FDA Raises Questions About BLA for Omburtamab in Pediatric Metastatic Neuroblastoma

The FDA has expressed concern about the efficacy of 131I-omburtamab prior to a meeting of the regulatory agency’s Oncologic Drugs Advisory Committee (ODAC) to examine data supporting the biologic license application (BLA) seeking the agent’s approval for the treatment of pediatric patients with central nervous system (CNS)/leptomeningeal metastases from neuroblastoma.¹

In April 2022, a BLA for omburtamab for pediatric metastatic neuroblastoma was resubmitted to the FDA, and it was supported by findings from the pivotal phase 2 101 (NCT03275402) and 03-133 (NCT00089245) trials.²

In a briefing document prepared prior to the ODAC meeting scheduled for October 28, 2022, the FDA review team outlined 3 potential issues with the BLA and study 03-133:

• The external control population is not fit-for-purpose as a comparator for the overall survival (OS) benefit of omburtamab due to substantive differences between the study and control populations.
• Additional analyses performed by the FDA to examine bias showed that differences in OS cannot be reliably attributed to omburtamab.
• The BLA does not include reliable data on response rates to provide supportive evidence for treatment with omburtamab.

The uncertainty regarding the OS benefit of omburtamab has prompted the FDA to request discussions regarding the assessment of efficacy in the BLA. These discussions will cover whether real-world data from the Central Childhood German Cancer Registry are appropriate for the comparison of OS with study 03-133, given the differences in study populations, and whether additional data are needed to assess the benefit of omburtamab.

Previously reported data from study 03-133 showed that among 107 patients with CNS/leptomeningeal metastases from neuroblastoma who received up to 2 doses of the radiolabeled drug, omburtamab elicited a median OS of 50.8 months, though the final median OS had not yet been reached.³

The BLA for omburtamab was originally submitted to the FDA in August 2020.⁴ However, in October 2020, following a preliminary review of data submitted for the agent, the FDA issued a Refusal to File letter.⁵

Y-mAbs Therapeutics, Inc., planned to resubmit the BLA in April 2021 following a Type B meeting with the FDA, where the agency requested additional information surrounding the granularity of data from identified historical control groups used in the first BLA.⁶

In July 2017, the FDA granted a breakthrough therapy designation to omburtamab based on data from study 03-133.⁷

References

1. FDA. October 28, 2022 meeting of the Oncologic Drugs Advisory Committee. October 26, 2022. Accessed October 27, 2022. https://bit.ly/3W7gurg
2. Y-mAbs announces submission of omburtamab biologics license application to FDA. News release. Y-mAbs Therapeutics, Inc. April 1, 2022. Accessed October 27, 2022. https://bit.ly/3wXDgrI
3. Y-mAbs announces positive omburtamab clinical data. News release. Y-mAbs Therapeutics, Inc. October 28, 2019. Accessed June 30, 2020. https://bit.ly/2YKpw1W
4. Y-mAbs announces completion of submission of omburtamab biologics license application to FDA. News release. Y-mAbs Therapeutics, Inc. August 6, 2020. Accessed October 27, 2022. https://bit.ly/3khYdEQ
5. Y-mAbs provides regulatory update on omburtamab for the treatment of patients with neuroblastoma. News release. Y-mAbs Therapeutic, Inc. October 5, 2020. Accessed October 27, 2022. https://bit.ly/30Dgq7B
6. Y-mAbs provides regulatory update on omburtamab. News release. Y-mAbs Therapeutics, Inc. April 20, 2021. Accessed October 27, 2022. https://bit.ly/3dyYhyD
7. Burtomab receives breakthrough therapy designation for advanced form of pediatric cancer. News release. Business Wire. June 7, 2017. Accessed October 27, 2022. https://bwnews.pr/2NJPf49