FDA Approves Component of Cancer Treatment Regimen for Patients With ALL, LBL

Asparaginase erwinia chrysanthemi (recombinant)-rywn) (Rylaze; Jazz Pharmaceuticals) provides a new alternative for a therapy in long-standing global shortage.

Officials with the FDA have approved asparaginase erwinia chrysanthemi (recombinant)-rywn) (Rylaze; Jazz Pharmaceuticals) for the treatment of acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) in pediatric patients ages 1 month and older and adults who have developed hypersensitivity to E. coli-derived asparaginase. The drug is indicated for use as a component of a multi-agent chemotherapeutic regimen.1,2

ALL occurs in approximately 5700 patients annually, about half of whom are children, and it is the most common type of pediatric cancer. An estimated 20% of patients are allergic to the standard E. coli-derived asparaginase and need an alternative their bodies can tolerate.1

According to the FDA, there has been a global shortage for years of an alternative therapy, the only other drug approved by the agency for patients with ALL or LBL with allergic reactions.1

“It is extremely disconcerting to patients, families and providers when there is a lack of access to critical drugs for treatment of a life-threatening, but often curable cancer, due to supply issues,” said Gregory Reaman, MD, associate director for pediatric oncology in the FDA’s Oncology Center of Excellence, in a press release. “[This] approval may provide a consistently sourced alternative to a pivotal component of potentially curative therapy for children and adults with this type of leukemia.”

According to Jazz Pharmaceuticals, asparaginase erwinia chrysanthemi (recombinant)-rywn) is the only recombinant erwinia asparaginase manufactured product that maintains a clinically meaningful level of asparaginase activity throughout the entire duration of treatment. The company expects this new therapy to be commercially available in mid-July.2

Asparaginase erwinia chrysanthemi (recombinant)-rywn) was granted orphan drug designation for the treatment of ALL/LBL by the FDA in June 2021. The Biologics Licensing Application (BLA) approval followed review under the Real-Time Oncology Review (RTOR) program, an initiative of FDA's Oncology Center of Excellence designed for efficient delivery of safe and effective cancer treatments to patients.1,2

"The accelerated development and approval of [asparaginase erwinia chrysanthemi (recombinant)-rywn)] marks an important step in bringing a meaningful new treatment option for many ALL patients—most of whom are children—who cannot tolerate E. coli-derived asparaginase medicine," said Dr. Luke Maese, assistant professor at the University of Utah, Primary Children's Hospital and Huntsman Cancer Institute, in a press release. "Before the approval of [this therapy]there was a significant need for an effective asparaginase medicine that would allow patients to start and complete their prescribed treatment program with confidence in supply."

According to the FDA, the efficacy of asparaginase erwinia chrysanthemi (recombinant)-rywn) was evaluated in a study of 102 patients who either had a hypersensitivity to E. coli-derived asparaginases or experienced silent inactivation. The main measurement was whether patients achieved and maintained a certain level of asparaginase activity. This study found that the recommended dosage of 25 mg/m administered intramuscularly every 48 hours would provide the target level of asparaginase activity in 94% of patients.1,2

The most common adverse effects of asparaginase erwinia chrysanthemi (recombinant)-rywn) include hypersensitivity reactions, pancreatic toxicity, blood clots, hemorrhage, and liver toxicity.1

Additional data from a Children's Oncology Group retrospective analysis of more than 8000 patients found that those who did not receive a full course of asparaginase treatment due to associated toxicity had significantly lower survival outcomes, regardless of whether those patients were high risk or standard risk, slow early responders.2

REFERENCE

1. FDA Approves Component of Treatment Regimen for Most Common Childhood Cancer [news release]. June 30, 2021; FDA. Accessed July 1, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-component-treatment-regimen-most-common-childhood-cancer

2. Jazz Pharmaceuticals Announces U.S. FDA Approval of Rylaze™ (asparaginase erwinia chrysanthemi (recombinant)-rywn) for the Treatment of Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma [news release]. June 30, 2021; Jazz Pharmaceuticals. Accessed July 1, 2021.https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval-rylazetm