Sensorion recently announced positive preliminary data from a Phase 1/2 clinical trial of its investigational gene therapy, SENS-501, for the treatment of congenital deafness associated with mutations in the OTOF (otoferrin) gene.
Results from the first cohort demonstrated that the therapy was safe and well-tolerated in infants and young children, with one 11-month-old infant demonstrating significant hearing improvement after just three months of treatment at the lowest dose.
"SENS-501 demonstrated a favorable safety profile and preliminary efficacy in the first infants treated, particularly at this very low dose, with early auditory responses observed in one patient," said Professor Catherine Birman, Senior Specialist at the Children's Hospital at Westmead, Australia. "We will continue the study in Cohort 2 to evaluate the efficacy of a higher dose. We selected children under 31 months of age who do not have cochlear implants because this period is a critical period for language development in the brain. This will allow us to assess the direct contribution of gene therapy to auditory abilities and maximize brain plasticity before the age of three to promote normal language learning."
Key Genes for Congenital Deafness: OTOF
Deafness caused by mutations in the OTOF gene, known as DFNB9 deafness, is an autosomal recessive form of congenital hearing loss. Patients are born with severe to profound hearing loss. The protein otoferlin, encoded by the OTOF gene, is involved in the fusion of calcium-dependent synaptic vesicles in inner hair cells and the release of neurotransmitters. When its function is impaired, sound signals are unable to reach the brain, leading to sensorineural hearing loss. Currently, there is no effective treatment for this disease. Cochlear implants, while the main treatment for severe DFNB9 patients, only partially restore hearing and have limitations such as distorted sound quality and difficulty perceiving sounds in noisy environments.
| Cat.No. | Product Name | Price |
|---|---|---|
| CSC-DC011158 | Panoply™ Human OTOF Knockdown Stable Cell Line | Inquiry |
| CSC-RO01392 | Mouse Otof Stable Cell Line - HEK293T | Inquiry |
| CSC-SC011158 | Panoply™ Human OTOF Over-expressing Stable Cell Line | Inquiry |
| AD11667Z | Human OTOF adenoviral particles | Inquiry |
| LV20763L | human OTOF (NM_194248) lentivirus particles | Inquiry |
| LV20764L | human OTOF (NM_194322) lentivirus particles | Inquiry |
| LV20765L | human OTOF (NM_194323) lentivirus particles | Inquiry |
Research has shown that inner hair cell development in patients with OTOF mutations is unaffected, with normal morphology. For such patients, gene therapy holds promise for achieving better outcomes than cochlear implants. Precise delivery of functional OTOF genes to the inner hair cells of the cochlea via adeno-associated virus (AAV) vectors is expected to repair synaptic transmission function and achieve hearing recovery close to physiological levels.
SENS-501: Dual AAV Gene Therapy
SENS-501 is a dual-vector AAV gene therapy that splits the OTOF gene into two parts and packages them separately into two AAV vectors, overcoming the capacity limitations of AAV vectors. Once inside cells, the two parts reassemble into the complete OTOF gene, directing the expression of otoferlin. Unlike the "replacement" interventions used in cochlear implants, SENS-501 aims to "restore" the inherent function of hair cells, theoretically resulting in more natural hearing restoration.
The project, initiated in 2019, has demonstrated promising potential in preclinical studies. Preclinical proof of concept demonstrated that the two halves of the otoferlin gene successfully reassembled in mice and durably restored cochlear receptor function.
Clinical Efficacy: Single Patient Demonstrates 145% Improvement in Hearing Ability
The data released today from the first cohort of an Audiogene clinical trial evaluating the safety, tolerability, and efficacy of intracochlear injections of SENS-501 in infants aged 6 to 31 months with congenital hearing loss due to an OTOF mutation were divided into two dose cohorts, each with three patients.
The primary objective of the first cohort (low-dose group) was to assess safety and feasibility. As of the data release, all enrolled patients demonstrated good tolerability, with no serious adverse events or side effects reported.
Of particular note, an 11-month-old patient in the first cohort showed early signs of hearing improvement three months after treatment: a positive auditory brainstem response (ABR) with a best frequency of 70dB; pure tone audiometry (PTA) demonstrated improved hearing within the speech frequency range; and a 16-point improvement in the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) score (a 145% relative improvement from baseline). Assessments have confirmed that the child has achieved expected auditory developmental milestones appropriate for their age.
Currently, enrollment in the secondary cohort (high-dose group) has been completed. Sensorion plans to announce further development plans once the secondary cohort data matures.