Y-mAbs Therapeutics, an antibody-based oncology biotech, announced this week that the U.S. FDA had rejected the Biologics License Application for its neuroblastoma radioimmunotherapy, omburtamab.
While neuroblastoma is the most common extra cranial solid tumor diagnosed in children, it is still rare with roughly 650 cases reported in the U.S. every year. Treatment is usually a combination of surgery, radio, and chemotherapy, but there are no FDA-approved therapies specifically meant for this type of tumor.
Omburtamab is administered via intracerebroventricular injection (also called ICV injection) which is an invasive injection technique of substances directly into the cerebrospinal fluid in cerebral ventricles in order to bypass the blood-brain barrier. The radiolabeled monoclonal antibody binds to B7-H3 expressed on the tumor cells and the beta-emission from iodine 131 causes cell death.
The biotech was seeking traditional approval for the treatment of pediatric patients with neuroblastoma following standard central nervous disease treatment and included two studies to support its application, Study 03-133 and Study 101. Study 03-133 was its single-center, single-arm trial and Study 101, was its single-arm, multi-center confirmatory trial.
Preliminary data from 03-133 suggested an improvement in overall survival compared to a historical benchmark, but when the Oncologic Drugs Advisory Committee (ODAC) met to discuss the application back in Oct., the committee voted 16-0 against the drug's approval, citing major efficacy review issues.
In FDA briefing docs released prior to the AdComm meeting, one of the first issues addressed was that the external controls were not a relevant comparator due to clinically important differences between the populations, and therefore comparisons of survival were not reliable due to bias and sample size. In this case, the external control used was from the Central German Childhood Cancer Registry, which included 99% of pediatric cancer patients in Germany between 1990 and 2015. The FDA discussed population discrepancies such as differences in clinical care between the U.S. and Germany, the treatment era established, their baseline clinical status, and the fact that patients in the study received more intense treatment than the external control.
In its recent statement, Y-mAbs recognized that the FDA’s complete response letter rejection was consistent with the ODAC’s meetings and conclusions about the application. The biotech also said that the CRL includes a recommendation for meeting with the agency and discussing ways to establish a more adequate and well-controlled trial design to demonstrate evidence of effectiveness. As for the future of the drug, Y-mAbs said its “assessing the implications of the CRL and its plans for the omburtamab program.”
