FDA Grants Fast Track Designation to RZ-001 for Glioblastoma

The FDA has granted fast track designation to the RNA replacement enzyme–based cancer gene therapy RZ-001 for the treatment of patients with glioblastoma, according to an announcement from Rznomics Inc.¹

RZ-001 has exhibited promising outcomes in preclinical studies, demonstrating augmented anticancer efficacy and increased survival rates.

“We are proud to receive fast track designation from the FDA,” Seong-Wook Lee, PhD, MSc, chief executive officer of Rznomics, stated in a news release. “This designation signifies an important milestone in developing a safe and effective treatment for patients with glioblastoma who are in need of new therapeutic options.”

The RNA replacement enzyme–based cancer therapy is designed specifically for the treatment of patients with glioblastoma multiforme, and it selectively targets and cleaves hTERT mRNA, subsequently substituting it with the therapeutic gene RNA. This process thereby elicits anticancer activity and cytotoxic effects. This is done by trans-ligating an HSVtk-encoding sequence into the reprogrammed hTERT mRNA. Notably, glioblastoma multiforme is recognized as the most malignant tumor within the central nervous system, characterized by an elevated mortality rate and a current lack of efficacious treatment modalities.

RZ-001 will be evaluated in a phase 1/2 open-label clinical trial (NCT06102525) to investigate its safety, tolerability, immunogenicity, and preliminary clinical activity when administered in combination with valganciclovir (VGCV) in patients with hTERT-positive glioblastoma multiforme.²

The trial will be conducted in 2 parts. Part 1 of the investigation will evaluate escalating doses of the study drug to determine the maximum tolerated dose (MTD)/recommended phase 2 dose. Part 2 will entail dose expansion to assess the clinical activity associated with the optimal fixed dose determined from the outcomes of part 1.²

The primary end points of the phase 1/2 trial are the number of dose-limiting toxicities from days 1 to 28; the MTD or maximum administered dose of RZ-001 in combination with VGCV; the number of patients with treatment-related adverse effects; the number of patients with significant laboratory abnormalities; and overall survival (OS).²

Notable secondary outcomes of the study include change in VEGF serum concentration; change in anti-adenovirus antibody serum concentration; overall response rate; duration of response; progression-free survival; OS; and neurologic function assessment.

Adult patients with histologically confirmed grade 4 astrocytoma glioblastoma multiforme and confirmed hTERT-positive expression will be evaluable for the phase 1/2 study. Other inclusion criteria include an ECOG performance score of 0, 1, or 2, and a life expectancy of 3 or more months. Exclusion criteria include diagnosis of other malignant tumors within 5 years prior to RZ-001 administration; extracranial metastases of the tumor cells; or a current diagnosis or history of HIV.²

References

1. Rznomics Inc. secures fast track designation from the U.S. FDA for RZ-001. Rznomics Inc. News release. November 10, 2023. Accessed November 14, 2023. https://www.prnewswire.com/news-releases/rznomics-inc-secures-fast-track-designation-from-the-us-fda-for-rz-001-301984712.html
2. A study to evaluate the safety, tolerability and efficacy of RZ-001 with valganciclovir (VGCV) in subjects with glioblastoma. ClinicalTrials.gov. Updated October 26, 2023. Accessed November 14, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT06102525