VCN-01 Earns Orphan Medicinal Product Designation in Europe for Retinoblastoma

Steven A. Shallcross, CEO of Theriva Biologics

Following a recommendation from the European Medicines Agency, the European Commission (EC) has granted orphan medicinal product designation to the systemic, selective, stroma-degrading oncolytic adenovirus VCN-01 for the treatment of patients with retinoblastoma.¹

The oncovirus is intended to selectively and aggressively replicate in tumor cells and degrade the tumor stroma, which represents a physical and immunosuppressive barrier to cancer treatment. VCN-01 is designed to produce antitumor effects by selectively infecting and lysing tumor cells; increasing the access and perfusion of chemotherapy; and increasing tumor immunogenicity and exposing the tumor to the immune system and immunotherapy.

“We are very pleased with the EC’s grant of orphan medicinal product designation to VCN-01, emphasizing the urgent need for new treatment options for retinoblastoma,” Steven A. Shallcross, chief executive officer of Theriva Biologics, stated in a news release. “We have previously reported encouraging results from an investigator sponsored phase 1 trial [NCT03284268] evaluating the safety and activity of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma, and we are working closely with leading physicians and regulatory agencies worldwide to refine our clinical strategy for VCN-01 as an adjunct to chemotherapy in children with this challenging disease.”

The FDA previously granted orphan drug designation and rare pediatric drug designation to VCN-01 for the treatment of patients with retinoblastoma in February 2022 and July 2024, respectively.^2,3

Previously reported topline data from a phase 1 trial investigating VCN-01 in pediatric patients with intraocular retinoblastoma that was refractory to chemotherapy or radiotherapy showed that the 2 doses of treatment were well tolerated, and the majority of adverse effects (AEs) were grade 1 or 2.⁴ No dose-limiting toxicities were reported, and no ocular or systemic AEs of grade 3 or higher were reported in treated patients (n = 9).

No changes in retinal function were reported among treated patients; 4 patients achieved a response, defined as unequivocal improvement in vitreous seed density. Three patients avoided eye enucleation as of data cutoff, and 1 patient retained their eye after 4 years of follow-up.

The single-center, open-label, dose-escalation, phase 1 study enrolled patients 1 to 12 years of age with retinoblastoma harboring a somatic RB1 mutation with an active tumor in a single eye, or those harboring germinal RB1 mutations with active tumor(s) in an eye with the contralateral eye being unaffected, enucleated, or without tumor activity.⁵ Patients needed to be refractory to chemotherapy or radiotherapy. Other key inclusion criteria consisted of adequate renal, hepatic, and marrow function.

Patients were excluded if they had factors that would require immediate enucleation of the affected eye, including glaucoma, rubeosis iridis, or anterior chamber involvement; had uncontrolled epilepsy with anticonvulsant treatment or cardiac disease not compensated by treatment; active infections; had trilateral retinoblastoma; had extraocular spread; or received attenuated or live vaccines within 30 days of enrollment.

Enrolled patients received two intravitreal injections of VCN-01 14 days apart at a dose of 2 x 109 vp per eye (n = 1) or 2 x 1010 vp per eye (n = 8).⁴

The incidence of treatment-emergent AEs served as the trial’s primary end point.⁵ Secondary end points included tumor response; the presence of VCN-01 in blood samples, aqueous humor, ocular surface, and nasal swabs; and immune response.

Based on these phase 1 data, Theriva Biologics intends to launch a phase 2 study to further investigate VCN-01 in patients with retinoblastoma.⁴

References

1. Theriva Biologics announces orphan medicinal product designation granted by the European Commission to VCN-01 for the treatment of retinoblastoma. News release. Theriva Biologics. October 16, 2024. Accessed October 16, 2024. https://therivabio.com/press_releases/theriva-biologics-announces-orphan-medicinal-product-designation-granted-by-the-european-commission-to-vcn-01-for-the-treatment-of-retinoblastoma/
2. Theriva Biologics receives rare pediatric drug designation by the U.S. FDA for VCN-01 for the treatment of retinoblastoma. News release. Theriva Biologics. July 31, 2024. Accessed October 16, 2024. https://therivabio.com/press_releases/theriva-biologics-receives-rare-pediatric-drug-designation-by-the-u-s-fda-for-vcn-01-for-the-treatment-of-retinoblastoma/
3. Synthetic Biologics announces VCN Biosciences’ VCN-01 receives orphan drug designation for retinoblastoma from the U.S. FDA. News release. Synthetic Biologics, Inc. February 8, 2022. Accessed October 16, 2024. https://www.prnewswire.com/news-releases/synthetic-biologics-announces-vcn-biosciences-vcn-01-receives-orphan-drug-designation-for-retinoblastoma-from-the-us-fda-301477312.html
4. Theriva Biologics announces positive topline data from investigator sponsored phase 1 trial of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma. News release. Theriva Biologics. April 23, 2024. Accessed October 16, 2024. https://therivabio.com/press_releases/theriva-biologics-announces-positive-topline-data-from-investigator-sponsored-phase-1-trial-of-intravitreal-vcn-01-in-pediatric-patients-with-refractory-retinoblastoma/
5. Evaluate safety and the oncolitic adenovirus VCN-01 activity in patients with refractory retinoblastoma (RTB). ClinicalTrials.gov. Updated August 27, 2024. Accessed October 16, 2024. https://clinicaltrials.gov/study/NCT03284268