Fennec's Pedmark (sodium Thiosulfate) Received Priority Review By The US FDA!

- May 15, 2020-

Fennec Pharmaceuticals Inc is a professional pharmaceutical company dedicated to the development of Pedmark (a unique formula of sodium thiosulfate) for pediatric patients to prevent ototoxicity caused by platinum-containing chemotherapy. Recently, the company announced that the US Food and Drug Administration (FDA) has accepted Pedmark's new drug application (NDA) and granted priority review, while specifying the prescription drug user fee method (PDUFA) target date is August 10, 2020.


Pedmark is a research drug, which is a water-soluble thiol compound, used as a chemical reducing agent, prolonged administration (4-8 hours) of high-dose Pedmark (16-20g / m2) can protect animal models and patients from Ototoxicity induced by platinum.


The NDA application approved Pedmark for patients with localized, non-metastatic solid tumors from 1 month to less than 18 years of age to prevent ototoxicity caused by cisplatin chemotherapy. If approved, Pedmark will be the first product to prevent cisplatin-induced hearing loss in children. Previously, the FDA has granted Pedmark orphan drug qualification, fast-track qualification, and breakthrough drug qualification. Currently, Pedmark is also under review by the European Medicines Agency (EMA).


Cisplatin and other platinum compounds are the basic chemotherapeutic drugs for many childhood malignancies. Unfortunately, platinum-based treatments can cause ototoxicity or hearing loss, which is permanent and irreversible, and is especially harmful to survivors of childhood cancer.


In the United States and Europe, it is estimated that more than 10,000 children receive platinum-based chemotherapy every year. Among them, 40% -90% of children will have severe, irreversible ototoxicity. The incidence of ototoxicity in these children depends on the dose and duration of chemotherapy, and many of them require lifelong hearing aids. There are currently no drugs that can prevent this hearing loss, and only expensive, technically difficult, and sub-optimal cochlear implants (inner ear) implants have proven to provide certain benefits. Among patients with ototoxicity at critical stages of development, infants and young children lack verbal language development and literacy skills, and older children and adolescents lack social and emotional development and educational achievements.


Pedmark has been evaluated by the collaboration group in two phase III clinical studies to prevent and reduce ototoxicity, including the COG ACCL0431 study and the SIOPEL 6 study. Both studies have been successfully completed. The COG ACCL0431 study included five types of childhood cancers that were usually treated with intensive cisplatin chemotherapy for localized and disseminated diseases, including newly diagnosed hepatoblastoma, germ cell tumor, osteosarcoma, neuroblastoma, and medulla Cell tumor. The SIOPEL 6 study included only patients with hepatoblastoma with localized tumors.


COG ACCL0431


Pedmark can protect cells from platinum toxicity in a variety of ways. These chemical protection mechanisms are not mutually exclusive. Pedmark can inactivate the platinum complex and make it covalently bind to thiol without cytotoxicity. Although platinum in the blood circulation disappeared in large amounts after 4 hours of platinum administration, Pedmark's protection against platinum-related hearing loss was still effective after 8 hours of platinum administration. This indicates that Pedmark can bind to the platinum / protein complex, thereby minimizing its toxicity, and a potential mechanism for platinum to cause hearing loss is due to the deposition of protein-bound platinum in the cochlea.


Other mechanisms by which Pedmark protects ototoxicity are through the removal of reactive oxygen species (ROS) and the increase of endogenous reducing agents (such as GSH). In the inner ear, the cochlea can concentrate Pedmark in perilymph or endolymph, and can locally enhance the chemical protection of Pedmark against ototoxicity. Therefore, cisplatin-mediated (via ROS) hair cell apoptosis is hindered by the reducing properties of sodium thiosulfate (STS).