8-K: Fennec PEDMARK Japan Trial Success for Hearing Loss

Fennec Pharmaceuticals announced positive topline results from a Phase 2/3 clinical trial in Japan for PEDMARK, significantly reducing cisplatin-induced hearing loss in pediatric cancer patients.

Summary

• Fennec Pharmaceuticals Inc. announced positive topline results from the investigator-initiated Phase 2/3 STS-J01 clinical trial evaluating PEDMARK (sodium thiosulfate injection) in Japan.
• The trial assessed PEDMARK for the reduction of cisplatin-induced ototoxicity in pediatric and adolescent and young adult (AYA) patients with non-metastatic solid tumors.
• The study, which enrolled 27 patients in the primary cohort (3-18 years), met its primary endpoint.
• Data showed that 16-24% of evaluable patients treated with PEDMARK experienced hearing loss, compared to 56-63% in cisplatin-only arms of previous pivotal Phase 3 trials (ACCL0431 and SIOPEL-6).
• Among the largest subgroup of patients aged 7-18 years, hearing loss occurred in only 14.3-19%.
• Pharmacokinetic analyses demonstrated no reduction in cisplatin exposure, and there was no evidence of adverse interaction or attenuation of antitumor activity.
• The overall tumor response rate was approximately 95%, confirming PEDMARK does not interfere with cisplatin's antitumor activity.
• PEDMARK was well-tolerated in the study, with none of the more than 200 reported treatment-emergent adverse events attributed to PEDMARK.

Sentiment

Score: 9

Explanation: The filing reports highly positive clinical trial results for PEDMARK in Japan, demonstrating significant efficacy in reducing hearing loss without compromising cancer treatment, and good tolerability. This expands the market potential and reinforces the drug's global evidence base.

Positives

• Significant reduction in cisplatin-induced hearing loss (16-24% with PEDMARK vs. 56-63% historically) in pediatric and AYA patients.
• PEDMARK demonstrated no interference with cisplatin's antitumor activity, maintaining an approximate 95% clinical response rate.
• The drug was well-tolerated in the study, with no treatment-emergent adverse events attributed to PEDMARK.
• The findings add compelling support to the global clinical evidence base for PEDMARK, reinforcing its protective effect across multiple continents, tumor types, and clinical settings.
• Addresses a significant unmet medical need for cancer patients in Japan, offering a chance for both survival and preserved quality of life.

Risks

• Regulatory and guideline developments may change.
• Scientific data and/or manufacturing capabilities may not be sufficient to meet regulatory standards or obtain required regulatory clearances or approvals.
• Clinical results may not be replicated in actual patient settings.
• Unforeseen global instability, including political instability, or instability from an outbreak of pandemic or contagious disease.
• Protection offered by the company's patents and patent applications may be challenged, invalidated, or circumvented by its competitors.
• The available market for the company's products will not be as large as expected.
• The company's products will not be able to penetrate one or more targeted markets.
• Revenues will not be sufficient to fund further development and clinical studies.
• Inability to obtain necessary capital when needed on acceptable terms or at all.
• The company may not meet its future capital requirements in different countries and municipalities.

Future Outlook

Fennec Pharmaceuticals intends to pursue registration for PEDMARK in Japan and will explore partnering or licensing opportunities based on these positive results. Full results from the study will be shared in a future scientific presentation and submitted for publication in a peer-reviewed journal.

Management Comments

• "Seeing such low rates of hearing loss in a real-world, investigator-initiated setting in Japan reinforces the consistency and magnitude of PEDMARKs protective effect, which has now been demonstrated across multiple continents, tumor types and clinical settings." Pierre S. Sayad, PhD, M.S., chief medical officer of Fennec Pharmaceuticals.
• "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.
• "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 cisplatins efficacy or introducing any concerning side effects." Eiso Hiyama, M.D., lead investigator and professor in the Department of Pediatric Surgery at Hiroshima University Hospital.
• "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." Eiso Hiyama, M.D.

Industry Context

Cisplatin and other platinum-based chemotherapies are crucial for treating solid tumors but frequently cause permanent, irreversible hearing loss in 60-90% of patients. PEDMARK, as the first and only FDA-approved therapy to reduce this risk in pediatric patients, addresses a significant global unmet medical need. The positive results from the Japan trial further solidify its position and expand its potential market, offering a vital supportive care option in oncology.

Comparison to Industry Standards

• PEDMARK's 16-24% hearing loss rate in the STS-J01 trial compares favorably to the 56-63% hearing loss rates observed in cisplatin-only arms of previous pivotal Phase 3 trials (ACCL0431 and SIOPEL-6).
• PEDMARK is the first and only U.S. Food and Drug Administration (FDA) approved therapy indicated to reduce the risk of ototoxicity associated with cisplatin treatment in pediatric patients, establishing a new benchmark for preventative care.
• The product is recommended for the adolescent and young adult (AYA) population by the National Comprehensive Cancer Network (NCCN) with a 2A endorsement, indicating strong clinical support.

Stakeholder Impact

• Shareholders: Positive impact due to expanded market potential in Japan, reinforced clinical evidence, and potential for new partnerships/licensing, which could drive future revenue growth.
• Patients (Pediatric/AYA): Significant positive impact by offering a treatment to prevent permanent, irreversible hearing loss while undergoing life-saving cisplatin chemotherapy, thereby improving their long-term quality of life.
• Physicians/Regulators: Reassurance regarding PEDMARK's efficacy and safety, particularly its non-interference with cisplatin's antitumor activity, which is crucial for patient care decisions and regulatory approvals.
• Employees: Potential for increased job security and growth opportunities as the company expands its market reach and commercialization efforts.

Next Steps

• Pursue registration for PEDMARK in Japan.
• Explore partnering or licensing opportunities for PEDMARK in Japan.
• Share full study results in a future scientific presentation.
• Submit full study results for publication in a peer-reviewed journal.

Key Dates

Recommendation

The positive topline results from the Phase 2/3 trial in Japan significantly de-risk the expansion of PEDMARK into a new major market. The demonstrated efficacy (significant reduction in hearing loss) and safety profile, coupled with no interference with the primary cancer treatment, are highly favorable. The company's intent to pursue registration and explore partnerships in Japan indicates a clear path to commercialization and revenue growth. This news strengthens the global commercialization prospects for PEDMARK, which is already FDA and EC approved, and should positively impact the company's valuation.

Keywords

Fennec Pharmaceuticals, PEDMARK, sodium thiosulfate, cisplatin, ototoxicity, hearing loss, pediatric cancer, solid tumors, clinical trial, Japan, FDA approved, oncology, specialty pharmaceutical