Replimune Group, Inc. has announced positive feedback from the U.S. Food and Drug Administration (FDA) regarding its Biologics License Application (BLA) for RP1 (vusolimogene oderparepvec) in the treatment of anti-PD1 failed melanoma. The successful pre-BLA meeting supports the company's plan to submit the BLA in the second half of 2024 under the accelerated approval pathway.
The accelerated approval pathway is based on topline results from the IGNYTE clinical trial, where RP1 combined with nivolumab demonstrated a 33% overall response rate (ORR). These findings will be further detailed at the European Society for Medical Oncology (ESMO) Annual Congress 2024, where independently reviewed data, including key secondary endpoints and subgroup analyses, will be presented.
RP1: Oncolytic Immunotherapy
RP1 (vusolimogene oderparepvec) is Replimune’s lead product candidate, derived from a proprietary strain of herpes simplex virus. It is engineered with a fusogenic protein (GALV-GP R-) and GM-CSF to maximize tumor cell death, enhance the immunogenicity of cell death, and activate a systemic anti-tumor immune response.
IGNYTE Trial Details
The IGNYTE trial is an open-label, dose-expansion study that assigned 156 patients with advanced or metastatic cutaneous melanoma to receive intratumoral RP1 combined with intravenous nivolumab. The primary endpoint of the study was safety, tolerability, and ORR per modified RECIST v1.1 criteria. Secondary endpoints included duration of response (DOR), complete response (CR) rate, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
According to a press release from Replimune Group, Inc, the median patient age was 62 years (range, 21-91), 104 (66.7%) were males, and 81 (51.9%) had stage IV M1b/c/d disease. In total, 117 (75%) patients received prior anti–PD-1 therapy outside of the adjuvant setting, 74 (47.4%) received both anti–PD-1 and anti–CTLA - 4therapy, and 17 (10.9%) received BRAF- directed therapy. Furthermore, 105 (67.3%) patients had primary resistance to prior anti–PD-1 therapy, and 50 (32.1%) had lactate dehydrogenase (LDH) greater than the upper limit of normal.
Ongoing Confirmatory Trial
Replimune is currently conducting the confirmatory IGNYTE-3 trial. This trial is crucial for securing full approval for RP1 and is designed to further evaluate the clinical benefit of RP1 in combination with nivolumab.
Management Commentary
"This successful pre-BLA meeting confirmed that the accelerated approval path is available for RP1 in anti-PD1 failed melanoma," said Sushil Patel, Ph.D., Chief Executive Officer at Replimune. "With the confirmatory IGNYTE-3 trial underway, we remain on track to submit the BLA in 2H 2024 and continue our preparations to bring RP1 to patients with advanced melanoma."
