After two rejections, on September 20, the U.S. FDA finally approved Fennec Pharmaceuticals' Pedmark (sodium thiosulfate) for the reduction of cisplatin-induced reduction in pediatric patients with locally non-metastatic solid tumors 1 month and older of hearing loss, became the first new drug in this field.

Pedmark is a water-soluble thiol compound used as a chemical reducing agent. Prolonged administration (4-8 hours) and high doses of Pedmark (16-20 g/m2) can protect 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. But deficiencies at the manufacturer's facility during the August 2020 pre-approval inspection led the FDA to issue a full response letter. A resubmission a year later also failed to change the FDA's mind. In April of this year, Fennec submitted its third application to go public.

Pedmark is indicated for pediatric patients aged 1 month to 18 years with locally non-metastatic solid tumors 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-term and permanent, and they currently require recourse to cochlear implants.

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

A total of 114 children with hepatoblastoma were enrolled in the SIOPEL 6 study to receive 6 cycles of cisplatin-based chemotherapy. The results showed that only 39% of patients in the cisplatin + Pedmark group developed grade 1 or higher hearing loss, compared with 68% in the cisplatin alone group, and the study met its primary endpoint.

Another COG ACCL0431 study included 125 pediatric patients with solid tumors who received chemotherapy. The results showed that the incidence of hearing loss in the Pedmark + cisplatin group and cisplatin alone group was 44% and 58%, respectively. Together, the two studies showed that Pedmark significantly reduced the risk of hearing impairment in patients with locally non-metastatic solid tumors.

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