FDA Grants Orphan Drug Exclusivity to Pedmark for Prevention of Platinum-Induced Ototoxicity in Pediatric Solid Tumors

The FDA has granted orphan drug exclusivity to sodium thiosulfate (Pedmark) injection, which is indicated to reduce the risk of platinum-induced ototoxicity in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors, according to an announcement from Fennec Pharmaceuticals.¹

In September 2022, the FDA approved sodium thiosulfate to reduce the risk of ototoxicity associated with cisplatin in pediatric patients aged 1 month and older with localized, nonmetastatic solid tumors.²

The 7-year market exclusivity for sodium thiosulfate began on September 20, 2022, the date of its FDA approval, and continues until September 20, 2029.

“We are pleased that the FDA has granted orphan drug exclusivity to [sodium thiosulfate], which represents an important breakthrough treatment option for the pediatric cancer community,” Rosty Raykov, chief executive officer of Fennec Pharmaceuticals, stated in a news release. “Further, as the first and only FDA approved drug for the treatment of pediatric cancer patients with localized, non-metastatic solid tumors at risk for cisplatin-induced hearing loss, we will continue to focus on strengthening our patent portfolio to extend intellectual property protection for [sodium thiosulfate] beyond the 7 years provided with orphan drug exclusivity.”

The FDA approval was based on data from the phase 3 SIOPEL 6 (NCT00652132) and COG ACCL0431 (NCT00716976) trials, which both examined the cisplatin with or without sodium thiosulfate in pediatric patients.

Fennec Pharmaceuticals originally submitted a new drug application (NDA) for sodium thiosulfate and received a priority review designation from the FDA in April 2020.³ However, the FDA issued a complete response letter (CRL) to the company in August 2020 following a pre-approval inspection of the manufacturing facility for sodium thiosulfate revealed deficiencies that resulted in a Form 483, detailing conditions or practices that needed to be addressed before the agent could receive approval.⁴

Fennec resubmitted the NDA in May 2021.⁵ However, in November 2021, the FDA issued a second CRL to the company after identifying further manufacturing deficiencies.⁶ In April 2022, the FDA accepted the NDA resubmission for filing prior to the September 2022 approval.⁷

In the SIOPEL 6 trial, 39% of patients with standard-risk hepatoblastoma who received sodium thiosulfate with cisplatin experienced hearing loss, compared with 68% for patients given cisplatin alone (unadjusted relative risk, 0.58; 95% CI, 0.40-0.83).⁸

The trial randomly assigned patients 1:1 to receive cisplatin-based chemotherapy with (n = 61) or without (n = 53) sodium thiosulfate. The agent was administered intravenously over 15 minutes 6 hours following each cisplatin infusion.

In COG ACCL0431, incidence of hearing loss was lower in the sodium thiosulfate/cisplatin arm vs the cisplatin-alone arm, at 44% and 58%, respectively (unadjusted relative risk, 0.75; 95% CI, 0.48-1.18) among 125 patients between the ages of 1 and 18 years of age.

Patients in this trial were also randomly assigned 1:1 to receive cisplatin with or without sodium thiosulfate, and sodium thiosulfate was administered 6 hours after each infusion of cisplatin.

Regarding safety, the most common toxicities reported in the 2 trials included vomiting, nausea, decreased hemoglobin, hypernatremia, 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 January 31, 2023. http://bit.ly/3XOGoAC
2. FDA Approves sodium thiosulfate to reduce the risk of ototoxicity associated with cisplatin in pediatric patients with localized, nonmetastatic solid tumors. News release. FDA. September 20, 2022. Accessed January 31, 2023. https://bit.ly/3BXm47E
3. Fennec Pharmaceuticals announces FDA filing acceptance and priority review of new drug application for Pedmark. News release. Fennec Pharmaceuticals. April 13, 2020. Accessed January 31, 2023. http://bit.ly/3JpAjX4
4. Fennec Pharmaceuticals receives complete response letter from the FDA for its new drug application for Pedmark to prevent ototoxicity associated with cisplatin in pediatric patients with localized, non-metastatic, solid tumors. News release. Fennec Pharmaceuticals. August 11, 2020. Accessed January 31, 2023. https://bit.ly/30LptDZ
5. Fennec Pharmaceuticals resubmits new drug application to US Food and Drug Administration for Pedmark. News release. Fennec Pharmaceuticals, Inc. May 28, 2021. Accessed January 31, 2023. https://bit.ly/3pj91FO
6. Fennec Pharmaceuticals receives complete response letter from the FDA for its new drug application for Pedmark to prevent ototoxicity associated with cisplatin in pediatric patients with localized, non-metastatic, solid tumors. News release. Fennec Pharmaceuticals. November 30, 2021. Accessed January 31, 2023. https://bit.ly/3izYcwq
7. Fennec Pharmaceuticals announces FDA acceptance for filing of new drug application resubmission for Pedmark. News release. Fennec Pharmaceuticals. April 27, 2022. Accessed January 31, 2023. https://bit.ly/37TCwJM
8. Pedmark. Prescribing information. Fennec Pharmaceuticals, Inc; 2022. Accessed January 31, 2023. https://bit.ly/3R1zd3Z