December 21, 2020 - The submission of a biologics license application to the FDA has been initiated for JZP-458 for use as a component of a multiagent chemotherapy regimen in the treatment of adult and pediatric patients with acute lymphoblastic leukemia or lymphoblastic lymphoma.
The submission of a biologics license application (BLA) to the FDA has been initiated for JZP-458 for use as a component of a multiagent chemotherapy regimen in the treatment of adult and pediatric patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) who have developed hypersensitivity or silent inactivation to E. coli–derived asparaginase.1
The application will be reviewed under the regulatory agency’s Real-Time Oncology Review pilot program, which was developed to accelerate the delivery of safe and effective treatments to patients with cancer.
“Given the urgent need for a reliable and high-quality recombinant asparaginase option for patients with hypersensitivity to E. coli–derived asparaginase, we are committed to bringing JZP-458 to market as quickly as possible and pleased to be initiating our BLA submission,” Robert Iannone, MD, MSCE, executive vice president of research and development of Jazz Pharmaceuticals, stated in a press release.
A recombinant Erwinia asparaginase, JZP-458 was developed to utilize a Pseudomonas fluorescens expression platform, according to Jazz Pharmaceuticals, the drug developer. The agent is now under examination in an ongoing phase 2/3 trial (NCT04145531), which had enrolled its first patients in December 2019.2
In the open-label, multicenter, dose confirmation and pharmacokinetic study, investigators have set out to evaluate the safety and efficacy of JZP-458 in patients with ALL or LBL who develop hypersensitivity reactions to a long-acting E. coli–derived asparaginase and have had at least 1 course of E. coli–derived asparaginase remaining in their treatment journey.3
To be eligible for participation in cohort 1 of the trial (part A or B), patients had to have previous grade 3 or higher allergic reaction to a long-acting E. coli–derived asparaginase or silent inactivation. Moreover, to be eligible for cohort 2 (part A) of the trial, they needed to have had prior grade 2 or higher allergic reaction to a long-acting E. coli–derived asparaginase or silent inactivation.
Additionally, patients had to have fully recovered from their previous allergic reaction and they had to have completed treatment with an antihistamine, epinephrine, and/or a corticosteroid before they received the study drug. Patients also needed to have acceptable liver function to be included.
Participants received 6 doses of JZP-458, which were substituted for each course of long-acting E. coli–derived asparaginase remaining. The treatment duration varied on the number of E. coli–derived asparaginase courses that remain in the patient’s original treatment plan. In part A of the trial, investigators sought to identify the dose of JZP-458 for administration and confirm the safety and efficacy of the product. In part B of the trial, investigators examined the recommended dose and schedule of the product. Patients were monitored for adverse effects and immunogenicity in both parts of the trial.
In part A, cohort 1 was comprised of evaluable patients and these patients received at least 3 doses of IM JZP-458 and a 72-hour NSAA in the second half of course 1. Then, a SDRC review was conducted based on the first 6 evaluable patients and then the first 13 evaluable patients. If they had acceptable safety and tolerability of the agent, they moved on to cohort 2 and the dose they received would be utilized in part A.
Patients in cohort 2 received at least 6 doses of IM JZP-458 on a Monday, Wednesday, and Friday dosing schedule over the course of 2 weeks. Blood samples and safety data were collected from these participants.
In part B of the trial, patients received 6 doses of intravenous JZP-458 on a Monday, Wednesday, and Friday dosing schedule over the course of 2 weeks.
The primary efficacy end point of the trial is response rate, while the primary safety end point is the safety and tolerability of IM JZP-458 as determined by treatment-emergent toxicities. A key secondary end point of the trial is the proportion of patients with the last 48-hour NSAA level of ≥0.1 IU/mL during the first course of IM JZP-458.
Jazz Pharmaceuticals announced that they are planning for a mid-2021 launch of JZP-458 after the BLA submission has been completed, the FDA has reviewed the application, and an approval is granted.