Osteosarcoma Drug Earns Rare Pediatric Disease, Orphan Drug Designations

The FDA has granted rare pediatric disease designation and orphan drug designation to FL118 for the treatment of patients with osteosarcoma, according to a press release from Roswell Park.¹ FL118, otherwise known by its chemical name 10,11-methylenedioxy-20(S)-camptothecin, is a small molecule inhibitor that represents a novel approach to addressing therapeutic resistance in rare and aggressive malignancies. Specifically, it is a camptothecin derivative based on a compound traditionally found in Xishu tree bark.

Reportedly, 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. Furthermore, preclinical assessments have indicated that the agent provides a platform for treating other difficult-to-manage rare tumors, such as malignant pleural mesothelioma.

“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 Xiang Ling, MD, PhD, a senior researcher on the FL118 team in the Department of Pharmacology & Therapeutics at Roswell Park, in the press release.¹

Under the provisions of the rare pediatric disease designation, if a new drug application for FL118 is accepted for the treatment of osteosarcoma, the developer may become eligible to receive a priority review voucher from the FDA.

“Receiving both rare pediatric disease designation and orphan drug designation for FL118 in osteosarcoma 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, in the press release.¹ “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.”

Additional Information

In addition to these designations in osteosarcoma, FL118 previously was granted orphan drug designation for the treatment of pancreatic cancer in January 2024.² 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.

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. As previously noted, preclinical research showed that FL118 degrades and binds to DDX5. 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 tumor sensitivity to FL118.⁴

“We consistently found that removal of DDX5 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 said in that release.³

“Our research has confirmed that DDX5 controls the expression of many other cancer-associated proteins, inducing survivin, Mcl-1, XIAP, c-Myc and mutant KRAS, suggesting that DDX5 is a master regulator of cancer development and progression,” added Ling.³

References

1. FL118 granted FDA rare pediatric disease designation and orphan drug designation for osteosarcoma. News release. Roswell Park Comprehensive Cancer Center. May 19, 2026. Accessed May 21, 2026. https://tinyurl.com/4r6s7pzn
2. FL118, drug candidate discovered at Roswell Park, granted FDA orphan drug status for pancreatic cancer. News release. Roswell Park Comprehensive Cancer Center. January 24, 2024. Accessed May 21, 2026. https://tinyurl.com/5yhh3rwj
3. Roswell Park researchers identify molecular ‘glue’ that sticks to and degrades a cancer-causing protein. News release. Roswell Park Comprehensive Cancer Center. May 23, 2022. Accessed May 21, 2026. https://tinyurl.com/5yvua6cj
4. Ling X, Wu W, Aljahdali IAM, et al. FL118, acting as a 'molecular glue degrader', binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy. Clin Transl Med. 2022;12(5):e881. doi:10.1002/ctm2.881