FDA Approves Rylaze for Subsets of Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

The FDA has granted approval to asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) for use within a chemotherapy regimen to treat adult and pediatric patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma who are allergic to the E. coli-derived asparaginase products that are traditionally used.¹

The approval may serve as a solution to a global shortage of the only other FDA-approved drug for this indication, according to a press release from the developer, Jazz Pharmaceuticals. The agent was previously granted fast track and orphan drug designations for this indication, according to the FDA.^1,2

"We are excited to bring this important new treatment to patients who are in critical need, and we are grateful to FDA for the approval of Rylaze based on its established safety and efficacy profile. We are pleased Rylaze was approved before the trial is complete and are diligently working to advance additional clinical trial data. We are committed to quickly engaging with FDA to evolve the Rylaze product profile with additional dosing options and an IV route of administration," said Bruce Cozadd, chairman, and chief executive officer, Jazz Pharmaceuticals, in the press release.¹

The newly-approved agent was evaluated in a phase 2/3 single-arm, open-label, multicenter, dose confirmation study (NCT04943952) in patients with ALL and lymphoblastic leukemia who developed hypersensitivity or silent inactivation to E. Coli-derived asparaginase. A total of 102 patients were included in the study and evaluated for the achievement and maintenance of a certain level of asparaginase activity.

During the study, the recommended dosing for the agent was determined and the drug was shown to reach the target level of asparaginase activity in 94% of patients.

Adverse events (AEs) from asparaginase erwinia chrysanthemi (recombinant)-rywn occurred in more than 15% of patients. The most common AEs observed were abnormal liver tests, nausea, musculoskeletal pain, fatigue, infection, headache, pyrexia, drug hypersensitivity, febrile neutropenia, decreased appetite, stomatitis, bleeding, and hyperglycemia. One patient had a fatal reaction to the therapy, and serious AEs were observed in 55% of patients. Of the serious AEs, those observed most frequently were febrile neutropenia, dehydration, pyrexia, stomatitis, diarrhea, drug hypersensitivity, infection, nausea, and viral infection.

A 9% permanent discontinuation rate occurred as a result of AEs. Six percent of the permanent discontinuation cases were caused by hypersensitivity and 3% were caused by infection.

The study is now assessing the drug in an expansion cohort. In communication with the FDA, Jazz Pharmaceuticals submit additional data from a completed cohort of patients treated on a dosing schedule of 25mg/m² IM on Monday and Wednesday, and 50 mg/m² given on Friday. Part 2 of the study is ongoing. Additionally, the data will be presented at an upcoming medical meeting.

“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. “Today’s approval may provide a consistently sourced alternative to a pivotal component of potentially curative therapy for children and adults with this type of leukemia,” in a statement.

_References:

_{1. 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. Accessed June 30, 2021. https://bit.ly/2UM6IzG}

_{2. FDA approves component of treatment regimen for most common childhood cancer. FDA. FDA Website. June 30, 2021. Accessed June 30, 2021. https://bit.ly/3hqFvKw}