FDA Receives BLA Resubmission for I-Omburtamab for CNS/Leptomeningeal Metastasis from Neuroblastoma

A biologics license application (BLA) has been re-submitted to the FDA seeking approval for I-omburtamab for the treatment of pediatric patients with central nervous system (CNS)/leptomeningeal metastasis from neuroblastoma, according to a press release by Y mAbs Therapeutics, Inc.¹

This resubmission follows a refusal to file letter from the FDA, stating that certain parts of the chemistry, manufacturing, and control module and the clinical module of the application were lacking important details.²

“I am excited to see the completion of Y-mAbs’ second BLA submission in neuroblastoma. As children treated for high-risk systemic neuroblastoma potentially experience longer systemic remissions, we expect more patients eventually relapsing with brain metastasis and there is currently no effective therapy beyond surgery and radiotherapy available for these patients.” stated Thomas Gad, founder, chairman and president, Y-mAbs, in a press release.

The new BLA is supported with findings from the pivotal studies 101 and 03-133. In the study 03-133, omburtamab monotherapy evaluated in patients with CNS/leptomeningeal metastatic from neuroblastoma, and in study 101, investigators assessed the combination of naxitamab (Danyelza) and omburtamab in patients with neuroblastoma.^3,4

Patients in the phase 1 study 03-133 were administered up to 2 doses of the agent. The goal of the study was to determine safety by the number of patients with treatment-related toxicities. In 107 evaluable patients, the median survival with omburtamab was 50.8 months with the final median not reached. The findings reported in 2019 were comparable with a prior reported of a 47.1-month survival in a group of 93 patients.³

In 68 patients with other CNS cancers–including medulloblastoma (n = 27), ependymoma (n = 9), and embryonal tumors with multilayered rosettes (n = 4), sarcoma (n = 9), melanoma (n = 5), and other tumors (n = 14)–201 injections of omburtamab were safely administered in the outpatient setting. Investigators identified no dose-limiting toxicities. Grade 1/2 fever, headache, and vomiting were rare adverse events (AEs) observed in these patients. Further, grade 3 chemical meningitis, and increasing communicating hydrocephalus were AEs requiring discontinuation of the agent.

In the pivotal 101 study, 17 patients were administered the combination of naxitamab and omburtamab, and followed for a median of 26 weeks. The overall survival (OS) rate observed with the combination was 87%, compared with 30% in a historic control.⁴

“We believe omburtamab can potentially address a significant unmet medical need for children with CNS/leptomeningeal metastasis from neuroblastoma, and we look forward to working with the FDA to bring omburtamab to the appropriate patients,” said Claus Moller, MD, PhD, chief executive officer, Y-mAbs, in a press release.

_REFERENCES:

_{1. Y-mAbs announces submission of omburtamab biologics license application to FDA. News release. Y-mAbs. March 31, 2022. Accessed April 1, 2022. https://bit.ly/3LC340j}

_{2. Y-mAbs provides regulatory update on omburtamab for the treatment of patients with neuroblastoma. News release. Y-mAbs. October, 2020. Accessed April 1, 2022.}

_{3. Y-mAbs announces positive omburtamab clinical data. News release. YmAbs. October 28, 2019. Accessed April 1, 2022. https://bit.ly/3NF1b4S}

_{4. Y-mAbs announces update on naxitamab and omburtamab in neuroblastoma. News release. October 16, 202. Accessed April 1, 2022. https://bit.ly/3uJwfbi}