MVdeltaC Receives FDA Orphan Drug Designation in Pleural Mesothelioma

Pleural Mesothelioma | Image by: Ashling Wahner &

MJH Life Sciences Using AI

The FDA has granted orphan drug designation to the oncolytic virus candidate MVdeltaC for the treatment of patients with pleural mesothelioma.1

This novel immunotherapy leverages a genetically modified attenuated Schwarz strain measles virus, specifically engineered to selectively replicate within tumor cells and induce immunogenic cell death, thereby reactivating “cold” tumors. Its dual mechanisms of direct oncolysis and immune activation are intended to improve clinical outcomes in patients with advanced solid tumors like pleural mesothelioma, which is considered a rare, aggressive cancer associated with high unmet need and a limited therapeutic arsenal.1,2

Notably, MVdeltaC demonstrates cancer cell–specific tropism through its use of CD46, a receptor that is overexpressed on the surface of many tumor types.2 Its antitumor activity was evaluated in vitro across human tumor cell lines, including mesothelioma, lung adenocarcinoma, hepatocarcinoma, and bladder, ovarian, and cervical cancers. In vivo efficacy was also assessed and confirmed following local administration in mesothelioma patient-derived xenograft models and in a syngeneic neuroblastoma model using immunocompetent A/J mice.

“With this designation, Oncovita is now well-positioned to enter the [United States] market with its modified attenuated measles virus for the treatment of [patients with] pleural mesothelioma,” Stéphane Champiat, MD, PhD, head of Medical Affairs at Oncovita, stated in a news release.1 “This recognition highlights the promise of this novel approach against one of the most aggressive cancers in medicine.”

Preclinical Data and Next Steps

In October 2023, Oncovita presented preclinical data for the MVdeltaC vaccine at the International Society for Vaccines Annual Congress.2 Results showed that the oncolytic vaccine exhibited 2- to 3-fold greater potency than standard measles virus in lysing human tumor cell lines and demonstrated robust oncolytic activity in both in vitro and in vivo models.

Over 70% of 127 human tumor cell lines spanning 8 cancer types displayed sensitivity to treatment with MVdeltaC. In vivo studies of NOD/SCID mice with human mesothelioma grafts showed that a single low-dose intraperitoneal injection of MVdeltaC led to a 60% to 70% reduction in tumor mass after 2 weeks. This antitumor activity was further confirmed in patient-derived xenograft models of mesothelioma and bladder cancer.

In immunocompetent A/J mice, 3 intratumoral injections of MVdeltaC generated complete responses per RECIST 1.1 criteria and a 72% survival rate, which increased to 100% when co-administered with an anti–CTLA-4 antibody. Moreover, ex vivo studies demonstrated that MVdeltaC infection triggered the release of danger signals and tumor-associated antigens. It also induced strong adaptive immune responses, including the activation of myeloid dendritic cells and plasmacytoid dendritic cells, and resulted in the cross-presentation of tumor-associated antigens to autologous T-cell lymphocytes.

Based on these preclinical findings, a first-in-human clinical trial is being planned for patients with solid tumors, with a specific focus on patients with checkpoint inhibitor–resistant disease.

“Receiving orphan drug designation from the FDA for MVdeltaC marks a major milestone for Oncovita and validates our approach of harnessing the potential of measles vaccine viruses to treat solid tumors, particularly rare and devastating cancers such as pleural mesothelioma,” Stéphane Altaba, chief executive officer of Oncovita, added in the news release.1 “This regulatory support strengthens our strategy to advance innovative immunotherapies as we prepare to enter clinical development with MVdeltaC by 2026.”

References

1. Oncovita receives FDA orphan drug designation for its lead oncolytic virus candidate MVdeltaC in the treatment of pleural mesothelioma. News release. Oncovita. June 4, 2025. Accessed June 12, 2025. https://www.oncovita.fr/news/oncovita-receives-fda-orphan-drug-designation-for-its-lead-oncolytic-virus-candidate-mvdeltac-in-the-treatment-of-pleural-mesothelioma/
2. MVdeltaC: a new therapeutic vaccine derived from measles vaccine with promising preclinical immuno-oncolytic activities (Abstract). News release. Oncovita. October 16, 2023. Accessed June 12, 2025. https://www.oncovita.fr/news/oncovita-presents-preclinical-data-on-its-promising-mvdeltac-oncolytic-vaccine-at-sitc-annual-meeting-2022/