FDA grants Fast Track Designation to RAG-01 in NMIBC

An IND application for RAG-01 in NMIBC was accepted by the FDA earlier this year.

The FDA has granted a Fast Track Designation to RAG-01, a first-in-class small activating RNA (saRNA) therapeutic under review for the treatment of patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC).¹

The FDA’s Fast Track designation is designed to expedite the review and development of novel treatments that will fill an unmet medical need. According to Ractigen Therapeutics, the developer of the therapy, RAG-01 is the first saRNA worldwide to receive a Fast Track Designation.

"We are thrilled to receive Fast Track Designation for RAG-01, marking a significant milestone not only for our program but also for the saRNA field as a whole,” said Long-Cheng Li, MD, co-founder, president, and CEO of Ractigen Therapeutics, in the news release.¹ “This designation underscores the urgency and importance of advancing innovative therapies like RAG-01 to address critical medical needs. We remain dedicated to accelerating the development of innovative saRNA therapies to address a wide range of diseases, including cancer, genetic disorders, and chronic conditions. Through strategic collaborations and pioneering research efforts, the company aims to deliver transformative treatments that improve patient outcomes and quality of life.”

RAG-01 is an saRNA therapy that is delivered via intravesical instillation and is designed to target and activate p21, a tumor suppressor gene.

An Investigational New Drug (IND) application for RAG-01 in BCG-unresponsive NMIBC was accepted by the FDA earlier this year, in April 2024.² The approval of the IND application initiated the launch of clinical trials of the therapy in the United States.

Ractigen Therapeutics also revealed the launch of a phase 1 trial of RAG-01 in Australia earlier this year by announcing the dosing of the first patient.³ The trial was initiated in December 2023, and has successfully enrolled and dosed 3 patients in the study to date.

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.⁴

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 secures FDA Fast Track Designation for RAG-01, a first-in-class saRNA therapy. News release. Ractigen Therapeutics. Published online and accessed May 21, 2024. https://www.ractigen.com/ractigen-therapeutics-secures-fda-fast-track-designation-for-rag-01-a-first-in-class-sarna-therapy/

2. Ractigen Therapeutics announces FDA approval for RAG-01, a first-in-class saRNA therapy for BCG-unresponsive NMIBC. News release. Ractigen Therapeutics. April 26, 2024. Accessed May 21, 2024. https://www.ractigen.com/ractigen-therapeutics-announces-fda-approval-for-rag-01-a-first-in-class-sarna-therapy-for-bcg-unresponsive-nmibc/

3. Ractigen announces first patient dosed in the phase I clinical trial of RAG-01 for NMIBC. Published online April 3, 2024. Accessed May 21, 2024. https://www.ractigen.com/ractigen-announces-first-patient-dosed-in-the-phase-i-clinical-trial-of-rag-01-for-nmibc/

4. 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 May 21, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06351904