Fennec Pharmaceuticals Completes Rolling Submission of NDA to U.S. FDA for Pedmark; Submits MAA to European Medicines Agency

Fennec Pharmaceuticals Completes Rolling Submission of NDA to U.S. FDA for Pedmark; Submits MAA to European Medicines Agency

Fennec Pharmaceuticals announced it has completed its rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Pedmark (a unique formulation of sodium thiosulfate) for intravenous use and submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for sodium thiosulfate (tradename to be determined). The Pedmark indication requested is for the prevention of ototoxicity induced by cisplatin chemotherapy in patients one month to < 18 years of age with localized, non-metastatic, solid tumors.

Fennec’s Pedmark regulatory submissions follow a pre-NDA meeting with the FDA in December 2018 after which Fennec initiated a rolling NDA; and pre-submission meetings with the EMA and an approved pediatric investigation plan (PIP). Both applications are based upon clinical results from two pivotal Phase 3 clinical trials:

  • SIOPEL 6 conducted by the International Childhood Liver Tumor Strategy Group (SIOPEL) with results published in the New England Journal of Medicine in June 2018
  • ACCL0431 conducted by the Children’s Oncology Group (COG) with results published in Lancet Oncology in 2016.

The FDA has a 60-day review period to determine whether the Pedmark NDA is acceptable for filing. If Pedmark is granted a priority review, the Prescription Drug User Fee Act (PDUFA) action date is expected in the third quarter of 2020.

Pedmark has been granted Orphan Drug, Breakthrough Therapy, and Fast Track designations from the FDA. 

About Pedmark (Sodium Thiosulfate (STS))

Pedmark may act in several ways to protect cells from platinum toxicity. Pedmark can inactivate platinum complexes and render them non-cytotoxic by covalently binding electrophilic platinum with thio. Although free platinum largely disappears from circulation four hours after administration in rats and pigs, protection against platinum-associated hearing loss by Pedmark was effective with delayed administration up to eight hours after platinum administration. This suggests that Pedmark avidly binds platinum/protein complexes thereby minimizing their toxicity and that a potential mechanism of the hearing loss caused by platinum results from the deposition of protein bound platinum in the cochlea. Other mechanisms by which Pedmark may protect against ototoxicity are by scavenging reactive oxygen species and by enhancing levels of endogenous reducing agents such as GSH. In the inner ear, the cochlea may concentrate Pedmark in the perilymph or endolymph and may locally enhance Pedmark chemoprotection against ototoxicity. Thus, it is suggested that cisplatin-mediated (via ROS) hair cell apoptosis is impeded by the reducing properties of STS. Source 

About ototoxicity induced by cisplatin chemotherapy

Cisplatin and other platinum compounds are essential chemotherapeutic agents for many pediatric malignancies. Unfortunately, platinum-based therapies cause ototoxicity, or hearing loss, which is permanent, irreversible and is particularly harmful to the survivors of pediatric cancer.

In the U.S. and Europe, it is estimated annually that over 10,000 children may receive platinum-based chemotherapy. The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids. There is currently no established preventive agent for this hearing loss and only expensive, technically difficult and sub-optimal cochlear (inner ear) implants have been shown to provide some benefit. Infants and young children that suffer ototoxicity at critical stages of development lack speech language development and literacy, and older children and adolescents lack social-emotional development and educational achievement.