FDA’s ODAC Unanimously Votes against Y-mAbs’ Pediatric Neuroblastoma Treatment

Al Drago/CQ Roll Call

Al Drago/CQ Roll Call

The FDA’s Oncologic Drugs Advisory Committee voted unanimously against approving l-omburtamab for children with a rare form of neuroblastoma, citing complex review issues.

Al Drago/CQ Roll Call/Getty Images

Y-mAbs Therapeutics took a regulatory blow Friday afternoon after the FDA’s Oncologic Drugs Advisory Committee voted unanimously against approving l-omburtamab for children with a rare form of neuroblastoma.

Specifically, the Committee voted that Y-mAbs had not provided sufficient evidence to conclude the therapy improves overall survival.

The 16-0 vote did not come as a surprise. In briefing documents released Wednesday, FDA scientists raised questions about the efficacy of l-omburtamab as a treatment for pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma.

ODAC cited “complex review issues” that led to a large degree of uncertainty over whether “the observed differences in overall survival between the single-arm Study 03-133 and external control populations are due to l-omburtamab” or other factors.

Ultimately, “the external control population is not fit-for-purpose as a comparator due to substantive differences between the study and control populations that limit the ability to attribute survival differences to the effect of I-omburtamab,” the Committee wrote.

Following the FDA’s own additional analyses to examine potential bias, “results reinforce that differences in survival cannot be reliably attributed to I-omburtamab,” the advisers wrote.

ODAC also cited a lack of reliable response rate data to provide supportive evidence of efficacy.

The FDA is not beholden to follow the recommendation of its advisory committees, but it usually does.

Company shares fell 35 percent in after-hours trading Friday.

Thomas Gad, president and interim CEO of Y-mAbs, expressed disappointment about the vote, citing the need for safe and effective treatments for patients with this type of neuroblastoma.

“Y-mAbs is committed to working closely with the FDA on their review of the Biologic License Application...for omburtamab ahead of their decision,” Gad said in a statement Friday afternoon.

CNS/LM is a rare and usually fatal complication of neuroblastoma in which the disease spreads to the membranes, or meninges, surrounding the brain and spinal cord in the central nervous system.

L-omburtamab targets an immune checkpoint molecule called B7-H3.

In May, the FDA accepted the BLA under priority review. It was supported by data from two Phase II studies, 101 and 03-133. The data from these clinical trials have not yet been published. The company anticipates publishing the data later this year.

This isn’t the first time Y-mAbs has faced difficulty getting omburtamab across the finish line. Two years ago, the FDA handed the company a Refusal to File letter. The letter raised concerns about Chemistry, Manufacturing and Control module and also said the Clinical module of the BLA required further detail.

Earlier this month, Y-mAbs announced interim results from 32 patients who participated in a separate study of omburtamab radiolabeled with Iodine-131. One-year overall survival was 73.5%, with a median follow-up of 25 months, the company reported.

Additionally, interim results from this study showed an objective response rate of 31.3% in patients with measurable disease. This was after central review based on criteria from both the Response Assessment in Neuro-Oncology and the European Association of Neuro-Oncology/European Society for Medical Oncology. A total of 75% of the patient population with measurable disease achieved disease control.

A little more than 40% of patients experienced a serious adverse event. Y-mAbs reported the SAEs were primarily related to myelosuppression.

The FDA has set a PDUFA date for Nov. 30.