Clinical Trials

Date: 2015-12-08

Type of information: Presentation of results at a congress

phase: 2-3

Announcement: presentation of results at the American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, USA from December 5-8, 2015

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: acute lymphoblastic leukemia (ALL)

Therapeutic area: Cancer - Oncology

Country: Belgium, France

Trial details:

• Asparaginase is a cornerstone in the treatment of acute lymphoblastic leukemia, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies (A-Abs), which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent inactivation). Graspa® improves pharmacokinetics, tolerability and maintain circulating asparaginase activity due to the protective barrier of the erythrocyte membrane. This study is run to confirm the benefit/risk profile of Graspa® at 150 IU/kg in combination with the COOPRALL regimen in adults and children patients with relapsed acute lymphoblastic leukemia, with or without known hypersensitivity to L-asparaginase. (NCT01518517)

Latest news:

• • On December 8, 2015, Erytech Pharma announced that investigators presented additional results from the pivotal Phase 2/3 clinical trial with Graspa® that add to the body of data supporting the potential benefit of Graspa® in combination with chemotherapy in the treatment of acute lymphoblastic leukemia. These results, which were presented at the 57th Annual Meeting of the American Society of Hematology (ASH) in Orlando, included an update on the clinical activity of Graspa® versus native L-asparaginase after two years of patient follow-up, a further characterization of the pharmacokinetic and pharmacodynamics properties of both products, and an analysis of the impact of neutralizing antibodies on the efficacy and safety of Graspa® versus native L-asparaginase in a randomized Phase 2/3 study in patients with relapsed or refractory ALL.
• Professor André Baruchel, Head of Pediatric Hemato-Immunology at Paris Hôpital Robert Debré (APHP) and a trial investigator, presented a poster entitled “Updated Clinical Activity of Graspa® Versus Native L-Asparaginase in Combination with COOPRALL Regimen in a Phase 3 Randomized Trial in Patients with Relapsed Acute Lymphoblastic Leukemia”. The presentation included earlier reported safety and efficacy data, with additional two-year follow-up on event-free survival (EFS) and overall survival (OS). The two-year survival data confirm the favorable trend that had been observed after one year of follow-up. Median EFS was 11.8 months in the native L-asparaginase group and has not been reached yet in the Graspa® arm after two years of follow-up. Median OS was not reached in either of the treatment arms. The main conclusion of the presentation was that the favorable efficacy and safety profile of Graspa® offers an effective alternative option for patients who have received prior asparaginase therapy.
• Dr. Xavier Thomas, hemato-oncologist at the Lyon University Hospital and a trial investigator, presented a poster entitled “Pharmacokinetic and Pharmacodynamic Characterization of Graspa® Versus Native LAsparaginase in Combination with COOPRALL Chemotherapy in a Phase 3 Randomized Trial for the Treatment of Patients with Relapsed Acute Lymphoblastic Leukemia (NCT01518517)”.
• The mean duration of asparaginase activity above the threshold of 100IU/l during the induction phase was 20.5 days ( ±: 5.2 days) in the GRASPA arm versus 9.4 days (±: 7.4 days) in the patients treated with native L-asparaginase (p<0.001). Also in patients who had experienced prior allergies to L-asparaginase, the duration of Lasparaginase was maintained for 18.6 days (±: 6.3 days). Prolonged asparaginase activity with Graspa® was  maintained across several subpopulations (age groups, risk groups, presence or absence of prior allergic reactions to asparaginase). The difference between Graspa® and native L-asparaginase was most pronounced in adults and high risk patients, where mean duration of asparaginase activity was respectively 3.2 days and 6.3 days with native L-asparaginase versus 19.3 and 20.9 with Graspa®.
• Professor Yves Bertrand, Head of the Pediatric Hematology and Oncology Institute at the Lyon University Hospital and Principal Investigator/Coordinator of the trial, presented a poster entitled “Evaluation of the Impact of the Presence of Neutralizing L-Asparaginase Antibodies on the Efficacy and Safety of Graspa® in a Phase 3 Randomized Trial Versus Native L-Asparaginase in Patients with Relapsed Acute Lymphoblastic Leukemia”. All 80 patients enrolled and treated in the Phase 2/3 study had been treated with L-asparaginase during their first line of treatment. One third of the patients had experienced prior allergic reactions to L-asparaginase. 58% of these patients had positive antibody status at baseline. Of the other two thirds of patients, about 25% had positive antibody status at baseline. GRASPA consistently demonstrated superior duration of asparaginase activity and lower hypersensitivity regardless of antibody status. Five out of seven (71%) patients with positive antibody status, treated with native L-asparaginase, developed allergic reactions versus one out of 21 (5%) of the patients with positive antibody status in the Graspa® group. Positive antibodies appeared to attenuate the clinical activity in all treatment arms. This provides additional rationale for investigating Graspa® in patients with ALL in first line setting.
• • On November 5, 2015, Erytech Pharma announced the upcoming presentation of three abstracts at the American Society of Hematology (ASH) Annual Meeting. The poster presentations include:
• - Updated Clinical Activity of GRASPA Versus Native L-Asparaginase in Combination with COOPRALL Regimen in a Phase 3 Randomized Trial in Patients with Relapsed Acute Lymphoblastic Leukemia (Abstract #3723)
• -  Pharmacokinetic and Pharmacodynamic Characterization of GRASPA Versus Native L-Asparaginase in Combination with COOPRALL Chemotherapy in a Phase 3 Randomized Trial for the Treatment of Patients with Relapsed Acute Lymphoblastic Leukemia (NCT01518517 - Abstract #2492) - Evaluation of the Impact of the Presence of Neutralizing L-Asparaginase Antibodies on the Efficacy and Safety of GRASPA in a Phase 3 Randomized Trial Versus Native L-Asparaginase in Patients with Relapsed Acute Lymphoblastic Leukemia (Abstract #3734).

Is general: Yes