinical toxicity. The study aimed to characterize the transport and degradation of the different amino acids between the plasma and the RBC cytoplasm in the presence of L-ASP or eryaspase. Using a new bioanalytical method, MD Anderson researchers analyzed several metabolites to study differential conversion of asparagine and glutamine. In the presence of eryaspase, asparagine was rapidly and extensively converted to aspartic acid inside the RBC, whereas eryaspase displayed significantly decreased glutaminase activity as compared to L-ASP. The approximately 3.5-fold increase in selectivity for asparagine over glutamine may explain the observed decrease in frequency of adverse events in clinical trials with eryaspase compared to L-ASP. Altered target selectivity is believed to be an additional beneficial property of the encapsulation in the RBC, on top of improved half-life and decreased immunogenicity. The results also provided further evidence of the ‘bioreactor’ mode of action of eryaspase, demonstrating that the enzymatic activity is essentially happening inside the RBC.
- Dr. Lorenzi at The University of Texas MD Anderson Cancer Center, stated, “This work presents what we believe to be the first known solution to a long-standing challenge associated with measuring the pharmacodynamics of L-asparaginase products. Using a stable isotope-based correction method, we are now able to accurately determine the concentration of amino acids present at the time of sample collection. In this study, we used this method to identify reduced selectivity for glutamine as a plausible explanation for the improved toxicity profile of GRASPA over L-asparaginase that has been observed in prior clinical studies.”
Is
general: Yes
