Sensorion Reports Promising Early Data from Phase 1/2 Audiogene Gene Therapy Trial
Sensorion (FR0012596468 – ALSEN), a clinical-stage biotechnology company focused on developing innovative therapies for hearing loss, has announced encouraging preliminary results from the first cohort of its Phase 1/2 clinical trial, Audiogene. The trial evaluates SENS-501, a gene therapy candidate designed to treat congenital deafness caused by mutations in the OTOF (otoferlin) gene.
Early Signs of Efficacy Observed in Young Patient
The Audiogene trial’s first cohort involved three infants and toddlers between the ages of 6 and 31 months, all of whom had not received cochlear implants before enrollment. Each patient received a low dose of SENS-501 (1.5E11 vg/vector/ear), a level selected to prioritize safety while representing the minimum effective dose identified in preclinical research.
Among the three patients in Cohort 1, Patient 3, aged 11 months at the time of treatment, exhibited early and measurable improvements in hearing function just three months after receiving the therapy. According to standardized assessments:
- Auditory Brainstem Response (ABR) testing indicated positive responses at two frequencies, with one reaching a 70 dB threshold.
- Pure Tone Audiometry (PTA) demonstrated hearing improvements at two speech-relevant frequencies, with the most sensitive frequency reaching 90 dB.
- Parent-reported outcomes showed meaningful changes in the child’s responsiveness to sounds and voices. The IT-MAIS (Infant-Toddler Meaningful Auditory Integration Scale) score rose by 16 points, reflecting a 145% relative improvement from baseline.
- Additionally, according to the LittlEARS auditory questionnaire, the child met age-appropriate auditory milestones.
These improvements are significant considering the patient received a low, safety-focused dose of SENS-501.
A Safe and Tolerable Procedure
In total, five patients have received SENS-501 across both cohorts to date. Sensorion confirmed that the gene therapy and its intracochlear delivery method were well tolerated, with no serious adverse events or significant side effects reported. The gene therapy was administered directly into the cochlea, and all procedures were uneventful.
This safety profile is crucial in the context of treating very young children, where medical interventions must be approached with the utmost caution.
Cohort 2 Nears Completion
Sensorion is currently completing recruitment for the second cohort of the Audiogene trial. This cohort is receiving a higher dose of SENS-501 (4.5E11 vg/vector/ear), three times the amount given to the first group. While the primary focus remains on safety and tolerability, this escalation may also provide more insight into the therapy’s potential efficacy.
The company plans to release additional data once the second cohort’s results mature, which will help guide decisions for subsequent development steps, including the design of a dose-expansion phase.
Expert Perspective: A Milestone in Pediatric Gene Therapy
Commenting on the preliminary results, Professor Catherine Birman, an ENT surgeon and otolaryngologist at the Children’s Hospital at Westmead, Australia, expressed enthusiasm for the early outcomes:
“I’m thrilled to report the preliminary Cohort 1 data of SENS-501 in the first infants and toddlers treated with this highly innovative therapy. Treatment with SENS-501 had a good safety profile, and the onset of early auditory responses observed in Patient 3 is very encouraging, especially given the very low dose administered.”
Professor Birman emphasized the importance of treating children within the first three years of life, when the brain’s plasticity is at its peak and the potential for language acquisition is greatest:
“Restoring hearing in early childhood has the potential to result in de-novo language acquisition. We thank Sensorion for their commitment to this patient population.”
About the Audiogene Clinical Trial
The Audiogene trial (ClinicalTrials.gov ID: NCT06370351) is part of Sensorion’s strategic collaboration with Institut Pasteur. The trial is being led by Professor Natalie Loundon, M.D., who serves as the Coordinating Investigator. Dr. Loundon is also the Director of the Center for Research in Pediatric Audiology and a Head and Neck Surgeon at Necker Enfants Malades Hospital in Paris, France.
Trial Design and Objectives
Audiogene is a Phase 1/2 trial with a dose-escalation and expansion design. The first two cohorts involve three patients each and are evaluating:
- Cohort 1: Low dose of SENS-501 (1.5E11 vg/vector/ear)
- Cohort 2: Higher dose of SENS-501 (4.5E11 vg/vector/ear)
Pending successful completion of these phases, the trial will proceed to a dose-expansion cohort using the optimal dose selected from the first two stages.
Unique Focus on a Homogeneous Pediatric Population
Audiogene is the first gene therapy trial targeting a uniquely homogeneous group of young pediatric patients (ages 6–31 months), all of whom are naive to cochlear implants at the time of enrollment. This restriction ensures that the therapeutic outcomes can be more directly attributed to SENS-501, unconfounded by previous interventions.
The trial’s primary goal in the dose-escalation phase is to evaluate safety and surgical feasibility. In the later dose-expansion phase, the main efficacy endpoint will be Auditory Brainstem Response (ABR) measured 12 months after gene therapy administration.
Addressing a Critical Unmet Need
Congenital deafness due to OTOF gene mutations represents a well-defined and genetically homogenous form of hearing loss, often referred to as auditory synaptopathy. Children with this condition are born deaf but typically have structurally intact cochleae and auditory nerves—making them strong candidates for gene therapy approaches that restore function at the cellular or molecular level.
Sensorion’s SENS-501 program aims to offer a one-time treatment that could significantly alter the developmental trajectory of affected children by restoring auditory input during a critical window of language development.
Looking Ahead
As Sensorion finalizes recruitment for Cohort 2 and awaits further clinical data, the early safety and efficacy signals from Cohort 1—particularly the promising hearing improvements in Patient 3—provide a foundation of hope for families affected by genetic hearing loss. The company’s cautious and methodical approach in addressing this vulnerable pediatric population sets the stage for potentially transformative outcomes in the years ahead.
Sensorion remains committed to transparency and plans to share more detailed updates as data matures from the ongoing Audiogene trial.
About SENS-501
SENS-501 (OTOF-GT) is an innovative gene therapy program developed to treat a specific form of congenital deafness linked to mutations in the OTOF (otoferlin) gene. This gene plays a key role in the transmission of auditory signals between the hair cells of the inner ear and the auditory nerve. When this gene is defective, affected individuals are born with severe to profound hearing loss.
The aim of SENS-501 (OTOF-GT) is to restore hearing by introducing a functional copy of the OTOF gene directly into hair cells via viral vector technology (AAV). This therapy aims to restore the normal process of converting sound into electrical signals, enabling patients to regain their hearing ability. Currently in the clinical research phase, this gene therapy program represents significant hope for families affected by this rare form of genetic deafness.
SENS-501 (OTOF-GT) embodies a commitment to scientific innovation in the field of hearing, with the potential to dramatically improve the quality of life of patients suffering from genetic deafness. This gene therapy for patients suffering from otoferlin deficiency has been developed in the framework of RHU AUDINNOVE, a consortium composed of Sensorion with the Necker Enfants Malades Hospital, the Institut Pasteur, and the Fondation pour l’Audition. The project is partially financed by the French National Research Agency, through the “investing for the future” program (ref: ANR-18-RHUS-0007).
The OTOF gene targeted by the Audiogene trial was discovered in 1999 at the Institut Pasteur, by Prof. Christine Petit’s team (Institut reConnect, Institut de l’Audition, Pasteur Institute), who also unraveled the pathophysiology of the corresponding deafness (DFNB9).
About Sensorion
Sensorion is a pioneering clinical-stage biotech company, which specializes in the development of novel therapies to restore, treat, and prevent hearing loss disorders, a significant global unmet medical need. Sensorion has built a unique R&D technology platform to expand its understanding of the pathophysiology and etiology of inner ear related diseases, enabling it to select the best targets and mechanisms of action for drug candidates.
It has two gene therapy programs aimed at correcting hereditary monogenic forms of deafness, developed in the framework of its broad strategic collaboration focused on the genetics of hearing with the Institut Pasteur. SENS-501 (OTOF-GT) currently being developed in a Phase 1/2 clinical trial, targets deafness caused by mutations of the gene encoding for otoferlin and GJB2-GT targets hearing loss related to mutations in GJB2 gene to potentially address important hearing loss segments in adults and children. The Company is also working on the identification of biomarkers to improve diagnosis of these underserved illnesses.
Sensorion’s portfolio also comprises programs of a clinical-stage small molecule, SENS-401 (Arazasetron), for the treatment and prevention of hearing loss disorders. Sensorion’s small molecule progresses in a Phase 2 proof of concept clinical study of SENS-401 in Cisplatin-Induced Ototoxicity (CIO) for the preservation of residual hearing. Sensorion, with partner Cochlear Limited, completed in 2024 a Phase 2a study of SENS-401 for the residual hearing preservation in patients scheduled for cochlear implantation. A Phase 2 study of SENS-401 was also completed in Sudden Sensorineural Hearing Loss (SSNHL) in January 2022.
www.sensorion.com
