FDA Grants Orphan Drug Status to Erwinaze for Treatment of Acute Lymphoblastic Leukemia

The FDA granted orphan drug approval to Erwinaze (asparaginase Erwinia chrysanthemi) to treat acute lymphoblastic leukemia (ALL) in patients who have developed hypersensitivity to the 2 already-approved E. coli-derived asparaginase agents: Elspar (asparaginase injection) and Oncaspar (pegaspargase).

Erwinaze is indicated as a multiagent chemotherapeutic regimen and is given as an intramuscular injection 3 times a week. The drug prevents the growth of leukemia cells by limiting asparagine, a normally occurring amino acid. Neoplastic ALL cells depend on asparagine for proliferation. The enzyme L-asparaginase, an active agent in Erwinaze, lowers the circulating asparagine levels in the bloodstream; this creates an antineoplastic effect that results in the death of the ALL cells.

The approval of Erwinaze was based on 2 clinical trials that investigated the drug’s safety and efficacy. The first trial, labeled Study 1, was a single-arm, multicenter, open-label, safety and clinical pharmacology trial. It investigated 58 ALL patients with a median age of 10 years; 50% of the patients in the trial achieved asparagine levels that predict clinical efficacy (asparagine <0.4 mcg/mL or 3 μM).

“The approval of Erwinaze underscores the FDA’s commitment to the approval of drugs for conditions with limited patient populations with unmet medical needs using novel trial endpoints” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

Safety data was compiled from Study 1 and the Erwinaze Master Treatment Protocol (EMTP), which enrolled 574 patients with a median age of 9 years. The most common nonhematologic and noninfectious adverse events, which occurred in 17% of patients, were anaphylaxis, hypersensitivity, and urticaria. Grade 3/4 allergic reactions occurred in 9% of the patients in Study 1 and in 5% of the patients in the EMTP.

The drug received a contraindication for any patients with hypersensitivity to Erwinaze or who had experienced pancreatitis, thrombosis, or hemorrhage while receiving prior L-asparaginase therapy.

EUSA Pharma (USA) of Langhorne, Pennsylvania, will manufacture Erwinaze.