Date: 2015-06-01
Type of
information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Erytech (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: acute lymphoblastic leukemia
Therapeutic
area: Cancer - Oncology
Country: France, Belgium, Spain
Trial
details:
- The study has involved 58 investigator sites in France, Belgium and Spain. It was launched in 2009 as a Phase II/III study with an adaptive design protocol.
- The GRASPIVOTALL study is a controlled, multicenter Phase II/III trial with 80 children and adults suffering from relapsing or refractory Acute Lymphoblastic Leukemia (ALL) with three arms. The first two arms compare Graspa® to native E. Coli L-asparaginase, both in combination with standard chemotherapy (COOPRALL), in a 1-to-1 randomization in patients without prior allergies to L-asparaginase. The third arm is an open label assessment of Graspa® for patients who have experienced allergic reactions related to asparaginase in their first line treatment.
The primary endpoint of the study consisted of two objectives, in accordance with CHMP1 advice: a) superior safety, expressed as a significant reduction of the incidence of allergic reactions with GRASPA® compared to the control group, and b) non-inferior duration of asparaginase activity above the threshold of 100 IU/l during the induction phase in the non-allergic patients. Both endpoints needed to be met for the study to be considered positive. The main secondary efficacy endpoints included the assessment of clinical parameters such as complete remission (CR), minimal residual disease (MRD), event-free survival (EFS) and overall survival (OS). (NCT01518517)
Latest
news:
- • On June 1, 2015, Erytech Pharma reported complete Phase III results of its pivotal program with GRASPA® in Acute Lymphoblastic Leukemia (ALL) at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO). Prof. Dr. Yves Bertrand, oncologist at the Institute for Pediatric Hematology and Oncology in Lyon, France, presented full Phase III results of the GRASPIVOTALL trial. The title of his presentation was: Clinical activity of ERY001 (erythrocyte encapsulated l-asparaginase) and native l-asparaginase (L-ASP) in combination with COOPRALL regimen in Phase III randomized trial in patients with relapsed acute lymphoblastic leukemia (ALL) (Abstract 7004). The main conclusions of the study, as presented by Prof. Bertrand, are:
- GRASPA in combination with chemotherapy demonstrated sustained asparaginase activity, which was superior compared to L-ASP, for the treatment of patients with ALL. Duration of asparaginase activity above 100 IU/l was 20.5 days in the GRASPA group versus 9.4 days in the L-ASP control arm (p<0.001).
- GRASPA demonstrated a significantly lower risk of hypersensitivity reactions, compared to L-ASP. No hypersensitivity reactions of any grade were observed in the GRASPA treatment arm, versus 46% in the L-ASP control arm (p<0.001). The prolonged asparaginase activity was associated with improvement in Complete Remission (CR) rate. 65% of patients in the GRASPA arm were in CR after the induction phase versus 39% in the control arm (p=0.026). Treatment was generally well tolerated, with a lower risk of key events, such as coagulation disorders (35% versus 82%[1]), pancreatic toxicities (27% versus 50%1) and hepatic toxicities (19% versus 43%1).
- • On December 8, 2014, Erytech reported additional positive Phase III results from the pivotal study with ERY-ASP/GRASPA® in acute lymphoblastic leukemia. Positive top-line data of the study were made available end of September, and demonstrated that the Phase III GRASPIVOTALL clinical trial met both of its primary endpoints. A significant reduction of clinical hypersensitivity was observed with ERY-ASP/GRASPA® while maintaining asparaginase activity longer than with native L-asparaginase in the control arm. The study also showed favorable results in patients with prior allergies to asparaginase, both in terms of hypersensitivities and asparaginase activity. Additional study results based on the pre-specified key secondary endpoints were presented and discussed at an investigator meeting in connection with the annual meeting of the American Society of Hematology (ASH) in San Francisco. These additional results show:
- - a significantly improved complete remission (CR) rate and a trend towards increased overall and eventfree survival (OS and EFS) with ERY001 compared to native L-asparaginase (L-ASP). Median OS and EFS have not been reached;
- - a better overall safety profile, notably with improved clotting parameters (coagulation disorders), in addition to lower hypersensitivity reactions (no allergic reactions with ERY001 versus 43% with L-ASP, with 25% Grade 3 or above);
- - neither the risk status nor the age of the patients (children versus adults) had an influence on the study outcome;
- - favorable results also in the patients with prior hypersensitivities to asparaginase (exploratory ‘HypSen’ arm) who could not be randomized to native asparaginase.
- The most common adverse events of key interest in the two randomised arms over the one year follow-up period, regardless of relationship to study drug or grade, were as follows: elevated alanine aminotransferase: 54% versus 32%; elevated aspartate aminotransferase: 31% versus 21%; elevated bilirubin levels: 8% versus 29%; hypofibrinogenaemia: 31% versus 68%; hypoalbuminemia: 19% versus 39%; decreased antithrombin III 15% versus 71%; and: elevated amylase: 31% versus 29%; elevated lipase: 27% versus 36%, in ERY001 and L-ASP groups, respectively.
- • On September 30, 2014, Erytech reported positive Phase III results from its pivotal study with Graspa® in acute lymphoblastic leukemia. Analysis of the primary and first secondary efficacy endpoints of the GRASPALL clinical trial with one year follow up shows that the GRASPIVOTALL (GRASPALL2009-06) clinical trial convincingly meets both of its primary endpoints, and that the secondary efficacy endpoints analyzed so far confirm the favorable clinical efficacy profile of Graspa®. The study also shows favorable results in patients with prior allergies to L-asparaginase.
- Primary endpoints met:
- • Statistically significant reduction of allergic reactions: none of the 26 patients in the Graspa® arm experienced an allergic reaction versus 12 of the 28 (42.9%) patients treated with reference L-asparaginase in the control group (p<001).
- • Statistically significant increase in duration of circulating asparaginase activity: in the Graspa® group, 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 (induction phase) versus 9.2 days in the control group with up to 8 injections of reference L-asparaginase (p<001).
- Secondary endpoints confirm the favorable clinical efficacy of Graspa®
• At the end of the induction phase, 15 patients (71.4%) in the Graspa® arm show complete remission versus 11 patients (42.3%) in the control arm.
Graspa® well tolerated by patients with previous allergies to L-asparaginase
• A favorable clinical profile was seen in patients with prior allergies to L-asparaginase with only 2 patients experiencing mild allergic reactions.
These results confirm earlier observations with GRASPA® in a Phase I/II randomized dose escalation study in 24 relapsing ALL patients, and a Phase II study in first line ALL patients over 55 years of age.
Further analysis of additional secondary and exploratory endpoints is ongoing. Results will be available later this year and are planned to be presented at an upcoming scientific conference.
Based on the results of the GRASPALL study and the earlier studies performed with Graspa®, Erytech intends to submit its application dossier for European Marketing Authorization in the first half of 2015.
- • On September 10, 2013, Erytech, has announced the completion of the enrollment of patients in its pivotal Phase III study in acute lymphoblastic leukemia. The study compares Graspa®, to native asparaginase in a randomized controlled and multicenter clinical trial on 80 children and adults suffering from relapsing or refractory acute lymphoblastic leukemia. During the first quarter of this year an independent Data Safety Monitoring Board reviewed the data of the first 60 patients and recommended the transition to Phase III and the continuation of the study without changes to the protocol. Full results of this pivotal study are expected in Q3 of 2014.
- Graspa® has already successfully completed a Phase I/II study in relapsing children and adults and a Phase II study in newly diagnosed ALL patients over 55 years old. Both studies have demonstrated an improved safety profile and promising efficacy data. Earlier this year, the product also received FDA clearance to start clinical development in acute lymphoblastic leukemia in the US. The company expects to begin the enrollment of patients in the Phase Ib study in the coming months.
Is
general: Yes
