MONTPELLIER, FRANCE – Sensorion (FR0012596468 – ALSEN), a clinical-stage biotechnology company focused on developing novel therapies to treat and prevent hearing loss disorders, has announced encouraging preliminary data from the first patient cohort of its ongoing Phase 1/2 Audiogene clinical trial. The trial evaluates SENS-501, an investigational gene therapy candidate targeting a specific form of congenital deafness caused by mutations in the OTOF (otoferlin) gene.
The data, released today, suggest a favorable safety profile and show early signs of auditory response in at least one patient receiving the low dose of SENS-501. These findings mark a significant milestone in Sensorion’s mission to bring novel genetic therapies to individuals with severe-to-profound congenital hearing loss.
Promising Early Signs in Toddlers with OTOF-Related Hearing Loss
The Audiogene trial is being conducted in infants and toddlers between the ages of 6 and 31 months, all of whom were naïve to cochlear implants at the time of the gene therapy injection. In total, five children have been treated to date, with no serious adverse events observed. These results suggest that SENS-501 is not only safe and well-tolerated at the current dose but also holds the potential to restore auditory function in young children with OTOF mutations.
Among the three patients treated in the first cohort at the lowest dose (1.5E11 vector genomes per ear), one toddler—identified as Patient 3—demonstrated measurable improvements in hearing after three months.
Three-month data from the Patient 3 include:
- Positive ABR responses at two frequencies, with the best frequency reaching 70 dB.
- Improvement of hearing levels across two speech frequencies with best frequency reaching 90 dB level, per
PTA. - Meaningful changes in responses to sounds and voices as reported by the parents with an IT-MAIS score
increase of 16 points (145% relative improvement from baseline), and met expected auditory milestones
based on an age-based parent questionnaire and according to the patient’s age (LittlEARS)
Parental observations reinforced the clinical data. According to parent-reported outcome measures, including the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS), Patient 3’s score improved by 16 points, representing a 145% relative increase from baseline. The child also met age-appropriate auditory milestones as captured by the LittlEARS questionnaire.
“This highly innovative therapy showed a good safety profile, and the onset of early auditory responses in Patient 3 is very encouraging,” said Professor Catherine Birman, ENT surgeon and senior staff specialist at the Children’s Hospital at Westmead, Australia.
“Treating children under 31 months of age, naïve to cochlear implants, is a much-needed undertaking, as restoring hearing in the first three years of childhood has the potential to result in de novo language acquisition.”
The Science Behind SENS-501
SENS-501 is a dual AAV (adeno-associated virus) vector-based gene therapy designed to deliver a healthy copy of the OTOF gene to the inner ear. Mutations in this gene are among the most common causes of autosomal recessive non-syndromic hearing loss and typically result in congenital, severe-to-profound deafness.
Unlike sensorineural hearing loss stemming from outer hair cell damage, OTOF-related hearing loss originates from dysfunction in synaptic transmission within the inner ear. Because the sensory hair cells remain intact, it is considered an ideal target for genetic therapies that aim to restore the neural signal pathway rather than regenerate hair cells.
The dual-vector strategy employed by Sensorion allows the large OTOF gene, which exceeds the packaging capacity of single AAV vectors, to be effectively delivered to target cells. This technical innovation overcomes a key barrier in gene therapy for hearing loss and sets the stage for therapeutic interventions in other genetic forms of deafness.
Advancing Toward Higher Dose and Expanded Enrollment
With the successful treatment and follow-up of Cohort 1, Sensorion is moving forward with the second patient cohort, which will receive a higher dose of SENS-501—4.5E11 vector genomes per ear. According to the company, recruitment for this next group is nearly complete, and patient follow-up is underway. The second cohort will provide additional insight into the dose-response relationship and safety at an increased dosage.
Following the dose-escalation phase, the trial is expected to proceed to a dose-expansion stage to further validate efficacy and refine treatment protocols.
“This is an important step forward not only for Sensorion but for the entire field of genetic hearing restoration. We are encouraged by these early signals and look forward to advancing SENS-501 as part of our broader mission to address genetic hearing disorders through science-driven innovation.”
–Sensorion CEO, Nawal Ouzren
The Audiogene trial is being conducted in collaboration with world-class institutions including Institut Pasteur and Necker Enfants Malades Hospital in Paris. The clinical lead is Professor Natalie Loundon, MD, who has long been involved in pediatric auditory research and cochlear implantation. This trial is unique in that it is treating children who have not previously received cochlear implants, preserving the possibility of native hearing function development rather than reliance on external devices.
A Collaborative Effort: RHU AUDINNOVE Consortium
The SENS-501 program is supported by the RHU AUDINNOVE consortium, a public-private partnership bringing together leading stakeholders in auditory science. Members of the consortium include Sensorion, Institut Pasteur, Necker Hospital, and Fondation pour l’Audition. The initiative also benefits from partial funding from the French National Research Agency, underscoring the growing recognition of genetic hearing loss as a priority area in medical research.
“Treating congenital deafness at the genetic level holds tremendous promise,” said Professor Natalie Loundon. “Our goal is not just to stabilize hearing loss but to enable real, functional recovery of hearing in very young children, when the brain is most plastic and language acquisition is still developing.”
The Audiogene trial represents one of the first clinical efforts globally to explore otoferlin gene therapy in a pediatric population. While other investigational gene therapies are in development, SENS-501 is among the most advanced in targeting OTOF-related hearing loss specifically in infants and toddlers.
Looking Ahead
Sensorion expects to provide further updates on the second cohort once follow-up data have reached a sufficient level of maturity. The company also plans to explore potential regulatory pathways and partnerships for accelerating the development and commercialization of SENS-501, depending on trial outcomes.
If early signals of hearing recovery continue in the second cohort or expand to additional patients, it could mark a transformative step for thousands of children born with OTOF mutations each year.
For families affected by congenital deafness, these advances bring renewed hope. As Professor Birman noted, “The earlier we can intervene, the greater the chance for normal auditory and language development. This research could have life-changing implications.”
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. OTOF-GT 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 clinical-stage small molecule programs for the treatment and prevention of hearing loss disorders.
Sensorion’s clinical-stage portfolio includes one Phase 2 product: SENS-401 (Arazasetron) progressing in a planned Phase 2 proof of concept clinical study of SENS-401 in Cisplatin-Induced Ototoxicity (CIO) and, with partner Cochlear Limited, in a study of SENS-401 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.
Source: Sensorion
