FDA Approval for Pegaspargase
- Approved for acute lymphoblastic leukemia
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interaction and contraindications.
On July 24, 2006, the U.S. Food and Drug Administration granted approval to pegaspargase (Oncaspar®, made by Enzon Pharmaceuticals, Inc.) for the first-line treatment of patients with acute lymphoblastic leukemia (ALL) as a component of a multi-agent chemotherapy regimen. Pegaspargase was previously approved in February 1994 for the treatment of patients with ALL who were hypersensitive to native forms of L-asparaginase.
Asparaginase exerts selective antileukemia activity by depletion of serum asparagine. The current approval is based on similar sustained reductions of serum asparagine concentrations in patients receiving an pegaspargase-containing regimen compared to patients receiving a native E. coli L-asparaginase-containing regimen. Due to the longer half-life of pegaspargase, similar antileukemic activity was achieved with a single pegaspargase dose compared to six to nine doses of native E. coli asparaginase
The trial (Children’s Oncology Group Study 1962) supporting this new indication was an open label, randomized, multicenter clinical trial that enrolled 118 children (ages 1-9 years) with previously untreated, standard-risk ALL. Treatment consisted of a four-week induction phase (IP) and two eight-week delayed intensification (DI) phases.
All patients received multi-agent chemotherapy regimen consisting of intrathecal cytosine arabinoside and systemic therapy with vincristine, prednisone, and methotrexate with either native E. coli asparaginase or pegaspargase during IP and intrathecal methotrexate and systemic therapy with mercaptopurine and either native E. coli asparaginase or pegaspargase during both DI phases.
Pegaspargase was administered intramuscularly at 2,500 IU/m2 on day 3 of the four-week induction phase and on day 3 of each of two eight-week DI phases. Native E. coli L-asparaginase was administered intramuscularly at 6,000 IU/m2 three times weekly for nine doses during induction and for six doses during each DI phase.
The two study arms were balanced for most major prognostic factors; however, patients allocated to receive the native E. coli asparaginase-containing chemotherapy had a higher percentage of children ages 1-2 years (34 percent vs. 19 percent), with platelet counts <50,000 cells/µl (51 percent vs. 34 percent), and with equivocal central nervous system involvement (15 percent vs. 7 percent).
The study demonstrated similar mean asparagine concentrations between the two study arms at multiple time-points during all treatment phases. Event-free survival (time from randomization to either death, induction failure, relapse at any site, or start of new cancer treatment) was assessed in all patients. With a median follow-up of 3.2 years, the three-year event-free survival rates were approximately 80 percent in both arms.
The most serious, sometimes fatal, pegaspargase toxicities were anaphylaxis, other serious allergic reactions, thrombosis (including sagittal sinus thrombosis), pancreatitis, glucose intolerance, and coagulopathy.
The most common adverse events were allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, central nervous system thrombosis, coagulopathy, hyperbilirubinemia, and elevated transaminases.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Understanding the Approval Process for New Cancer Treatments.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.