Sensorion's Gene Therapy SENS-501 Shows Early Efficacy Signals in Pediatric Congenital Deafness Trial
核心洞察
Sensorion's Data Monitoring Committee found no safety concerns and approved continuation of the Audiogene Phase 1/2 trial for SENS-501 gene therapy targeting OTOF (搜索) gene mutations.
Two of three patients in the second cohort demonstrated early hearing improvements by Month 3, with behavioral thresholds of approximately 60-70 dB HL at best-performing frequencies.
The trial targets infants aged 6-31 months with otoferlin-mediated congenital deafness (搜索), aiming to restore hearing during critical brain plasticity periods before cochlear implantation.
Sensorion announced that its Data Monitoring Committee (DMC) has raised no safety concerns and supports continuation of the Audiogene Phase 1/2 clinical trial evaluating SENS-501, a gene therapy targeting congenital deafness (搜索) caused by mutations in the OTOF (搜索) (otoferlin (搜索)) gene. The committee's December 4th review found good procedural tolerance with no serious adverse events or side effects reported across both trial cohorts.
The French biotechnology company reported early efficacy signals in the second cohort, where two of three treated patients demonstrated directional improvements in hearing by Month 3 on pure-tone audiometry. Patient 4 achieved a behavioral threshold of approximately 60 dB HL at the best-performing frequency, while Patient 5 demonstrated approximately 70 dB HL at the best-performing frequency.
Trial Design and Patient Population
The Audiogene trial evaluates the safety, tolerability and efficacy of intra-cochlear administration of SENS-501 in pediatric patients aged 6 to 31 months. The study specifically targets infants who have not yet received cochlear implants, allowing researchers to assess SENS-501 as monotherapy during the critical early window of brain plasticity.
The trial comprises two sequential dose-escalation cohorts with unilateral injection to enable clear assessment of hearing restoration kinetics. Cohort 2, which completed enrollment in July 2025, included three patients who received dose 2 of SENS-501 (4.5E11 vg/vector/ear). The study also evaluates the usability and technical performance of Sensorion's injection system.
"Treating otoferlin-mediated congenital deafness (搜索) before cochlear implantation and during heightened neural plasticity is essential to fully evaluate the potential of gene therapy as a monotherapy," said Nawal Ouzren, Chief Executive Officer of Sensorion. "We will continue to generate rigorous and comprehensive data to guide development decisions for this important patient population."
Gene Therapy Mechanism and Development
SENS-501 (OTOF-GT) uses adeno-associated virus (AAV) vector technology to deliver functional copies of the OTOF (搜索) gene directly into hair cells of the inner ear. The otoferlin (搜索) gene plays a crucial role in transmitting auditory signals between hair cells and the auditory nerve. When defective, individuals are born with severe to profound hearing loss (搜索).
The therapy aims to restore the normal process of converting sound into electrical signals, potentially enabling patients to regain hearing ability. The OTOF (搜索) gene was discovered in 1999 at the Institut Pasteur by Prof. Christine Petit's team, who also unraveled the pathophysiology of the corresponding deafness (DFNB9).
Clinical Development Timeline
Sensorion plans to review six-month efficacy data and communicate results during Q1 2026 once the dataset reaches sufficient maturity. Follow-up continues to assess the durability of observed effects and potential for further clinically meaningful functional gains.
The Audiogene trial's primary endpoint focuses on safety in the dose escalation phase, while auditory brainstem response (ABR) will serve as the primary efficacy endpoint in the expansion phase. By targeting the first years of life when brain plasticity is optimal, the study aims to maximize chances for young children with pre-linguistic hearing loss (搜索) to acquire normal speech and language.
Broader Pipeline and Partnerships
SENS-501 represents one of two gene therapy programs in Sensorion's pipeline targeting hereditary monogenic forms of deafness, developed through strategic collaboration with the Institut Pasteur. The company's second gene therapy, GJB2 (搜索)-GT, targets hearing loss (搜索) related to GJB2 gene mutations.
The SENS-501 program was developed within the RHU AUDINNOVE consortium, comprising Sensorion, Necker Enfants Malades Hospital, Institut Pasteur, and Fondation pour l'Audition. The project receives partial financing from the French National Research Agency through the "investing for the future" program.