FDA Grants Fast Track Status to Eryaspase for Hypersensitive Acute Lymphocytic Leukemia

FDA

The FDA has granted a fast track designation to eryaspase for use as a potential therapeutic option in patients with acute lymphocytic leukemia (ALL) who have developed hypersensitivity reactions to Escherichia coli–derived pegylated asparaginase.¹

Eryaspase consists of L-asparaginase encapsulated inside donor-derived red blood cells, and it was designed to target altered asparagine and glutamine metabolism in cancer cells. L-asparaginase is well established in the treatment of ALL; however, toxicity has prevented its use in patients who are particularly fragile.² The encapsulation of L-asparaginase in the red blood cells may broaden the scope of the agent to other indications.

“This is yet another significant milestone and meaningful inflection point in advancing our lead product candidate eryaspase, further supporting our recently announced intention to submit a biologics license application for eryaspase in hypersensitive [patients with] ALL,” Gil Beyen, chief executive officer of ERYTECH Pharma, stated in a press release. “We believe that the FDA’s fast track designation for eryaspase underscores its potential to address this high unmet medical need.”

In the phase 2 NOR-GRASPALL-2016 trial (NCT03267030), investigators examined the safety and pharmacological profile of eryaspase in patients with acute lymphoblastic leukemia who had experienced hypersensitivity reactions to pegylated asparaginase therapy.³

A total of 55 patients were enrolled to the trial at 21 clinical sites in the Nordic and Baltic countries of Europe. Patients received eryaspase in combination with chemotherapy every 2 weeks. The primary objectives of the research were to evaluate asparaginase enzyme activity and safety, and both end points were met.

Results indicated that the agent showcased sustained asparaginase enzyme activity that was above the threshold of greater than 100 U/L at trough levels 14 days following the first infusion in 54 of the 55 patients who received treatment.

The agent was also indicated to be well tolerated when combined with chemotherapy. All participants were able to receive the courses of asparaginase, as intended, and the median number of doses received per patient was 5. Only 2 of the patients experienced severe allergic reactions to treatment and withdrew.

“Maintaining adequate asparaginase treatment following hypersensitivity to PEG-asparaginase remains an important goal when treating patients with ALL,” Line Stensig Lynggaard, MD, study leader for the Nordic Society of Pediatric Hematology and Oncology, had stated in a prior press release. “A global shortage of supply Erwinia-derived asparaginase, which is the current alternative treatment option to PEG-asparaginase, highlights the need for new alternative treatment options. Our study has demonstrated that eryaspase, given as a convenient schedule every 2 weeks, provides a sustained asparaginase enzyme activity level, few hypersensitivity reactions, and is generally well tolerated in combination with chemotherapy.”

An ongoing phase 3 Trybeca-1 trial (NCT03665441) is also evaluating the use of eryaspase plus chemotherapy vs chemotherapy alone in the second-line treatment of patients with advanced pancreatic cancer.⁴ Enrollment has completed for this trial, and final data are anticipated to be shared in Q4 2021.

Additionally, in the ongoing phase 2/3 TRYbeCA-2 trial (NCT03674242), the safety and efficacy of eryaspase plus chemotherapy will be compared with chemotherapy alone in the first-line treatment of patients with triple-negative breast cancer.⁵

References

1. ERYTECH granted US FDA fast track designation for eryaspase in hypersensitive ALL. News release. ERYTECH Pharma. July 29, 2021. Accessed July 30, 2021. https://bit.ly/3zXvPyZ
2. Eryaspase. ERYTECH Pharma. Accessed July 30, 2021. https://bit.ly/2V9ABKN
3. ERYTECH announces positive results from eryaspase phase 2 trial in acute lymphoblastic leukemia presented at the American Society of Hematology Annual Meeting. News release. ERYTECH Pharma. December 7, 2020. Accessed July 30, 2021. https://bit.ly/3fgtQxA
4. Study of eryaspase in combination with chemotherapy versus chemotherapy alone as 2nd-line treatment in APC (Trybeca-1). ClinicalTrials.gov. Updated February 15, 2021. Accessed July 30, 2021. https://clinicaltrials.gov/ct2/show/NCT03665441
5. Study of eryaspase in combination with chemotherapy versus chemotherapy alone as 1st line treatment of TNBC (TRYbeCA-2). ClinicalTrials.gov. Updated January 21, 2021. Accessed July 30, 2021. https://clinicaltrials.gov/ct2/show/NCT03674242