RESEARCH TRIANGLE PARK, N.C. — Fennec Pharmaceuticals Inc. (NASDAQ: FENC; TSX: FRX), a specialty pharmaceutical company, today announced positive topline results from the investigator-initiated Phase 2/3 STS-J01 clinical trial evaluating PEDMARK® (sodium thiosulfate injection) for reducing cisplatin-induced ototoxicity in pediatric and adolescent and young adult (AYA) patients with non-metastatic solid tumors in Japan.
PEDMARK® is the first and only U.S. Food and Drug Administration (FDA)-approved therapy to reduce the risk of ototoxicity associated with cisplatin treatment in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors.
Assessing PEDMARK® in Pediatric Cisplatin Therapy
The study enrolled 27 patients in the primary cohort (ages 3–18 years) and 6 patients in exploratory cohorts. PEDMARK® was administered six hours after cisplatin infusion. The primary endpoint was met: 24% and 16% of evaluable patients experienced hearing loss as measured by American Speech-Language-Hearing Association (ASHA) criteria and Brock grading, respectively.
These findings compare favorably with PEDMARK®’s pivotal Phase 3 cisplatin-only studies, where 56% of children met ASHA criteria for clinically significant hearing loss (ACCL0431), and 63% met Brock Grade ≥1 criteria (SIOPEL-6). Among patients aged 7–18 years, hearing loss rates were even lower at 19% (ASHA) and 14.3% (Brock).
Pharmacokinetic analyses demonstrated no reduction in cisplatin exposure, and the study found no evidence of adverse interaction affecting antitumor activity. The overall tumor response rate of approximately 95% indicates that PEDMARK® does not interfere with cisplatin’s therapeutic effect.
“The STS-J01 findings add compelling support to the global clinical evidence base for PEDMARK®. Seeing such low rates of hearing loss in a real-world, investigator-initiated setting in Japan reinforces the consistency and magnitude of PEDMARK®’s protective effect, which has now been demonstrated across multiple continents, tumor types and clinical settings. Importantly, the high tumor response rate and the pharmacokinetic data show that PEDMARK® does not interfere with how cisplatin works; by six hours, the active platinum is already bound and inactive. This is a critical and highly reassuring finding for physicians, families and regulators alike.”
–Pierre S. Sayad, PhD, M.S., Chief Medical Officer of Fennec Pharmaceuticals
PEDMARK® was well tolerated. Across more than 200 treatment-emergent adverse events reported, none were attributed to PEDMARK®.
“For decades in Japan, we have witnessed the profound and lifelong burden of cisplatin-induced hearing loss among the children and young adults,” said Eiso Hiyama, M.D., lead investigator and professor in the Department of Pediatric Surgery at Hiroshima University Hospital. “These encouraging results from the first large-scale pediatric and adolescent and young adults (AYA) trial in Japan demonstrate that PEDMARK® can protect hearing without compromising cisplatin’s efficacy or introducing any concerning side effects. As a clinician, and with the current unmet medical need of cancer patients in Japan, these findings give me confidence in the effectiveness and safety of PEDMARK® which may offer patients the chance for both survival and preserved quality of life.”
Fennec intends to pursue registration in Japan and is exploring potential partnering or licensing opportunities for PEDMARK®. Full results from the study will be shared in a future scientific presentation and submitted for publication in a peer-reviewed journal.
About the STS-J01 Study
STS-J01 is a Phase 2/3, investigator-initiated, open-label, single-arm clinical trial designed to evaluate PEDMARK® for the prevention of cisplatin-induced ototoxicity. The study enrolled 33 patients: 27 children ages 3–18 years (primary cohort) and 6 infants aged ≥1 month to <3 years (exploratory cohort). All patients had localized solid tumors, including neuroblastoma, hepatoblastoma, germ cell tumors, bone and soft tissue sarcomas, medulloblastoma and atypical teratoid rhabdoid tumors. PEDMARK® was administered intravenously six hours after cisplatin, with dosing adjusted by body weight. The primary endpoint was incidence of hearing impairment in the 3–18 cohort using ASHA criteria. Secondary endpoints included safety, antitumor efficacy, pharmacokinetics, and hearing outcomes assessed by Brock grading. Exploratory endpoints included longitudinal audiometric follow-up and evaluation of surrogate hearing measures.
About Cisplatin-Induced Ototoxicity
Cisplatin and other platinum-based chemotherapies have improved survival outcomes for multiple solid tumors but often cause permanent, irreversible hearing loss known as ototoxicity.i Studies estimate that 60–90% of patients treated with cisplatin may develop some degree of hearing loss, depending on dose and cumulative exposure.ii Survivors may require lifelong hearing aids or cochlear implants, which do not restore natural hearing and may carry substantial long-term costs.iii Ototoxicity can impact speech and language development, learning, social-emotional health, career potential and overall independence.iv,v Despite clinical guidelines, audiologic monitoring remains underutilized in several cancer care settings.
PEDMARK® (sodium thiosulfate injection)
PEDMARK® is the first and only FDA-approved therapy indicated to reduce the risk of ototoxicity associated with cisplatin treatment in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors. PEDMARK® is provided as a ready-to-use, single-dose intravenous formulation. It is also recommended for the adolescent and young adult (AYA) population by the National Comprehensive Cancer Network (NCCN) with a 2A endorsement.
Approximately 500,000 patients in the United States are diagnosed annually with cancers potentially treated with platinum-based chemotherapy.vi,vii Before PEDMARK®’s approval, no preventive therapeutic options existed for cisplatin-related hearing loss. Clinical studies have shown that cancer survivors with treatment-related hearing loss experience significantly reduced quality of life compared with survivors without hearing impairment.viii,ix
Indications, Limitations of Use & Important Safety Information
Indications and Usage
PEDMARK® (sodium thiosulfate injection) is indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors.
Limitations of Use
The safety and efficacy of PEDMARK have not been established when administered following cisplatin infusions longer than 6 hours. PEDMARK may not reduce the risk of ototoxicity when administered following longer cisplatin infusions, because irreversible ototoxicity may have already occurred.
Important Safety Information
PEDMARK is contraindicated in patients with history of a severe hypersensitivity to sodium thiosulfate or any of its components.
Hypersensitivity reactions occurred in 8% to 13% of patients in clinical trials. Monitor patients for hypersensitivity reactions. Immediately discontinue PEDMARK and institute appropriate care if a hypersensitivity reaction occurs. Administer antihistamines or glucocortorticoids before each subsequent administration of PEDMARK. PEDMARK may contain sodium sulfite; patients with sulfite sensitivity may have hypersensitivity reactions, including anaphylactic symptoms and life-threatening asthma episodes.
PEDMARK is not indicated for use in pediatric patients under 1 month of age due to the increased risk of hypernatremia, or in pediatric patients with metastatic cancers.
Hypernatremia occurred in 12–26% of patients in clinical trials. Hypokalemia occurred in 15–27% of patients. Monitor serum sodium and potassium at baseline and as clinically indicated. Withhold PEDMARK in patients with baseline serum sodium greater than 145 mmol/L.
Administer antiemetics prior to each PEDMARK dose. Provide supportive care as needed.
The most common adverse reactions in SIOPEL-6 were vomiting, nausea, decreased hemoglobin, and hypernatremia. The most common adverse reaction in COG ACCL0431 was hypokalemia.
Please see full Prescribing Information for PEDMARK® at: www.PEDMARK.com
About Fennec Pharmaceuticals
Fennec Pharmaceuticals Inc. is a specialty pharmaceutical company focused on addressing ototoxicity in cancer patients receiving cisplatin-based chemotherapy. PEDMARK® received FDA approval in 2022 and European Commission and U.K. approvals in 2023 under the brand name PEDMARQSI®. In 2024, Fennec entered into an exclusive licensing agreement with Norgine Pharmaceuticals Ltd. for commercialization of PEDMARQSI® in Europe, the U.K., Australia and New Zealand. PEDMARK® and PEDMARQSI® benefit from regulatory exclusivity and patent protection extending through 2039.
References:
i Rybak L. Curr Opin Otolaryngol Head Neck Surg. 2007;15:364–369.
ii Langer T et al. Trends Pharmacol Sci. 2013;34(8):458–469.
iii Landier W. Cancer. 2016;122(11):1647–1658.
iv Clemens E et al. Lancet Oncol. 2019;20(1):e29–e41.
v Bass JK et al. Pediatr Blood Cancer. 2016;63(7):1152–1162.
vi Chattaraj A et al. JCO Oncol Pract. 2023;19.
vii Freyer DR et al. Lancet Oncol. 2017;18(1):63–74.
viii Rajput K et al. Int J Pediatr Otorhinolaryngol. 2020;138:110401.
ix Bass JK et al. Pediatr Blood Cancer. 2016;63(7):1152–1162.
