PEDMARK Shows Significant Reduction in Cisplatin-Induced Hearing Loss in Japanese Pediatric Cancer Study
Key Insights
A Phase 2/3 clinical trial in Japan demonstrated that PEDMARK significantly reduced cisplatin-induced hearing loss (search) in pediatric cancer patients, with only 16-24% experiencing ototoxicity (search) compared to 56-63% in historical controls.
The study confirmed PEDMARK's safety profile with no interference in cisplatin's antitumor activity, achieving a 95% tumor response rate while protecting hearing function.
These positive results support Fennec Pharmaceuticals' plans to pursue regulatory approval in Japan and explore licensing partnerships for the first FDA-approved ototoxicity (search) prevention therapy.
Fennec Pharmaceuticals announced positive topline results from an investigator-initiated Phase 2/3 clinical trial evaluating PEDMARK (sodium thiosulfate injection) in Japan, demonstrating significant protection against cisplatin-induced hearing loss (search) in pediatric and adolescent cancer patients. The STS-J01 study met its primary endpoint, showing substantially lower rates of ototoxicity (search) compared to historical controls while maintaining the chemotherapy's cancer-fighting effectiveness.
Study Results Show Dramatic Reduction in Hearing Loss
The trial enrolled 27 patients aged 3-18 years in the primary cohort and 6 patients in exploratory cohorts, all with localized, non-metastatic solid tumors. Results showed that only 24% and 16% of evaluable patients treated with PEDMARK experienced hearing loss as assessed by American Speech-Language-Hearing Association (ASHA) criteria and Brock grade scaling, respectively.
These rates represent a significant improvement compared to cisplatin-only treatment arms from PEDMARK's pivotal Phase 3 trials, where 56% of children developed clinically significant hearing loss using ASHA criteria (ACCL0431) and 63% developed hearing impairment defined as Brock Grade ≥1 (SIOPEL-6). Among the largest subgroup of patients aged 7-18 years, hearing loss occurred in only 19% (ASHA) and 14.3% (Brock).
Preserved Antitumor Efficacy Confirms Safety Profile
Pharmacokinetic analyses demonstrated no reduction in cisplatin exposure, with no evidence of adverse interaction or attenuation of antitumor activity. The overall tumor response rate of approximately 95% confirms that PEDMARK does not interfere with cisplatin's cancer-fighting properties.
"The STS‑J01 findings add compelling support to the global clinical evidence base for PEDMARK," said Pierre S. Sayad, PhD, M.S., chief medical officer of Fennec Pharmaceuticals. "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."
Clinical Significance for Japanese Patients
The study addressed a significant unmet medical need in Japan, where cisplatin-induced hearing loss (search) has been a longstanding challenge in pediatric oncology. Lead investigator Eiso Hiyama, M.D., professor in the Department of Pediatric Surgery at Hiroshima University Hospital, emphasized the clinical impact of these findings.
"For decades in Japan, we have witnessed the profound and lifelong burden of cisplatin‑induced hearing loss among the children and young adults," Hiyama said. "These encouraging results from the first large-scale pediatric and adolescent and young adults trial in Japan demonstrate that PEDMARK can protect hearing without compromising cisplatin's efficacy or introducing any concerning side effects."
Safety and Tolerability Profile
PEDMARK was well-tolerated throughout the study. Across more than 200 treatment-emergent adverse events reported, none were attributed to PEDMARK administration. This safety profile aligns with previous clinical experience with the therapy.
Study Design and Patient Population
The STS-J01 trial was designed as a Phase 2/3, investigator-initiated, open-label, single-arm clinical study. Patients included those with various solid tumors including neuroblastoma (search), hepatoblastoma (search), germ cell tumors (search), bone and soft tissue sarcomas, medulloblastoma (search), and atypical teratoid rhabdoid tumors. PEDMARK was administered intravenously six hours after cisplatin infusion, with dosing adjusted by body weight.
Regulatory and Commercial Implications
Based on these positive results, Fennec Pharmaceuticals plans to pursue registration in Japan and explore partnering or licensing opportunities for PEDMARK in the Japanese market. The company noted that full results from the study will be shared in future scientific presentations and submitted for publication in peer-reviewed journals.
PEDMARK is currently the first and only FDA-approved therapy indicated to reduce the risk of ototoxicity (search) associated with cisplatin treatment in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors. The therapy has also received European Commission approval and is commercially available in the U.K. and Germany through a licensing agreement with Norgine Pharmaceuticals (search).