Sodium thiosulfate has been approved by the FDA to reduce hearing loss in children caused by chemotherapy

After being rejected twice, the FDA finally approved Fennec Pharmaceuticals' Pedmark (sodium thiosulfate) on the market on September 20 to reduce hearing loss caused by cisplatin in children with locally non-metastatic solid tumors for one month or more, becoming the first new drug in this field.

Pedmark is a water-soluble thiol compound used as a chemical reducing agent. Prolonged administration (4-8 h) and high doses of Pedmark(16-20g/m2) protected animal models and patients from platinum-induced ototoxicity.

The FDA previously granted Pedmark Orphan Drug Designation, Fast Track Designation and Breakthrough Drug Designation in 2018. However, deficiencies at the manufacturer's facility during a pre-approval inspection in August 2020 resulted in a full response letter from the FDA. A resubmission a year later failed to change the FDA's mind. In April, Fennec filed for its third listing.

Pedmark is indicated for pediatric patients aged 1 month to 18 years with locally metastatic solid tumors who have been treated with cisplatin infusion for no more than 6 hours. For this group of patients, the hearing loss caused by such chemotherapy is often long-lasting and permanent, and they now need cochlear implants.

The approval is based on two multicenter, open-label, randomized, controlled Phase III trials evaluating the efficacy and safety of cisplatin in pediatric patients receiving cisplatin.

The SIOPEL 6 study enrolled 114 pediatric patients with retinoblastoma who received six cycles of cisplatin-based chemotherapy. Results showed that only 39 percent of patients in the cisplatin plus Pedmark group had grade 1 or higher hearing loss, compared to 68 percent of patients in the cisplatin alone group, meeting the primary endpoint.

Another COG ACCL0431 study enrolled 125 pediatric patients with solid tumors undergoing chemotherapy. Results showed a 44 percent rate of hearing loss in the Pedmark+Cisplatin group and a 58 percent rate in Cisplatin alone.. Together, these two studies show that Pedmark significantly reduces the risk of hearing loss in patients with locally metastatic solid tumors.

Overall, the drug was safe and well tolerated, with the most common adverse effects (≥25%) in both studies being vomiting, nausea, decreased hemoglobin, hyponatremia, and hypokalemia