FDA Grants Rare Pediatric Drug Designation to VCN-01 for Retinoblastoma

The FDA has granted rare pediatric drug designation to VCN-01 for the treatment of patients with retinoblastoma, following its prior receipt of orphan drug designation from the regulatory agency in February 2022.^1,2

“The FDA’s decision to grant rare pediatric drug designation to VCN-01 highlights the urgent need for new treatment options for pediatric patients with retinoblastoma,” Steven A. Shallcross, chief executive officer of Theriva Biologics, said in a news release.1 “We are encouraged by this important step forward and, in parallel, continue to work closely with leading physicians and regulatory agencies to refine our clinical strategy for VCN-01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma.

“Most recently, results from the investigator-sponsored phase 1 trial evaluating the safety and activity of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma were determined to be positive by the study monitoring committee. Data from this study will further inform our clinical development pathway in this area of high unmet need,” Shallcross added.

VCN-01 is a systemic, selective, stroma-degrading oncolytic adenovirus designed to replicate within primary tumor and metastatic cells and degrade the tumor stroma. Because of its mechanism of action, VCN-01 can lyse tumor cells, enhance the reach of concurrent chemotherapy, and boost tumor immunogenicity.¹

In April 2024, Theriva announced positive topline results from its phase 1 trial (NCT03284268) in patients with intraocular retinoblastoma refractory to chemotherapy or radiotherapy. The phase 1, open-label, dose-escalation trial enrolled patients between 1 and 12 years of age whose only recommended treatment was enucleation. Patients needed to have retinoblastoma with a somatic RB1 mutation and an active tumor in a single eye; or a germinal RB1 mutation with active tumor(s) in an eye, and a contralateral eye that was unaffected, enucleated, or without tumor activity.^3,4

VCN-01 was administered in 2 intravitreal injections 14 days apart at doses of 2 x 10⁹ vp per eye (n = 1) or 2 x 10¹⁰ vp per eye (n = 8).³

Findings from the single-center trial demonstrated that VCN-01 was well tolerated in evaluable patients (n = 9). Most treatment-related adverse effects were grade 1 or 2. No dose-limiting toxicities were reported, and ocular or systemic toxicities were all grade 3 or lower. Investigators reported ocular inflammation and associated turbidity after VCN-01 injection. Inflammation was managed, and vitreous haze improved in some cases with the local and systemic administration of anti-inflammatory drugs.³

Regarding efficacy, 4 patients experienced a response, which was characterized by unequivocal improvement in vitreous seed density. Additionally, 3 patients have avoided eye enucleation as of data cutoff, including 1 patient who retained their eye after 4 years of follow-up.³

VCN-01 has also been investigated in several other solid tumors including pancreatic cancer, head and neck squamous cell carcinoma, ovarian cancer, and colorectal cancer,¹ earning fast track and orphan drug designation also in metastatic pancreatic cancer.^5,6

In a prior phase 1 study (NCT02045602) designed to evaluate the maximum-tolerated dose and recommended phase 2 dose (RP2D)/dose-limiting toxicity of the agent in patients with advanced refractory solid tumors, investigators identified 1 × 10¹³ vp/patient as the RP2D. Among the 6 patients with pancreatic cancer included in the third cohort who received the RP2D on day 1 followed by nab-paclitaxel (Abraxane) and gemcitabine on day 8, the overall response rate was 83%, with a median progression-free survival and overall survival of 6.3 months and 20.8 months, respectively.⁷

If the FDA approves a biologics license application for VCN-01 for patients with retinoblastoma, Theriva may be eligible to receive a priority review voucher that they can use to receive priority review for any subsequent marketing application or that can alternatively be sold or transferred.¹

References

1. 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 July 31, 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/
2. 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 July 31, 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
3. 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 July 31, 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/
4. Evaluate safety and the oncolitic adenovirus VCN-01 activity in patients with refractory retinoblastoma (RTB). ClinicalTrials.gov. Updated April 22, 2024. Accessed July 31, 2024. https://clinicaltrials.gov/study/NCT03284268
5. Theriva Biologics announces fast track designation granted by the U.S. FDA for VCN-01 for the treatment of metastatic pancreatic cancer. News release. Theriva Biologics. May 23, 2024. Accessed July 31, 2024. https://therivabio.com/press_releases/theriva-biologics-announces-fast-track-designation-granted-by-the-u-s-fda-for-vcn-01-for-the-treatment-of-metastatic-pancreatic-cancer/
6. Theriva Biologics announces orphan drug designation granted by the U.S. FDA for VCN-01 for the treatment of pancreatic cancer. News release. Theriva Biologics. June 27, 2023. Accessed July 31, 2024. https://therivabio.com/press_releases/theriva-biologics-announces-orphan-drug-designation-granted-by-the-u-s-fda-for-vcn-01-for-the-treatment-of-pancreatic-cancer/
7. Garcia-Carbonero R, Bazan-Peregrino M, Gil-Martin M, et al. Phase I, multicenter, open-label study of intravenous VCN-01 oncolytic adenovirus with or without nab-paclitaxel plus gemcitabine in patients with advanced solid tumors. J Immunother Cancer. 2022;10(3):e003255. doi:10.1136/jitc-2021-003255