Pivotal phase 3 findings for ofra-vec in patients with ovarian cancer are anticipated in the second half of 2022.
The FDA has granted a Fast Track Designation to ofra-vec (ofranergene obadenovec; VB-111) in combination with paclitaxel as a potential treatment for patients with platinum-resistant ovarian cancer, according to a statement from VBL Therapeutics, the company developing the gene therapy.1
Ofra-vec is currently being examined in the phase 3 OVAL study (NCT03398655), which completed enrollment in March 2022. The study contains 409 patients with recurrent platinum-resistant ovarian cancer from the United States, Europe, Israel, and Japan. The study has dual primary end points of progression-free survival and overall survival, and the company anticipates initial data in the second half of 2022.
“We are pleased to receive FDA Fast Track designation for ofra-vec in platinum-resistant ovarian cancer. The Fast Track designation can facilitate the process towards potential registration and, importantly, may help expedite the time to market for ofra-vec, if approved,” Dror Harats, MD, chief executive officer of VBL Therapeutics, said in a statement. “The readout of the progression-free survival primary endpoint in the OVAL trial will be an important milestone for VBL in the second half of this year. We believe that, if positive, this will support a Biologics License Application submission to the FDA.”
Ofra-vec is manufactured using a replication deficient adenovirus 5 to have a dual mechanism of action. The first is a partially artificial angiogenesis promoter labeled PPR-1-3X, which targets endothelial cells within angiogenic blood vessels. Once the endothelial cells are targeted, they are killed by a TNF/FAS chimera death receptor transgene, cutting off the blood supply to the tumor. In addition to the release of neoantigens from tumor necrosis, the utilization of a viral vector further draws the immune system to the tumor, resulting in further anti-tumor response, VBL theorizes.
In the phase 3 OVAL trial, women with recurrent, platinum-resistant ovarian cancer were randomized to receive paclitaxel in combination with either ofra-vec or placebo. In addition to the dual primary end points, secondary outcome measures include objective response rate and response by CA-125 levels.
Findings from a prespecified interim analysis of the first 60 patients with ovarian cancer enrolled in the OVAL study were published in the journal Gynecologic Oncology in early 2021.2 Additionally, the study has passed various safety inspections by an independent data safety monitoring committee. The most recent was completed in December 2021, based on 370 enrolled patients.
For data from the initial 60 patients that were published in Gynecologic Oncology, the median age was 62 years and most had high-grade serous cancer (97%). The median number of prior therapies was 3 and 43% had received a prior PARP inhibitor.
At this assessment, ofra-vec plus paclitaxel demonstrated at least a 10% advantage over placebo plus paclitaxel, which passed the criterion set forth for the interim futility analysis. The blinded results showed that 53% of patients experienced a CA-125 response, with 15% having a complete remission. The authors deduced this would equate to an estimated response rate of 58% with ofra-vec.
“The goal of this interim analysis was to get a signal of drug activity, using CA-125 as a validated biomarker,” study investigator Bradley J. Monk, MD, FACOG, FACS, Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine, said when the findings were published. “The intention was to reduce the risk of a negative trial and increase the chance of success. New and novel approaches that have the potential to significantly extend progression free survival or survival are eminently required in platinum-resistant ovarian cancer. VB-111, with its very unique mechanism of action, could be one of those novel approaches and I look forward to the progress of the OVAL trial, which is well designed to test this hypothesis.”
The Fast Track Designation is meant to facilitate and expedite the development of treatments for serious conditions that fill an unmet need. With this new designation, VBL Therapeutics will benefit from more frequent interaction with the FDA. Additionally, if the PFS end point is reached, the company will be eligible for an accelerated approval, priority review, and the ability to submit a rolling biologic license application.
In addition to the Fast Track Designation, VBL Therapeutics has also received an Orphan Drug Designation for ofra-vec as a potential treatment for ovarian cancer. This designation provides several incentives, according to the FDA, including tax credits for qualified clinical testing. Moreover, a company developing an orphan product is not required to pay prescription drug user fees when submitting a marketing application for the designated indication.