FDA Grants Orphan Drug Exclusivity to Sodium Thiosulfate Injection for Pediatric Cancer

Sodium thiosulfate injection (Pedmark) has received FDA orphan drug exclusivity for reducing the risk of ototoxicity or hearing loss related to cisplatin use among pediatric patients 1 month or older with localized, non-metastatic tumors, according to a press release from Fennec Pharmaceuticals.¹

The FDA orphan drug exclusivity for sodium thiosulfate injections for pediatric patients with localized, non-metastatic tumors follows the FDA's approval of the injection in September 2022.

“We are pleased that the FDA has granted orphan drug exclusivity to [sodium thiosulfate injection], which represents an important breakthrough treatment option for the pediatric cancer community,” Rosty Raykov, chief executive officer of Fennec Pharmaceuticals, said in the press release.

The sodium thiosulfate injection was designed as a single-dose, ready-to-use treatment for intravenous use in pediatric patients. The agent demonstrated efficacy with an established dosing regimen across 2 open-label, randomized phase 3 studies.

The FDA previously approved the sodium thiosulfate injection for pediatric patients in September 2022.² The approval was supported by efficacy findings from the phase 3 SIOPEL6 trial (NCT00652132), which included a pediatric population with stage I to III liver cancer. The indication was also based on data from the phase 3 COG ACCL0431 trial (NCT00716976) in which the injection was assessed in newly diagnosed pediatric patients with germ cell tumors, hepatoblastoma, medulloblastoma, and neuroblastoma.

In the SIOPEL6 trial, sodium thiosulfate yielded a 39% hearing loss rate compared with 68% for patients who received cisplatin alone (HR, 0.58; 95% CI, 0.40-0.83). In the COG ACCL0431 trial, 44% of patients receiving the injection had hearing loss compared with 58% of those receiving cisplatin alone (HR, 0.75; 95% CI, 0.48-1.18).

Patients in the SIOPEL6 trial were randomly assigned 1:1 to either receive cisplatin-based chemotherapy plus or minus the sodium thiosulfate injection at several potential dose levels including 10 g/m², 15 g/m², and 20 g/m². Investigators of the COG ACCL0431 trial administered cisplatin at 200 mg/m² or more to patients with solid malignancies.

The primary end point of the SIOPEL6 and COG ACCL0431 trials was the incidence of hearing loss among pediatric patients. Secondary end points in both trials included overall survival and event-free survival.

For COG ACCL0431, patients 16 years and younger with a Karnofsky performance status of 50% to 100% were eligible to enroll along with those who were 16 years and younger with a Lansky performance status of 50% to 100% for those 16 or younger. Additional inclusion criteria included having an absolute granulocyte count of more than 1000/mm3 and not receiving prior chemotherapy with cisplatin or carboplatin.

To be included in the SIOPEL6 study, patients needed to be 18 years or younger but older than 1 month with histologically confirmed, standard risk, newly diagnosed hepatoblastoma. Those with recurrent disease, abnormal renal function, and who received prior chemotherapy were not able to enroll on the study.

Common adverse effects observed in the trials included vomiting, nausea, hypernatremia, hemoglobin decrease, and hypokalemia.

References

1. Fennec Pharmaceuticals announces Pedmark^® (sodium thiosulfate injection) receives orphan drug exclusivity from U.S FDA. News release. Fennec Pharmaceuticals. January 31, 2023. Accessed February 1, 2023. bit.ly/3HPPnw4
2. FDA approves sodium thiosulfate to reduce the risk of ototoxicity associated with cisplatin in pediatric patients with localized, non-metastatic solid tumors. News release. FDA. September 20, 2022. Accessed February 1, 2023. https://bit.ly/3DLjVgC