Study Finds Clinical Benefit for ERY001 in ALL

Asparaginase is a commonly prescribed treatment option for acute lymphocytic leukemia (ALL), but its use can be limited by its toxicities, including drug hypersensitivity. A recent study found that the investigational drug ERY001 improved pharmacokinetics, improved tolerability, and maintained circulating aspariginase activity in relapsed ALL patients.

The results, presented by Yves Bertrand, MD, from the Pediatric Hematology Department, IHOP and Claude Bernard University, in Lyon, France, may give hope to ALL patients who need an alternative to asparaginase.

ERY001 (red blood cell–encapsulated L-asparaginase [L-ASP]) is designed to overcome the difficulties of allergic reactions. In some cases, patients’ immune systems will produce anti-asparaginase antibodies, which can lead to allergic reactions on re-exposure of the drug; some patients may also experience silent inactivation, meaning the immune system develops asparaginase-targeting antibodies in the absence of a clinical allergy. The encapsulation enables L-ASP to destroy asparagine inside the erythrocyte to prevent allergic reactions and reduce other adverse events associated with asparaginase.

This open, randomized, international, phase III study included 80 patients with relapsed ALL, ranging in age from 1 to 55 years. Patients with no known allergy were randomized to receive ERY001 (150 IU/kg; n=26) or L-ASP (10,000 IU/m2; n=28). Twenty-six patients with a prior asparaginase allergy were enrolled in an exploratory arm and received only ERY001.

In terms of the study’s two primary endpoints (duration of asparaginase >100 IU/L and the incidence of asparaginase hypersensitivity during induction):

  • ERY001 prolonged asparaginase activity >100 IU/L compared with patients in the L-ASP group (21 days vs. 9 days, respectively; p<0.001).
  • ERY001 significantly reduced the incidence of asparaginase hypersensitivity in patients without prior allergy, compared with patients with an allergy (0% vs. 43%, respectively; p<0.001).

The improved pharmacokinetics were likely due to the protective barrier of the erythrocyte membrane, Dr. Bertrand and co-investigators explained.

Secondary endpoints of the study were complete remission (CR), minimal residual disease (MRD), event-free survival, and overall survival. ERY001 led to a “slightly better” rate of CR (65% [95% CI 51.6-89.8] vs. 39% in the L-ASP group [95% CI 23.3-63.1; p=0.026]), Dr. Bertrand said during his presentation. While patients receiving ERY001 had greater event-free survival rates (65% vs. 49%), rates of one-year survival were no different between the two groups.

ERY001 was associated with less frequent coagulation (35% vs. 82%), pancreatic (27% vs. 50%), and hepatic events (19% vs. 43%), compared with L-ASP.

“The favorable efficacy and safety profile of ERY001 offers an effective alternative option for patients who have received prior asparaginase therapy with complications,” Dr. Bertrand concluded. “ERY001 provides a promising, well-tolerated, and efficacious alternative to asparaginase in patients with relapsed ALL.”


Reference

Bertrand Y, Baruchel A, Thomas XG, et al. Clinical activity of ERY001 (erythrocyte encapsulated l-asparaginase) and native l-asparaginase (L-ASP) in combination with COOPRALL regimen in phase II randomized trial with patients with relapsed acute lymphoblastic leukemia (ALL). Abstract #7004. Presented at the 2015 American Society of Clinical Oncology Annual Meeting, Chicago, IL, May 30, 2015.

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