FDA Rejects Pedmark NDA Again Citing Manufacturing Deficiencies

The application could not be approved in its present form due to manufacturing deficiencies.

The Food and Drug Administration (FDA) has issued a second Complete Response Letter (CRL) to Fennec Pharmaceuticals regarding the New Drug Application (NDA) for Pedmark™ (sodium thiosulfate) for the prevention of ototoxicity associated with cisplatin chemotherapy in patients 1 month to less than 18 years of age with localized, nonmetastatic solid tumors.

The NDA for Pedmark was resubmitted in May 2021, after the FDA issued a CRL in August 2020 citing deficiencies during a pre-approval inspection of the manufacturing facility. In the most recent CRL, the FDA again noted that the application could not be approved in its present form due to manufacturing deficiencies. The Company is requesting a Type A meeting to discuss the issues mentioned in the letter.

The application includes data from 2 pivotal phase 3 trials, SIOPEL 6 (ClinicalTrials.gov Identifier: NCT00652132) and ACCL0431 (ClinicalTrials.gov Identifier: NCT00716976), which compared the efficacy of sodium thiosulfate plus cisplatin to cisplatin alone for the prevention of cisplatin-induced hearing loss. Findings from both trials showed that the likelihood of hearing loss was significantly lower in the sodium thiosulfate treatment arm compared with cisplatin alone.

“We are steadfast in our commitment to reducing the risk of life-long hearing loss for children and young adults receiving cisplatin chemotherapy who currently have no approved therapies for this devastating condition,” said Rosty Raykov, CEO of Fennec Pharmaceuticals. “We will work closely with our current manufacturer as well as the FDA to fully address the issues raised in the letter.”

The FDA previously granted Breakthrough Therapy and Fast Track designations to Pedmark for this indication.


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 Inc. Accessed November 30, 2021. https://www.globenewswire.com/news-release/2021/11/30/2342800/0/en/Fennec-Pharmaceuticals-Receives-Complete-Response-Letter-from-the-FDA-for-its-New-Drug-Application-for-PEDMARK-to-Prevent-Ototoxicity-Associated-with-Cisplatin-in-Pediatric-Patient.html