Sensorion Submits UK Clinical Trial Application for OTOF Hearing Loss Gene Therapy

Sensorion has submitted a clinical trial application (CTA) to the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for OTOF-GT, an investigational gene therapy intended for the treatment of otoferlin (OTOF) gene-mediated hearing loss.¹

Pending clearance of the CTA, the company intends to initiate the planned phase 1/2 Audiogene clinical trial, which will evaluate OTOF-GT in patients aged 31 months and younger. Sensorion stated that it has successfully manufactured the gene therapy product for use in the clinical trial. The company also noted that in the upcoming weeks it has plans for submission of a CTA in the European Union. OTOF-GT functions by delivering OTOF via a dual adeno-associated virus (AAV) vector for assembly in place.² It previously received orphan drug designation (ODD) and rare pediatric disease designation (RPDD) from the FDA in November 2022.^2,3 It was also granted ODD by the European Medicines Agency (EMA) in October 2022.

“This first gene therapy CTA filing is a major milestone for our OTOF-GT program and Sensorion’s broader gene therapy franchise,” Nawal Ouzren, the chief exectuive officer of Sensorion, said in a statement.¹ “This is the first of several planned CTA filings and we hope to commence patient recruitment soon, subject to the CTA approval. We look forward to continuing to work with clinicians, regulatory authorities and patient groups to address unmet and underserved medical needs in the intricate hearing space.”

OTOF-GT is not the only gene therapy currently in development for OTOF-mediated hearing loss. Decibel Therapeutics’ DB-OTO, an investigational AAV dual-vector-based gene therapy intended to treat otoferlin-related hearing loss being developed in collaboration with Regeneron Pharmaceuticals, received clearance of a CTA by the Spanish Agency of Medicines and Medical Devices in May 2023, clearance of a CTA by the UK’s MHRA in January 2023, and clearance of an investigational new drug application by the FDA in October 2022.^4-6 As of July 10, 2023, the phase 1/2 dose escalation clinical trial (CHORD; NCT05788536), is recruiting patients in the US, UK, and Spain. DB-OTO has been granted ODD by the EMA and ODD and RPDD by the FDA.

Meanwhile, Akouos's AK-OTOF, which is also an investigational dual AAV vector-based gene therapy intended for the treatment of OTOF-mediated hearing loss, received clearance of its IND application by the FDA in September 2022.⁷ Notably, on December 1, 2022, Akuous was acquired by Eli Lilly and Company.⁸ As of May 30, 2023, a phase 1/2 clinical trial (NCT05821959) evaluating AK-OTOF is recruiting patients aged 2 to 17 years with biallelic mutations in the otoferlin gene and profound bilateral sensorineural hearing loss at the Children's Hospital of Philadelphia. The FDA granted AK-OTOF ODD and RPDD in 2021.⁷

“There are currently no approved drugs for patients with mutations of the gene encoding for otoferlin,” Géraldine Honnet, the chief medical officer of Sensorion, added to the statement.¹ “Our goal is to transform the standard of care for OTOF newborns, by reducing dependence on cochlear implants, which would transform their quality of life. We believe that gene therapy has the potential to offer permanent solutions to patients with diseases caused by the OTOF mutation and other inner ear diseases and we are really excited to move OTOF-GT forward towards clinical development.”

REFERENCES
1. Sensorion submits clinical trial application for lead gene therapy candidate OTOF-GT in the UK. News release. Sensorion. July 10, 2023. Accessed July 11, 2023. https://s27.q4cdn.com/232015521/files/doc_news/2023/07/230627-SENS_Announces-CTA-Filing_MHRA_ENG.pdf
2. 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
3. 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
4. CTA authorization provides approval for the company to expand its planned CHORD™ phase 1/2 clinical trial of DB-OTO to patients in Spain aged two years and younger. News release. Decibel Therapeutics. May 12, 2023. Accessed July 11, 2023.https://ir.decibeltx.com/news-releases/news-release-details/decibel-therapeutics-announces-approval-clinical-trial-0
5. Decibel Therapeutics announces approval of clinical trial application by the U.K. Medicines and healthcare products regulatory agency for lead gene therapy candidate DB-OTO. News release. Decibel Therapeutics. January 24, 2023. Accessed July 11, 2023. https://ir.decibeltx.com/news-releases/news-release-details/decibel-therapeutics-announces-approval-clinical-trial
6. Decibel Therapeutics receives FDA clearance of IND application for DB-OTO, a gene therapy product candidate designed to provide hearing to individuals with otoferlin-related hearing loss. News release. Decibel Therapeutics. October 17, 2022. Accessed July 11, 2023.https://ir.decibeltx.com/news-releases/news-release-details/decibel-therapeutics-receives-fda-clearance-ind-application-db
7. Akouos receives FDA clearance of its IND application for AK-OTOF, a gene therapy intended for the treatment of OTOF-mediated hearing loss. News release. Akouos, Inc. September 13, 2022. Accessed July 11, 2023. https://investors.akouos.com/news-releases/news-release-details/akouos-receives-fda-clearance-its-ind-application-ak-otof-gene
8. 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