Regulatory Affairs

Fennec Pharmaceuticals' Pedmark gets FDA breakthrough status

PBR Staff Writer Published 28 March 2018

Fennec Pharmaceuticals has secured breakthrough therapy designation from the US Food and Drug Administration (FDA) for Pedmark to prevent cisplatin-related ototoxicity in pediatric patients with standard risk hepatoblastoma (SR-HB).

Pedmark, a formulation of sodium thiosulfate (STS), is a water-soluble thiol compound that serves as a chemical reducing agent.

Delayed administration (between four to eight hours) of high dose Pemark (16–20 g/m²) is said to provide protection against platinum-induced ototoxicity in animal models and patients.

STS was assessed by cooperative groups in two phase 3 clinical studies of survival and reduction of ototoxicity, including The Clinical Oncology Group Protocol ACCL0431 and SIOPEL 6. Both trials have been completed.

The COG ACCL0431 protocol recruited one of five childhood cancers generally treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumor, osteosarcoma, neuroblastoma, and medulloblastoma.

Fennec enrolled only hepatoblastoma patients with localized tumors in SIOPEL 6 protocol.

According to Fennec, Pedmark holds capacity to prevent chemotherapy-induced hearing loss and is the first available agent approved for this condition.

When Pedmark is administered about six hours after cisplatin, it deactivates he metabolic by-products of cisplatin circulating in the plasma, which are responsible for hearing loss.

The anticancer activity of cisplatin takes place during the first two hours after administration when the free (unbound) cisplatin distributes into the cancer cells. The cisplatin that stays in the plasma is either excreted or metabolically altered to reduce its anticancer activity.

Pedmark will inactivate the residual activity of metabolites in the plasma to neutralize their ability to cause hearing loss.

Fennec president and CEO Rosty Raykov said: "The decision by the FDA to grant PEDMARK the first Breakthrough Therapy designation for the prevention of cisplatin ototoxicity reflects a recognition of the promising efficacy and safety data generated from SIOPEL 6 and COG ACCL0431 studies.

“We believe the recent receipt of Fast Track designation, and today, Breakthrough Therapy designation highlights the current lack of safe and effective treatments and overwhelming need to address this serious condition.”

Image: The FDA campus in New Hampshire Ave, Silver Spring, Maryland. Photo: courtesy of The U.S. Food and Drug Administration.