Sensorion Finishes Enrolling Patients in Second Cohort of Its Phase 1/2 Trial for Congenital Deafness Gene Therapy SENS-501

Sensorion has completed patient enrollment for the second cohort of its phase 1/2 Audiogene clinical trial (NCT06370351) evaluating SENS-501 (OTOF-GT), a gene therapy candidate for otoferlin gene (OTOF)-related congenital deafness, one of the most common forms of congenital deafness.^1,2 The announcement marks a key milestone in the dose-escalation study designed to assess the safety and efficacy of intracochlear gene therapy in infants and toddlers.

The second cohort includes 3 patients aged 6 to 31 months who received a unilateral dose of 4.5x10¹¹ vg/vector/ear of SENS-501, a 3-fold increase from the 1.5x10¹¹ vg/vector/ear dose administered in the first cohort. According to Sensorion, all 6 patients across both cohorts tolerated the surgical procedure and gene therapy administration well, with no serious adverse events reported.

Notably, early signs of hearing improvement were observed in a patient from the first cohort, who was treated at 11 months of age and evaluated 3 months posttreatment. These preliminary findings support continued investigation into the safety and therapeutic potential of SENS-501. There are currently no approved curative therapies for the condition.

“I am thrilled we have successfully completed the patient enrollment of the second cohort in Audiogene’s phase 1/2 gene therapy trial,” principal investigator Natalie Loundon, MD, director of the Center for Research in Pediatric Audiology, pediatric otolaryngologist and head and neck surgeon, Necker Enfants Malades, AP-HP, in Paris, France, said in a statement.¹ “ The good tolerability of patients to SENS-501 so far and the preliminary positive data from the first cohort are very encouraging first steps for the continuation of this trial that has the potential to address a global significant unmet medical need.”

Audiogene is the first gene therapy trial to focus exclusively on infants and toddlers with congenital deafness because of OTOF mutations who are naive to cochlear implants. The otoferlin protein is large and is delivered to the inner ear using 2 adeno-associated virus (AAV) vectors and assembled in place. Patients with OTOF mutations suffer from severe to profound sensorineural prelingual nonsyndromic hearing loss. The trial aims to restore hearing and support normal speech development during the critical early window of brain plasticity. In addition to evaluating safety and auditory function via auditory brainstem response (ABR), the study also assesses the usability and technical performance of the custom intracochlear delivery system.^1,2

The second cohort enrollment followed data monitoring committee (DMC) clearance after safety review of the first 3 patients, allowing the study to progress to the higher dose level. The first cohort showed a favorable safety profile, with no serious adverse events and early behavioral improvements reported in the treated children. These findings supported initiation and completion of dosing in the second cohort, which is now fully enrolled and treated. The trial continues to evaluate both the gene therapy SENS-501 and a custom intracochlear delivery system developed by EVEON, with a total target enrollment of approximately 12 patients across sites in France and Australia.³

SENS-501 is designed to deliver a functional copy of the OTOF gene to the inner ear’s hair cells. Mutations in OTOF disrupt the conversion of sound into electrical signals, leading to profound hearing loss from birth. Otoferlin deficiency is responsible for up to 8% of all cases of congenital hearing loss, with approximately 20,000 people affected in the United States and Europe. SENS-501 aims to restore gene function and enable natural hearing and speech acquisition. The therapy is being developed under the RHU AUDINNOVE consortium, supported in part by the French National Research Agency.¹^,⁴

“I look forward to advancing this innovative and unique program to its next steps, notably with the planned DMC meeting, and to providing an update as soon as the data have sufficiently matured,” Nawal Ouzren, chief executive officer of Sensorion, said in a statement.¹ “On behalf of my colleagues, I would like to extend gratitude to the patients' families for their trust, as well as all the healthcare professionals involved in this clinical trial.”

Sensorion is advancing a pipeline of gene therapies for hereditary hearing loss in partnership with Institut Pasteur, including SENS-501 and GJB2-GT for GJB2-related hearing loss. In parallel, the company is developing SENS-401, a small molecule therapy in phase 2 trials for various acquired forms of hearing loss.

REFERENCES
1. Sensorion completes patient enrollment of the second cohort in Audiogene phase 1/2 gene therapy clinical trial. News release. Firstwordpharma.com. July 29, 2025. Accessed August 7, 2025. https://firstwordpharma.com/story/5984441
2. Rodríguez-Ballesteros M, Reynoso R, Olarte M, et al. A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy. Hum Mutat. 2008;29(6):823-831. doi:10.1002/humu.20708
3. Stansfield N. Sensorion makes progress in trial for OTOF hearing loss gene therapy. CGTLive. February 21, 2025. Accessed August 7, 2025. https://www.cgtlive.com/view/sensorion-progress-trial-otof-hearing-loss-gene-therapy
4. Rodríguez-Ballesteros M, Reynoso R, Olarte M, et al. Sensorion receives orphan drug designation for OTOF-GT for the treatment of otoferlin gene-mediated hearing loss from the US Food and Drug Administration. Hum Mutat. 2008;29(6):823-831. doi:https://doi.org/10.1002/humu.20708