FDA Grants Priority Review to Naxitamab in R/R High-Risk Neuroblastoma

June 2, 2020
Nichole Tucker

Nichole Tucker, MA, is the Web Editor for Targeted Oncology. Tucker received her Bachelor of Arts in Mass Communications from Virginia State University and her Master of Arts in Media & International Conflict from University College Dublin.

"We believe that the FDA’s acceptance of our BLA for priority review of our first leading antibody compound, naxitamab, is a significant achievement for Y-mAbs and a crucial step forward as we anticipate that naxitamab if approved, can address a significant unmet medical need for [patients] with relapsed/refractory high-risk neuroblastoma."

The FDA has granted Priority Review to the recently accepted Biologics License Application (BLA) for naxitamab (Danyelza) as treatment of patients with relapsed/refractory high-risk neuroblastoma. Without an advisory board meeting, the Prescription Drug User Fee Act action date for naxitamab is set for November 30, 2020.1

“We believe that the FDA’s acceptance of our BLA for priority review of our first leading antibody compound, Danyelza (naxitamab), is a significant achievement for Y-mAbs and a crucial step forward as we anticipate that Danyelza if approved, can address a significant unmet medical need for children with relapsed/refractory high-risk neuroblastoma,” stated Thomas Gad, founder, chairman, president and head of Business Development and Strategy.

Data from a phase 2 study, 12-230 ,served as basis for the BLA. An update was announced in October of 2019 showing an overall response rate (ORR) of 78% in the subgroup of 28 patients with primary refractory high-risk neuroblastoma. This subgroup also had a 50% 2-year progression-free survival (PFS) rate. In seperate subgroup of 30 patients with relapsed neuroblastoma resistant to salvage therapy, the ORR was 37% and the PFS rate was 36%. Finally, in the subgroup of 44 patients with high-risk neuroblastoma who are in second or later complete remission, the PFS rate was 52%, but patients were not evaluable for ORR.2

Findings from naxitamab as treatment of relapsed/refractory high-risk neuroblastoma were also presented in a different study by Jaume Mora, MD, PhD, in a poster at the 2020 American Society of Clinical Oncology Virtual Scientific Program and showed potential for naxitamab for treatment in the outpatient setting.3

At a data cutoff of June 2019, data from 24 patients were available from the study. In the study population, the median age was 5.0 years (range, 1-10 years). Thirty-six percent of the children were female and 64% were male. In terms of race, 48% of patients were classified as white, 48% were Asian, and 4% were identified as other.

Baseline screening showed MYCN amplification in 16% (4 out of 25) and gain in 4% of patients (1 out of 25). However, 56% had no gain or amplification (14 out of 25), and 24% of patients had unknown MYCN amplification status (6 out of 25). The majority of patients (84%) were stage 4 (21 out of 25). There were no stage 2A, 2B, or 4S patients, and for 12% of patients, the INSS stage at diagnosis was not reported. A prognostic evaluation revealed that most patients (64%) had unfavorable histology (16 out of 25), and only 4% had favorable histology (1 out of 25). For 32% of participants, no prognostic group was reported ( 8 out of 25). For prior treatment, 23% of patients had prior surgery (23 out of 25), 96% had prior chemotherapy (24 out of 25), and 36% had prior radiation (9 out of 25).

Regarding neuroblastoma location and status at baseline, the disease was mainly located in both the bone and bone marrow (48%, 12 out of 25). The disease was located in the bone only in 44% of patients (11 out of 25), and in the bone marrow only in 8% of patients (2 out of 25). Sixty-four percent of patients were primary refractory (16 out of 25), and 36% had incomplete responses to salvage therapy (9 out 25).

At a median follow-up of 30 weeks (range, 6-48), the efficacy analysis showed an overall response rate (ORR) of 88% (95% CI, 62%-98%) in the primary refractory group, including a complete response (CR) rate of 81% (95% CI, 54%-96%). The group of 8 patients with incomplete response to salvage therapy had an ORR of 63% (85% CI, 24%-91%), with a CR rate of 50% (95% CI, 16%-84%). Overall, objective responses were seen in 19 patients in the study, showing an ORR of 79% (95% CI, 58%-93%) and a CR rate of 71% (95% CI, 49%-87%).

The median progression-free survival was 24 weeks with naxitamab (95% CI, 26-not estimable).

Grade 3 or 4 treatment-emergent adverse events (TEAEs) were reported in 10% of patients overall per the Common Terminology Criteria for Adverse Events, and overall 88% of patients experienced at least 1 grade 3/4 TEAE. Most events fell under the category of general disorder and administration site conditions (72%). The most common grade 3/4 TEAEs were pain (72%), vascular disorders (60%), and hypertension (60%). There were 6 serious TEAEs reported in 5 patients, which included 4 events of an anaphylactic reaction, 1 pyrexia events, and 1 respiratory depression event. Additionally, 8% of patients (2 out of 25) experienced anti-drug antibody formation.

The study of naxitamab, a humanized monoclonal antibody that targets GD2 expressed in neuroblastoma, was an international, multicenter clinical trial. Naxitamab was administered to patients in this study at 9mg.kg, which was divided into 3 doses given over 4 weeks, intravenously. Infusions lasted 30 minutes to 60 minutes in an outpatient setting.

Based on this study, Mora et al considered naxitamab a unique option for the treatment of relapsed/refractory high-risk neuroblastoma in the outpatient setting. The finding presented at ASCO 2020 warrant further development of the drug.

Y-mabs Therapeutics, Inc, developer of naxitamab, plans to work closely with the FDA to ensure a smooth commercial launch for the drug if it is approved.1


Y-mAbs announces U.S. FDA acceptance of Biologics License Application for Danyelza™ (naxitamab) for the treatment of neuroblastoma for Priority Review. New release. Y-mAbs Therapeutics, Inc. June 2, 2020. Accessed June 2, 2020. https://bit.ly/300qA2H

Y-mAbs Announces Naxitamab Update. New release. Y-mAbs Therapeutics, Inc. October 25, 2019. Accessed June 2, 2020. https://bit.ly/3dvqSm9

Mora J, Chan GC, Morgenstern DA, et al. Naxitamab, a new generation anti-GD2 monoclonal antibody (mAb) for treatment of relapsed/refractory high-risk neuroblastoma (HR-NB). J Clin Oncol. 38: 2020 (suppl; abstr 10543). doi: 10.1200/JCO.2020.38.15_suppl.10543