FDA Issues Complete Response Letter for Omburtamab BLA for Pediatric Metastatic Neuroblastoma

The FDA has issued a complete response letter (CRL) to the biologics license application (BLA) seeking the approval of 131I-omburtamab for the treatment of pediatric patients with central nervous system (CNS)/leptomeningeal metastases from neuroblastoma.¹

After completing a review of the BLA, the regulatory agency determined that it was unable to approve the BLA in its current form. The decision followed concerns expressed by the regulatory agency prior to an Oncologic Drugs Advisory Committee (ODAC) meeting in October 2022.² On October 28, 2022, in a 16 to 0 vote, ODAC voted that sufficient evidence was not provided to conclude omburtamab improves overall survival in this patient population.³

The CRL included a recommendation for Y-mAbs Therapeutics, Inc., the developer of omburtamab, to meet with the FDA to discuss adequate and well-controlled trial design to better demonstrate substantial evidence of the effectiveness of omburtamab and better assess its risk/benefit profile.

The company said it is assessing the implications of the CRL and what it means for the omburtamab program.

“We are disappointed by the CRL but not surprised based on the outcome of the ODAC meeting on October 28. We want to express our gratitude to all the patients, their families, and investigators who have participated in our clinical trials and advocated for the advancement of omburtamab,” Thomas Gad, president and interim chief executive officer of Y-mAbs Therapeutics, Inc., stated in a press release. “While we evaluate the implications of the CRL for the future of omburtamab, we are excited about refining our focus primarily to drive growth from Danyelza [naxitamab-gqgk] and validate our SADA platform in the clinic, with the goal of bringing innovative solutions to patients and value to our shareholders.”

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.⁴

Data from study 03-133 showed that among 107 patients with CNS/leptomeningeal metastases from neuroblastoma who received up to 2 doses of omburtamab, the median OS was 50.8 months, though the final median OS had not yet been reached.⁵ This was an improvement from the median OS of 47.1 months based on a prior data readout from the first 93 patients on the trial.

The BLA for omburtamab was originally submitted to the FDA in August 2020.⁶ However, in October 2020, following a preliminary review of data submitted for the agent, the FDA issued a Refusal to File letter.⁷

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.⁸

References

1. Y-mAbs announces complete response letter for omburtamab biologics license application. News release. Y-mAbs Therapeutics, Inc. December 1, 2022. Accessed December 2, 2022. https://bit.ly/3VJJZi3
2. FDA. October 28, 2022 meeting of the Oncologic Drugs Advisory Committee. October 26, 2022. Accessed December 2, 2022. https://bit.ly/3W7gurg
3. Y-mAbs announces outcome of FDA Advisory Committee Meeting on omburtamab. News release. Y-mAbs Therapeutics, Inc. October 28, 2022. Accessed December 2, 2022. https://bit.ly/3SRZ8fk
4. Y-mAbs announces submission of omburtamab biologics license application to FDA. News release. Y-mAbs Therapeutics, Inc. April 1, 2022. Accessed December 2, 2022. https://bit.ly/3wXDgrI
5. Y-mAbs announces positive omburtamab clinical data. News release. Y-mAbs Therapeutics, Inc. October 28, 2019. Accessed December 2, 2022. https://bit.ly/2YKpw1W
6. Y-mAbs announces completion of submission of omburtamab biologics license application to FDA. News release. Y-mAbs Therapeutics, Inc. August 6, 2020. Accessed December 2, 2022. https://bit.ly/3khYdEQ
7. Y-mAbs provides regulatory update on omburtamab for the treatment of patients with neuroblastoma. News release. Y-mAbs Therapeutic, Inc. October 5, 2020. Accessed December 2, 2022. https://bit.ly/30Dgq7B
8. Y-mAbs provides regulatory update on omburtamab. News release. Y-mAbs Therapeutics, Inc. April 20, 2021. Accessed December 2, 2022. https://bit.ly/3dyYhyD