On March 21, 2022 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that its novel MDM2-p53 inhibitor, alrizomadlin (APG-115), was granted a Rare Pediatric Disease (RPD) designation by the US Food and Drug Administration (FDA), for the treatment of neuroblastoma (Press release, Ascentage Pharma, MAR 21, 2022, View Source [SID1234610495]). To date, alrizomadlin has received a total of six Orphan Drug Designations (ODDs) and two RPDs by the FDA.

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The Food and Drug Administration Safety and Innovation Act (FDASIA), came into effect in 2012, established the rare pediatric disease priority review voucher (PRV) program to reward sponsors for the development of novel therapies for the treatment of rare pediatric diseases. FDASIA defines RPDs as rare diseases or conditions (diseases with a prevalence of less than 200,000 patients in the US) primarily affecting individuals aged from birth to 18 years, including age groups from neonates, infants, children, to adolescents. Being qualified for the PRV is one of the main benefits of the RPD designation, as sponsors who are rewarded with the PRV are eligible for priority review of future New Drug Applications or Biologics License Applications, and they may also choose to have the PRV transferred to another sponsor, at an estimated value around several hundred million US dollars.

Neuroblastoma is a type of embryonic tumor arising from the peripheral sympathetic nervous system. It is the most common extracranial solid tumor in children and the third most common pediatric cancer[1]. According to the American Cancer Society (ACS), there are about 700 to 800 new cases of neuroblastoma each year in the United States. This number has remained about the same for many years. Due to its aggressive nature and high risk of metastasis, neuroblastoma accounts for up to 15% of all deaths caused by pediatric cancers[2]. It is mostly diagnosed in infancy with 41% of patients diagnosed in the first three months after birth, and most patients are diagnosed by the age of 5 years with a median age of diagnosis around 18 months[3].

Neuroblastoma is a serious condition that can be life-threatening to pediatric patients. Patients diagnosed as low-risk usually have a good prognosis. However, those diagnosed with high-risk disease are difficult to cure, with a large proportion of these patients eventually experiencing disease recurrence. Despite intense multimodal treatments, patients with high-risk neuroblastoma have a poor prognosis with an Event-Free Survival (EFS) of less than 50%. Patients with relapsed or refractory neuroblastoma are extremely difficult to cure, and there is no standard treatment for these patients.

Being developed by Ascentage Pharma, alrizomadlin is an orally administered, selective, small-molecule inhibitor of the MDM2 protein. Alrizomadlin has strong binding affinity to MDM2 and is designed to activate tumor suppression activity of p53 by blocking the MDM2-p53 protein-protein interaction. In earlier studies, APG-115 as a single agent has shown antitumor activity in in vitro and in vivo models of neuroblastoma, demonstrating a mechanism of action that supports the clinical development of the drug candidate in patients with neuroblastoma.

Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma, said, "In addition to the benefits provided by the ODD, the RPD designation offers sponsors the additional incentive of priority review status for their future marketing applications, encourages the drug development for the treatment of rare pediatric diseases. Alrizomadlin is a key drug candidate in our apoptosis-targeted pipeline. It has already been granted six ODDs, one Fast Track Designation (FTD), and two RPDs by the US FDA, thus signifies this asset’s clinical potential. This RPD will qualify this program for a PRV, which should help us better communicate with the FDA to hopefully accelerate the clinical development of alrizomadlin. We will initiate the clinical study in neuroblastoma as soon as possible in order to develop a new treatment option for those pediatric patients in need."

References

American Cancer Society. Cancer Facts & Figures 2014. Atlanta, Ga: American Cancer
Ward E, DeSantis C, et al. Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin. Mar-Apr 2014;64(2):83-103.
Shohet J, Foster J. Neuroblastoma. BMJ. 2017 May 3;357:j1863.