FDA accepts IND application for RAG-01 in NMIBC

The FDA has cleared an investigational new drug (IND) application for the small activating RNA therapy RAG-01 for the management of BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), announced Ractigen Therapeutics, the developer of the therapy, in a news release.¹

Earlier this month, Ractigen Therapeutics announced the launch of a phase 1 trial of RAG-01 in Australia with the dosing of the first patient.

"FDA IND approval for RAG-01 is a major achievement for Ractigen and a significant advancement for saRNA technology worldwide," said Long-Cheng Li, MD, Founder and CEO of Ractigen Therapeutics, in the news release.¹ "This first-in-class saRNA therapy harnesses the power of RNAa to target the p21 gene, offering a promising new option for patients with limited treatment choices. This approval validates the potential of RAG-01 as a leading saRNA therapy and strengthens our position as innovators in RNA-based treatments."

RAG-01 is an saRNA therapy that is delivered via intravesical instillation and is designed to target and activate p21, a tumor suppressor gene. The approval of the IND application for the therapy will initiate the launch of clinical trials in the US.

Earlier this month, Ractigen Therapeutics announced the launch of a phase 1 trial of RAG-01 in Australia with the dosing of the first patient.² To date, the trial has enrolled and dosed 3 patients in the study.

Overall, the multi-center, open-label, first-in-human, phase 1 trial (NCT06351904) of RAG-01 in Australia is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the treatment in patients with NMIBC who have failed prior BCG therapy.³

The trial is currently enrolling adults aged 18 to 75 years who have pathologically confirmed grade 2 or grade 3 NMIBC, an expected survival time of at least 6 months, and an ECOG performance status of 2 or lower. Patients are not eligible for enrollment if they received anti-tumor treatments other than transurethral resection of bladder tumor within 21 days or 5 half-lives (whichever is shorter) from when they signed their informed consent form.

All patients will receive a starting dose of RAG-01 at 30 mg, but they will be distributed into 4 dose cohorts: 30 mg, 100 mg, 300 mg, and 600 mg.

There are 2 primary outcome measures for the study. The first is safety and tolerability of RAG-01 in patients with NMIBC during the period from screening to 6 months following the initial instillation of RAG-01. Safety and tolerability will be measured through adverse events (AEs), serious AEs, and treatment emergent AEs. The other primary outcome measure is the maximum tolerated dose and/or recommended phase 2 dose of RAG-01. These will be assessed through the evaluation of any dose-limiting toxicities with 21 days of the first instillation of RAG-01.

The estimated enrollment for the trial is 15 patients, and the estimated primary completion date is June 30, 2025.

The study is being conducted through a collaboration between Ractigen Therapeutics and GenesisCare, a leading provider of cancer care services in Australia.

References

1. Ractigen Therapeutics announces FDA approval for RAG-01, a first-in-class saRNA therapy for BCG-unresponsive NMIBC. News release. Ractigen Therapeutics. Published online and accessed April 26, 2024. https://www.prnewswire.com/news-releases/ractigen-therapeutics-announces-fda-approval-for-rag-01-a-first-in-class-sarna-therapy-for-bcg-unresponsive-nmibc-302128680.html

2. Ractigen announces first patient dosed in the phase I clinical trial of RAG-01 for NMIBC. Published online April 3, 2024. Accessed April 12, 2024. https://www.prnewswire.com/news-releases/ractigen-announces-first-patient-dosed-in-the-phase-i-clinical-trial-of-rag-01-for-nmibc-302107118.html

3. A study of RAG-01 in patients with non-muscle-invasive bladder cancer (NMIBC) who have failed bacillus calmette guérin (BCG) therapy. ClinicalTrials.gov. Last updated April 16, 2024. Accessed April 26, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06351904