FDA Grants Rare Pediatric Disease and Orphan Drug Designations to FL118 for Osteosarcoma Treatment
Key Insights
The FDA has granted both rare pediatric disease designation and orphan drug designation to FL118, a novel camptothecin derivative discovered at Roswell Park, for treating osteosarcoma (search) patients.
FL118 is a small molecule inhibitor derived from Xishu tree bark that has demonstrated broad anticancer activity in preclinical studies and targets the DDX5 (search) protein pathway.
These regulatory designations provide meaningful incentives for further development and may make the developer eligible for a priority review voucher if the drug receives approval.
The U.S. Food and Drug Administration has granted both rare pediatric disease designation and orphan drug designation to FL118 for the treatment of patients with osteosarcoma (search), according to announcements from Roswell Park Comprehensive Cancer Center. The dual designations strengthen the development position of this novel anticancer compound and may help support future clinical and strategic collaboration efforts.
FL118, chemically known as 10,11-methylenedioxy-20(S)-camptothecin (search), is a small molecule inhibitor that represents a novel approach to addressing therapeutic resistance in rare and aggressive malignancies. The compound is a camptothecin derivative based on a compound traditionally found in Xishu tree bark and used in traditional Chinese medicine.
Addressing Critical Unmet Medical Need
Osteosarcoma (search) is a rare, aggressive bone cancer that most commonly affects children, adolescents and young adults. Despite advances in surgery and chemotherapy, treatment options remain limited for patients with recurrent, metastatic or drug-resistant disease, highlighting the need for new therapeutic approaches.
"Receiving both Rare Pediatric Disease Designation and Orphan Drug Designation for FL118 in osteosarcoma (search) is an important milestone for this Roswell Park-discovered compound," stated Fengzhi Li, PhD, associate professor of oncology in the Department of Pharmacology and Therapeutics at Roswell Park and founder of Canget BioTekpharma (search). "These designations recognize the unmet medical needs in osteosarcoma and provide meaningful regulatory incentives that may help advance FL118 toward further development for pediatric and rare cancers."
Preclinical Evidence and Mechanism of Action
The regulatory decisions were supported by preclinical findings demonstrating that FL118 exhibits antitumor activity across multiple cancer models, with the potential to play a role in both cancer-survival and drug-resistance pathways. Preclinical research showed that FL118 degrades and binds to DDX5 (search), and according to data published in May 2022, FL118 was found to be a "bona fide" targeter of DDX5, which can act as a biomarker for predicting pancreatic ductal adenocarcinoma and colorectal cancer (search) tumor sensitivity to FL118.
"We consistently found that removal of DDX5 (search) from cancer cells resulted in slow tumor formation and growth, and tumors with high levels of DDX5 expression were more sensitive to FL118 treatment than tumors with low expression of this oncogenic protein," Li explained.
Xiang Ling, MD, PhD, a senior researcher on the FL118 team in the Department of Pharmacology & Therapeutics at Roswell Park, added: "Our research has confirmed that DDX5 (search) controls the expression of many other cancer-associated proteins, inducing survivin (search), Mcl-1, XIAP (search), c-Myc (search) and mutant KRAS (search), suggesting that DDX5 is a master regulator of cancer development and progression."
Broader Therapeutic Platform
FL118 has demonstrated unexpected anticancer activity with a favorable preclinical toxicity profile. Growing evidence suggests that FL118 may provide a novel drug platform for developing related compounds against additional rare or difficult-to-treat cancers such as malignant pleural mesothelioma (search).
"FL118 has demonstrated unexpected anticancer activity with a favorable preclinical toxicity profile, and our mechanistic studies continue to reveal important insights into how this compound works," said Ling.
Regulatory Pathway and Previous Designations
Under the provisions of the rare pediatric disease designation, if a new drug application for FL118 is accepted for the treatment of osteosarcoma (search), the developer may become eligible to receive a priority review voucher from the FDA. The FDA's Rare Pediatric Disease Designation program is designed to encourage development of treatments for serious or life-threatening diseases that primarily affect children.
FL118 previously received FDA orphan drug designation for the treatment of pancreatic cancer (search) in January 2024. In the reporting of that designation, investigators stated that FL118 had demonstrated the ability to eliminate pancreatic and colorectal tumor cells by binding to DDX5 (search).
FL118 was discovered by Li approximately 14 years ago as a compound derived from the same camptothecin-containing tree bark that was used in the development of irinotecan and topotecan. The compound is being developed by Canget BioTekpharma (search) LLC, a Roswell Park spinoff company.