EXCLUSIVE: A young child has become the first in Australia to receive pioneering gene therapy for deafness in a groundbreaking trial in Sydney, and two more were reported in September to be waiting to undergo treatment this year.
Medical Director of the cochlear implant program at NextSense (formerly Sydney Cochlear Implant Centre director), ENT surgeon Clinical Professor Catherine Birman OAM, performed the procedure in the third quarter of this year. She revealed details at the 36th World Congress of Audiology (WCA) in Paris on 20 September 2024.
The child has profound to severe hearing loss caused by mutations of the gene encoding for otoferlin (OTOF). OTOF deficiency is one of the most common forms of congenital deafness. The OTOF gene produces the protein otoferlin, needed to allow inner hair cells in the ear to communicate with the hearing nerve.
Professor Birman, Clinical Professor at Sydney University and Macquarie University, delivered the intra-cochlear injection of the therapy called SENS-501 and reported initial positive safety results for the patient.
A pioneer in the field of cochlear implants, particularly for children with complex medical conditions, paediatric and adult outcomes, Clinical Professor Birman is the Medical Director of the cochlear implant program at NextSense and a board member.
NextSense says Professor Birman is one of the most experienced cochlear implant surgeons in the world, having performed almost 2,000 cochlear implant procedures for children and adults from three months to well over 90 years.
“I am very excited to participate in this groundbreaking gene therapy trial that may have the potential to transform the lives of the babies carrying the OTOF gene mutation,” Prof Birman said. “The surgery was well tolerated by the patient and no safety signals were reported. From early observations, changes in the child’s behaviour and vocalisations were noted.
“I am grateful to the family of the first patient to receive the gene therapy for placing their trust in this innovative approach and potentially paving the way for the use of gene therapies in the aid of hearing loss. I am looking forward to following the progress of the first patient in the follow-up period and further recruitment of patients in (the) Audiogene (trial) assessing SENS-501 efficacy.”
The infant is possibly also the first in the world to receive this gene therapy from French biotechnology company Sensorion. At least seven other children from China, the UK and the US have received gene therapy from other companies for the same type of deafness with a conference hearing earlier this year that they had hearing restored, ‘marking a new era in deafness treatment.’
“Currently in the pre-clinical research phase, this gene therapy program represents significant hope for families affected by this rare form of genetic deafness,” Sensorion said, adding it had “the potential to dramatically improve the quality of life of patients with genetic deafness.”
Sensorion said SENS-501 (OTOF-GT) was developed to treat congenital deafness linked to mutations in the OTOF gene which plays a key role in the transmission of auditory signals between the hair cells of the inner ear and the auditory nerve.
“Its aim is to restore hearing by introducing a functional copy of the OTOF gene directly into hair cells via viral vector technology,” it added. “By replacing the defective gene, this therapy aims to restore the normal process of converting sound into electrical signals, enabling patients to regain their hearing ability.”
Prof Birman injected the therapy into the round window in the inner ear under general anaesthetic using a system developed in partnership with the company EVEON, so the injected dose could be measured precisely and the inner ear structures preserved.
Partner company, The Institut Pasteur, said a gene could only enter inner ear cells if transported by a viral vector capable of crossing the cell membrane. The adeno-associated virus (AAV) delivered the gene but as the gene was so big, it was divided into two DNA fragments each transported by an AAV, which were then assembled inside the inner ear cells.
Sensorion said its phase 1/2 clinical trial called Audiogene aimed to evaluate safety, tolerability and efficacy of the treatment in infants aged six to 31 months at the time of injection.
It said initial safety data indicated no serious or adverse events were detected after administration. “The medical condition of the child (upper respiratory infection unrelated to SENS-501 injection) at the time of efficacy assessment (ABR month 1) did not allow to get reliable hearing sensitivity,” Sensorion said.
“By targetting the early years of life, when auditory system plasticity is optimal, the therapy seeks to maximise the chances for children with pre-lingual hearing loss to acquire normal speech and language.”
Two other patients
Sensorion said two additional patients had been screened and anticipated completion of the first cohort of three patients and publication of initial efficacy data by the end of 2024. Recruitment completion of the second cohort of three patients is planned by June 2025.
The study involves two cohorts of two doses, followed by an expansion cohort at the selected dose. While safety will be the primary endpoint for the dose escalation cohort, auditory brainstem response will be the primary efficacy endpoint of the dose expansion cohort.
Audiogene will also assess clinical safety, performance and usability of the administration device system.
Sensorion CEO, Ms Nawal Ouzren, said: “Sensorion is making tremendous progress across its hearing care franchise of innovative therapies for the restoration, prevention and treatment of hearing loss disorders. Notably, we have made significant advances in our gene therapy clinical trial, Audiogene, for the restoration of hearing in very young patients born with severe to profound hearing loss caused by mutations in the gene encoding for otoferlin.
“This program received regulatory approval in January 2024, and we are today confident that we will have treated the first cohort of patients by year end 2024, with one patient already injected and two additional patients already screened. I am very thankful to the parents of these patients for their trust and to the study investigators participating in this study for their dedication.”
The therapy was developed under the RHU AUDINNOVE consortium comprising Sensorion, the Necker Enfants Malades Hospital, the Institut Pasteur, and the Fondation pour l’Audition.
