Credit: Bill Branson
Eryaspase, a product consisting of L-asparaginase encapsulated in red blood cells, may be safer and more effective than native E coli L-asparaginase, results of a phase 2/3 study suggest.
In patients with relapsed or refractory acute lymphoblastic leukemia (ALL), eryaspase given in combination with chemotherapy produced a higher complete response rate and fewer allergic reactions than native E coli L-asparaginase in combination with chemotherapy.
Eryaspase was also well-tolerated in patients who had previously experienced allergic reactions to L-asparaginase.
ERYTECH Pharma, the company developing eryaspase, recently announced these results from the GRASPIVOTALL trial.
The study included 80 children and adults with relapsed or refractory ALL, who were randomized to 1 of 3 treatment arms.
In the first 2 arms, researchers compared eryaspase to native E coli L-asparaginase, both in combination with standard chemotherapy (COOPRALL), in patients without prior allergies to L-asparaginase. In the third arm, the team evaluated eryaspase for patients who have experienced allergic reactions related to asparaginase in their first-line treatment.
The primary endpoint of the study consisted of 2 objectives: (a) superior safety, expressed as a significant reduction of the incidence of allergic reactions with eryaspase compared to native L-asparaginase, and (b) noninferior duration of asparaginase activity above the threshold of 100 IU/L during the induction phase in the nonallergic patients. Both endpoints needed to be met for the study to be considered positive.
The main secondary efficacy endpoints included complete response, minimal residual disease, event-free survival, and overall survival.
At 1 year of follow-up, both primary endpoints were met. There was a significant reduction of allergic reactions in the eryaspase arm compared to the native L-asparaginase arm—0% (0/26) and 42.9% (12/28), respectively (P<0.001).
And there was a significant increase in the duration of circulating asparaginase activity in the eryaspase arm compared to the native L-asparaginase arm. Asparaginase levels were maintained above 100 IU/L for an average of 20.5 days with up to 2 injections during the first month of treatment with eryaspase, compared to 9.2 days in the native L-asparaginase arm, with up to 8 injections of L-asparaginase (P<0.001).
In addition, the complete response rate was higher with eryaspase. At the end of the induction phase, 71.4% of patients (n=15) in the eryaspase arm had a complete response, compared to 42.3% of patients (n=11) in the native L-asparaginase arm.
Finally, the study showed that eryaspase is well-tolerated by patients with previous allergies to L-asparaginase. Two of the 26 patients with prior allergies to L-asparaginase experienced mild allergic reactions to eryaspase.
“The results of this study are an important step forward for the treatment of ALL patients that are at risk to receive L-asparaginase, which remains an important unmet medical need,” said Yves Betrand, MD, of the Institute for Pediatric Hematology and Oncology in Lyon, France.
“The virtual absence of allergic reactions, also in patients with prior allergies to L-asparaginase, is very encouraging.”
The analysis of additional secondary and exploratory endpoints for this study is ongoing. ERYTECH said results will be available later this year and are set to be presented at an upcoming scientific conference.
Based on the results of this and earlier studies of eryaspase, ERYTECH intends to submit its application for European Marketing Authorization in the first half of 2015.
The company also plans to accelerate the product’s development in ALL in the US and to launch phase 2 clinical trials in additional oncology indications with high unmet medical need. A phase 2b study of eryaspase in acute myeloid leukemia is already underway, with more than half of the patients enrolled.
