Sensorion Completes Patient Enrollment in NOTOXIS Phase 2a Clinical Trial of SENS-401 for Cisplatin-Induced Ototoxicity Prevention
Sensorion, a pioneering clinical-stage biotechnology company focused on the development of innovative therapies for hearing loss disorders, has announced the completion of patient enrollment in its NOTOXIS Proof of Concept (POC) Phase 2a clinical trial. The trial evaluates SENS-401, an investigational therapy aimed at preventing Cisplatin-Induced Ototoxicity (CIO), a significant and often irreversible side effect of cisplatin-based chemotherapy.
Overview of the NOTOXIS Phase 2a Trial
The NOTOXIS trial (ClinicalTrials.gov ID: NCT05628233) is a multicenter, randomized, controlled, open-label Phase 2a study designed to assess the efficacy and safety of SENS-401 in adult patients undergoing cisplatin-based chemotherapy for neoplastic diseases. The study aims to determine whether SENS-401 can provide otoprotective benefits without compromising the chemotherapeutic efficacy of cisplatin.
A total of 80 patients were screened for participation, with 47 successfully randomized into the study. Of these, 24 patients were assigned to receive SENS-401, while 23 were placed in the control group. The trial protocol specifies that patients receiving SENS-401 take 43.5 mg of the oral agent twice daily over a period extending up to 23 weeks. The treatment regimen includes:
- One week of administration before initiating cisplatin chemotherapy.
- Continuation of therapy throughout the entire chemotherapy course, estimated to last up to 18 weeks.
- An additional four weeks of treatment following the completion of chemotherapy.
The primary endpoint of the trial focuses on changes in pure tone audiometry (PTA) (measured in decibels) from baseline to four weeks after the final dose of cisplatin. Secondary endpoints include assessments of safety, changes in speech discrimination in both noise and quiet environments, and evaluations using the Tinnitus Handicap Inventory (THI) scale.
Preliminary Findings and Implications
Sensorion previously presented preliminary data from the NOTOXIS study at the World Congress of Audiology in Paris in September 2024. The analysis, which included data from 16 patients, suggested that SENS-401 exhibits otoprotective effects at cisplatin doses exceeding 300 mg/m². Additionally, the therapy demonstrated a favorable safety profile, with no major adverse effects reported in the early-stage analysis.
Given the severity and prevalence of cisplatin-induced hearing loss, these early findings are promising. Sensorion expects to release topline results from the full Phase 2a NOTOXIS study by the end of the second half of 2025.
Significance of SENS-401 in Addressing Cisplatin-Induced Ototoxicity
Cisplatin and other platinum-based chemotherapy agents are widely used in oncology for the treatment of various cancers, including testicular, ovarian, lung, and bladder cancers. However, one of the most severe and often permanent adverse effects of these treatments is ototoxicity. Hearing loss resulting from cisplatin therapy affects an estimated 40% to 60% of adult patients and an even higher percentage of pediatric patients.
Ototoxicity is particularly detrimental because it is irreversible, significantly impacting a patient’s quality of life. For children, hearing loss can interfere with language development and learning, leading to lifelong challenges. For adults, it can contribute to social isolation, cognitive decline, and overall reduced well-being.
Currently, there are no FDA-approved treatments to prevent or mitigate CIO, highlighting a major unmet medical need. If SENS-401 proves to be effective, it could offer a groundbreaking solution to preserve hearing in cancer patients without compromising their treatment outcomes.
Mechanism of Action and Therapeutic Potential of SENS-401
SENS-401 is a small molecule drug designed to protect the inner ear from damage associated with chemotherapy, trauma, or other ototoxic insults. It exerts its protective effects by modulating pathways involved in cochlear cell survival and reducing inflammation and oxidative stress, both of which contribute to hearing loss following cisplatin exposure.
By preserving cochlear function, SENS-401 has the potential not only to maintain hearing thresholds but also to improve speech discrimination and reduce the severity of tinnitus, which is another common side effect of ototoxic chemotherapy.
Statements from Sensorion Leadership
Dr. Géraldine Honnet, Chief Medical Officer of Sensorion, emphasized the importance of the NOTOXIS trial as a crucial step in developing an effective therapy for CIO:
“Today’s announcement marks a key development milestone for SENS-401, our small molecule therapeutic candidate that has the potential to mitigate the irreversible and permanent hearing loss frequently seen in adults following cisplatin-based chemotherapies without interfering with cisplatin efficacy. I would like to thank the patients and physicians involved in the trial for their trust and commitment. The preliminary results are encouraging, and I look forward to assessing the full data of all patients treated in NOTOXIS and communicating the topline results of this trial by the end of 2025.”
Future Directions and Market Potential
Sensorion’s ongoing research into SENS-401 represents a critical advancement in the field of otoprotective therapeutics. If the Phase 2a trial confirms the preliminary findings, the company is likely to pursue further clinical development, potentially advancing to a pivotal Phase 3 trial in the near future.
The global market for hearing loss treatments and prevention is expanding, driven by the growing recognition of auditory health as a key component of overall well-being. The unmet need for effective CIO treatments presents a significant commercial opportunity for Sensorion, positioning SENS-401 as a potential first-in-class therapy in a field with limited options.
Beyond CIO, Sensorion is also exploring additional indications for SENS-401, including applications in sudden sensorineural hearing loss (SSNHL) and cochlear implantation. These additional avenues further highlight the broad therapeutic potential of the drug.
