Successfully treated childhood cancer often comes with a tradeoff: irreversible chemotherapy-induced hearing loss that can be managed only with lifelong hearing aids or a cochlear implant. Children undergoing cancer treatment now have drug alternative. The FDA has given the regulatory green light to a Fennec Pharmaceuticals drug that reduces the risk of hearing loss in patients receiving chemotherapy.
The regulatory nod announced Wednesday is a long-awaited decision that follows two rejections from the FDA. Approval of the Fennec drug, sodium thiosulfate, covers pediatric patients 1 month and older. Those patients must be receiving cisplatin-based chemotherapy for solid tumors that have not yet spread. Research Triangle Park, North Carolina-based Fennec will market its new therapy under the name Pedmark.
Cisplatin is a platinum-based chemotherapy. It’s an older therapy but a powerful one that is used to treat a wide range of cancers, including pediatric cancers. The platinum in these drugs damages the DNA of cancer cells, which prevents them from multiplying. The problem with cisplatin is that the drug’s toxic effects on cancer cells also sparks side effects elsewhere in the body. One of those side effects is permanent hearing loss stemming from the drug’s damaging effects on cochlear hair cells in the ear.
Sodium thiosulfate, the active pharmaceutical ingredient in Pedmark, is a compound whose initial use was treating metal poisoning. It later found additional medical applications treating cyanide poisoning and cisplatin toxicity. Pedmark is a proprietary formulation of sodium thiosulfate, developed from intellectual property licensed from Oregon Health & Science University. According to the Pedmark label, sodium thiosulfate directly interacts with cisplatin to produce an inactive form of platinum. In addition, the drug can enter cells sparking activity that may further reduce the risk of chemo-induced hearing loss.
The FDA based its approval on the results of two open-label clinical trials enrolling 239 total participants. Those patients were randomly assigned to receive either cisplatin and the Fennec drug dosed according to body weight, or cisplatin alone. Both clinical trials showed that the incidence of hearing loss was lower in the groups given the Fennec drug plus cisplatin compared to those treated with cisplatin alone. The drug’s efficacy was not the problem for Fennec. Manufacturing was.
Fennec initially completed its application for FDA approval in early 2020. In August of that year, the FDA sent the company a complete response letter that flagged problems with a third-party manufacturing facility for the drug. No safety or efficacy issues were raised, nor did the agency did ask for more clinical data. Fennec resubmitted its application in May 2021. The FDA rejected the drug last November, again citing manufacturing problems. In March, the biotech submitted an application for the third time. The FDA accepted it in April and set a Sept. 23 target date for a regulatory decision.
The Fennec drug is administered as a 15-minute intravenous infusion. It is given after cisplatin infusions that can last from one to six hours. The drug label states that Pedmark may not reduce the hearing loss risk following cisplatin infusions longer than six hours because hearing loss may have already occurred. The most common side effects reported in the clinical trials included vomiting, nausea, as well as abnormal blood levels of hemoglobin, sodium, and potassium.
In its second quarter 2022 financial report, Fennec said it had built out a commercial team in anticipation of Pedmark’s approval and planned drug launch. The company reported a cash position of $14.9 million as of June 30, a sum that reflects expenses made for Pedmark’s resubmission and pre-commercialization work for the drug. In Late August, the company secured $5 million under a debt financing agreement with Petrichor Healthcare Capital Management. According to the agreement, Fennec is set to receive another $20 million upon FDA approval of Pedmark by Sept. 30. The deal gives Fennec the flexibility to receive up to $20 million more in additional financing.
Pedmark is Fennec’s only product. The company did not answer emailed questions about Pedmark’s price or the planned launch date for the drug. Through a spokeswoman, the company said only that “Pedmark represents an important new tool for oncologists in their efforts to improve clinical outcomes for their pediatric patients. Fennec looks forward to working with the pediatric oncology community to bring Pedmark to patients in the near future.”