Sensorion’s OTOF Hearing Loss Gene Therapy Cleared for Phase 1/2 Trial in France

Sensorion’s SENS-501 (also known as OTOF-GT), an investigational gene therapy intended for the treatment of otoferlin (OTOF) gene-mediated hearing loss, has received clearance of its clinical trial application (CTA) for the phase 1/2 Audiogene clinical trial (NCT identifier pending) in France.¹

Although Sensorion intends to initiate the trial in France first, the CTA covers France, Italy, and Germany under regulation EU 536/2014. The trial will recruit patients aged 6 to 31 months with the intent of treating them while auditory system plasticity is optimal. Initial participants in the trial be assigned to 1 of 2 cohorts in which they will receive either a lower dose or higher dose of the gene therapy. Later on, a dose expansion cohort will treat patients at the dose selected based on results from the dose escalation portion. In addition to evaluating the safety of the gene therapy itself, Audiogene will also evaluate the safety and efficacy of the surgical procedure for intracochlear injection and a device system developed by EVEON that is used for administration. Efficacy of SENS-501 will be assessed in the dose expansion portion via auditory brainstem response.

“SENS-501 represents a hope for numerous children born with deafness linked to a defect in the otoferlin gene and for whom no curative treatment exists today,” Natalie Loundon, MD, the director of the Center for Research in Pediatric Audiology, and a pediatric otolaryngologist and head and neck surgeon at Necker Enfants Malades, AP-HP, and the coordinating investigator of Audiogene, said in a statement.¹ “The administration of a single-injection therapy to very young children requires state-of-the-art hospital technical platform and health care givers team familiar with the handling of gene therapies. In keeping with our philosophy of supporting innovation wherever children's medical needs go unmet, we are delighted to be fully involved from the very beginning in this pioneering clinical trial.”

Sensorion noted that drug product for Audiogene has been successfully manufactured and that it expects to report results from the first patient treated in the trial within the second half of 2024. SENS-501 is being developed in collaboration with the Necker Enfants Malades Hospital, the Institut Pasteur, and the Fondation pour l’Audition, which together form a consortium referred to as Hospital Research-University (RHU) AUDINNOVE.

“This regulatory green light for the inclusion of patients in France in one of the world's first gene therapy trials in the field of hearing represents a major achievement for the teams at the Institut de l'Audition (Institut Pasteur center), and a crucial milestone in our strategic collaboration with Sensorion,“ Christine Petit, MD, PhD, a professor at the Institut Pasteur and professor emeritus at the Collège de France, added to the statement.¹ “The SENS-501 program, which aims to correct the deficiency of a gene responsible for congenital deafness in order to restore hearing, is based on very solid pioneering research elucidating the role of otoferlin and the pathogenic processes elicited by otoferlin defect. Its success will pave the way for other potential therapeutic innovations, based on gene therapy in many forms of deafness and for thousands of patients.”

Sensorion originally submitted the CTA for Audiogene in France, Italy, and Germany in July 2023.² During the same month, the company also submitted a CTA for Audiogene to the United Kingdom’s Medicines and Healthcare products Regulatory Agency.³ OTOF-GT functions by delivering OTOF via a dual adeno-associated virus vector for assembly in place.² It previously received orphan drug designation (ODD) and rare pediatric disease designation from the FDA in November 2022 and was also granted ODD by the European Medicines Agency in October 2022.^4-5

Despite the ultra-rare incidence of OTOF-related hearing loss, other companies are seeking to develop their own gene therapies for the same indication. These include Regeneron subsidiary Decibel Therapeutics’ DB-OTO and Eli Lilly 's AK-OTOF, both of which are currently being evaluated in clinical trials (NCT05788536 and NCT05821959, respectively).^6-7

REFERENCES
1. Sensorion announces approval to initiate lead gene therapy candidate SENS-501 (OTOF-GT) into a phase 1/2 clinical trial in some European countries. News release. Sensorion. January 19, 2024. Accessed January 26, 2024. https://s27.q4cdn.com/232015521/files/doc_news/Sensorion-Announces-Approval-to-Initiate-Lead-Gene-Therapy-Candidate-SENS-501-OTOF-GT-into-a-Phase-12-Clinical-Trial-in-some-European-PM76L.pdf
2. Sensorion submits clinical trial application for OTOF-GT, its lead gene therapy candidate, in Europe. News release. Sensorion. January 19, 2024. Accessed January 26, 2024. https://s27.q4cdn.com/232015521/files/doc_news/2023/07/19-07-2023_SENS_OTOF-CTA-Filing-in-Europe_ENG_FINAL.pdf
3. Sensorion submits clinical trial application for lead gene therapy candidate OTOF-GT in the UK. News release. Sensorion. July 10, 2023. Accessed January 26, 2024. https://s27.q4cdn.com/232015521/files/doc_news/2023/07/230627-SENS_Announces-CTA-Filing_MHRA_ENG.pdf
4. Sensorion announces US FDA grants Rare Pediatric Disease Designation to OTOF-GT for the treatment of otoferlin gene-mediated hearing loss. News release. Sensorion. November 7, 2022. Accessed July 11, 2023. https://s27.q4cdn.com/232015521/files/doc_news/2022/11/2022.11.07_Sensorion_-Rare-Pediatric-Disease-Designation_Eng.pdf
5. Sensorion receives Orphan Drug Designation for OTOF-GT for the treatment of otoferlin gene-mediated hearing loss from the US Food and Drug Administration. News release. Sensorion. November 30, 2022.Accessed July 11, 2023. https://s27.q4cdn.com/232015521/files/doc_news/2022/11/2022.11.30_-SENS_FDA-ODD-OTOF_ENG.pdf
6. Regeneron shares preliminary results showing gene therapy improves auditory responses in child with profound genetic hearing loss. News release. Regeneron. October 26, 2023. https://investor.regeneron.com/news-releases/news-release-details/regeneron-shares-preliminary-results-showing-gene-therapy
7. Lilly completes acquisition of Akouos expanding efforts to help people with genetic diseases. News release. Eli Lilly and Company. December 1, 2022. Accessed July 11, 2023. https://lilly.mediaroom.com/2022-12-01-Lilly-Completes-Acquisition-of-Akouos-Expanding-Efforts-to-Help-People-with-Genetic-Diseases