FDA Grants Rare Pediatric Disease Designation to Opaganib for Neuroblastoma

The US FDA has granted rare pediatric disease designation (RPDD) to opaganib (ABC294640) for the treatment of neuroblastoma.¹ The designation is in addition to an orphan drug designation (ODD) for the same indication that was previously granted by the FDA.

Together, these designations provide a suite of potential regulatory and financial incentives should the drug ultimately receive approval, including eligibility for a priority review voucher (PRV), 7 years of marketing exclusivity, accelerated development and review timelines, waiver of FDA Prescription Drug User Fee Act (PDUFA) application fees, and tax credits.

Opaganib is a first-in-class, orally administered, selective sphingosine kinase-2 (SPHK2) inhibitor currently under investigation across multiple oncologic, inflammatory, metabolic, and antiviral indications. The drug functions through inhibition of 3 sphingolipid-metabolizing enzymes: SPHK2, dihydroceramide desaturase 1 (DES1), and glucosylceramide synthase (GCS). This leads to induction of autophagy and apoptosis and disruption of intracellular signaling pathways relevant to tumor growth and viral replication.^1,2

Neuroblastoma Disease Context

Neuroblastoma is a malignancy arising from immature sympathoadrenal neuroblasts and most commonly affects infants and young children. It is the most frequently diagnosed cancer in infancy and accounts for approximately 10% of all pediatric malignancies and 15% of pediatric cancer-related deaths in the United States.^3,4 Approximately 750 children in the US are diagnosed annually, and an estimated 5500 cases are diagnosed globally each year among children aged 0 to 14.⁵

The disease typically originates in the adrenal medulla but may arise from sympathetic ganglia in the thorax, abdomen, or pelvis. While low- and intermediate-risk disease is associated with favorable outcomes, approximately 50% of patients present with high-risk neuroblastoma (HRNB), which carries a 5-year overall survival rate of roughly 50%.⁶ MYCN gene amplification, present in 40 to 50% of HRNB cases, is an established driver of aggressive disease and an oncogenic target of therapeutic interest. Current standard-of-care regimens for HRNB include induction chemotherapy, consolidation with high-dose chemotherapy and autologous stem cell rescue, radiation, and immunotherapy with dinutuximab (Unituxin). Despite improvements in recent decades, this multimodal approach leaves substantial room for further efficacy gains in the relapsed and refractory setting.

Proposed Mechanism in Neuroblastoma

The rationale for developing opaganib in neuroblastoma centers on its effect on sphingolipid metabolism and its downstream influence on the MYCN oncoprotein. Preclinical work published in Cancers in 2024 demonstrated that opaganib downregulates N-Myc (the protein product of MYCN) and suppresses neuroblastoma cell proliferation in vitro and in vivo, with activity observed regardless of MYCN amplification status.²

More recent data, presented at the 2026 American Association for Cancer Research (AACR) Annual Meeting, evaluated opaganib as a potential add-on to chemotherapy in models of relapsed/refractory HRNB. The abstract, authored by Hengst et al, examined opaganib in combination with oxaliplatin and doxorubicin as a salvage regimen. The investigators observed that opaganib appeared to directly destabilize N-Myc through increased ceramide production, enhancing apoptosis in combination with the cytotoxic agents tested.⁷ Investigators are engaged in discussions with Penn State University and the Beat Childhood Cancer consortium regarding further clinical development.¹

REFERENCES

1. RedHill's Opaganib Receives FDA Rare Pediatric Disease Designation for Neuroblastoma in Addition to Current Orphan Drug Designation. News release. RedHill Biopharma. June 9, 2026. Accessed June 11, 2026. https://tinyurl.com/24ymjj5f

2. Maines LW, Keller SN, Smith RA, Schrecengost RS, Smith CD. Opaganib Downregulates N-Myc Expression and Suppresses In Vitro and In Vivo Growth of Neuroblastoma Cells. Cancers (Basel). 2024 May 5;16(9):1779. doi: 10.3390/cancers16091779. PMID: 38730731; PMCID: PMC11082966.

3. Guild A, Mahapatra S, Allison J, et al. Neuroblastoma. [Updated 2026 May 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448111/

4. Yan P, Qi F, Bian L, Xu Y, Zhou J, Hu J, Ren L, Li M, Tang W. Comparison of Incidence and Outcomes of Neuroblastoma in Children, Adolescents, and Adults in the United States: A Surveillance, Epidemiology, and End Results (SEER) Program Population Study. Med Sci Monit. 2020 Nov 29;26:e927218. doi: 10.12659/MSM.927218. PMID: 33249420; PMCID: PMC7711874.

5. St. Jude Children’s Research Hospital. Neuroblastoma. Accessed June 11, 2026. https://tinyurl.com/4266yfuy

6. Flaadt T, Rehm J, Simon T, Hero B, Ladenstein RL, Lode HN, Grabow D, Nolte S, Crazzolara R, Greil J, Ebinger M, Abele M, Holzer U, Döring M, Schulte JH, Bader P, Schlegel PG, Eyrich M, Lang P, Klingebiel T, Handgretinger R. Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study. Cancers (Basel). 2025 Jan 5;17(1):149. doi: 10.3390/cancers17010149. PMID: 39796776; PMCID: PMC11720496.

7. Hengst J, Haque M, Younis M, et al. Abstract 7879: Opaganib in combination with oxaliplatin and doxorubicin as a novel salvage therapy for relapsed/refractory high-risk neuroblastoma. Cancer Res. 2026;86(7_Supplement):7879. doi:10.1158/1538-7445.AM2026-7879