FDA hands Y-mAbs refusal to file letter in one of its pediatric neuroblastoma programs
In what had looked like a promising year for Y-mAbs Therapeutics $YMAB as its two main neuroblastoma programs headed to the FDA, the company hit a roadblock Monday afternoon.
US regulators handed the company an RTF for omburtamab — the second of those two candidates — citing the need for more information on the manufacturing and clinical modules, Y-mAbs said. Although the company didn’t specify what the agency requested, Y-mAbs noted that it will be providing supplementary data from a Phase II study regarding tumor response from the first 24 patients in the trial.
Investors turned their noses up at the news, with Y-mAbs’ stock price plunging more than 18% in after-hours trading.
Y-mAbs had started submitting its BLA for omburtamab at the end of June, completing the rolling review application in August. With the RTF, Y-mAbs now expects to meet with the FDA and resubmit its omburtamab application before the end of 2020.
Its other neuroblastoma program, naxitamab, was accepted for priority review in early June with the FDA setting a PDUFA date for Nov 30.
Omburtamab is a monoclonal antibody that targets B7-H3, an immune checkpoint molecule that is widely expressed in tumor cells of several cancer types. Y-mAbs’ BLA is geared toward the treatment of pediatric patients with CNS/leptomeningeal metastases from neuroblastoma. Initially, the submission was based on the safety and efficacy results of two Phase II studies.
Naxitamab, meanwhile, targets GD2 — a common antigen on the cell surface of many different tumors, including neuroblastoma, melanoma, small cell lung cancer and brain tumors, as well as several sarcomas. The candidate was initially placed in a partial clinical hold for about 8 months between 2017 and 2018, but given that the FDA did not request an adcomm for the application, everything appears to be trending in the right direction. The candidate is aiming to treat r/r high-risk neuroblastoma in children.
Pediatric cancer is a personal focus for Y-mAbs founder Thomas Gad, whose daughter was diagnosed with high-risk neuroblastoma at age 2, according to the company’s S-1. She was treated with the mouse version of naxitamab at the time, but later relapsed and began taking omburtamab about 11 years ago. Since then, she has been disease-free.
With the old Genmab crew steering the ship, Y-mAbs has several other ongoing trials for omburtamab in other indications, such as front-line high-risk neuroblastoma and relapsed second-line osteosarcoma. The company is also studying naxitamab for the use in diffuse intrinsic pontine glioma and desmoplastic small round cell tumor.
Further down the pipeline, Y-mAbs is looking at a potential GD2-GD3 vaccine and a GD2-CD3 bispecific antibody.