Eli Lilly Gene Therapy Restores Hearing Within 30 Days

On January 23, 2024, Eli Lilly and the Children’s Hospital of Philadelphia announced the success of an experimental gene therapy for patients with genetic hearing loss. According to the press releases, Lilly’s early-stage gene therapy helped restore hearing in an 11-year-old with genetic hearing loss at the Children’s Hospital of Philadelphia’s Division of Otolaryngology within 30 days of treatment.

The patient was recruited as part of the phase 1/2 AK-OTF-101 clinical trial. The study is evaluating the efficacy of AK-OTOF gene therapy, which is a dual adeno-associated viral (AAV) vector-based treatment that alters the patient’s genes and prompts it to correctly express the otoferlin protein in the inner hair cells of the cochlea.

“AK-OTOF utilizes AAVAnc80, a capsid with high transduction efficiency for inner hair cells, together with a strong ubiquitous promoter to achieve expression of otoferlin, observed only in the target inner hair cells, at levels that have the potential to restore high acuity physiologic hearing,” explained the press release.

According to the announcement from the Children’s Hospital of Philadelphia, the 11-year-old patient was the first one to be enrolled in the AK-OTF-101 clinical trial. The patient was born with hearing loss in both ears associated with an OTOF gene mutation.

On October 4, 2023, this patient received the gene therapy through a surgical procedure that allowed doctors to deliver a single small dose of the gene therapy into the inner ear.

Despite starting the study completely deaf in both ears, the patient’s hearing was restored within 30 days across multiple frequencies with thresholds from 65 to 20 dB HL. Beyond that, the patient’s experience provided evidence that the gene therapy and procedure required to deliver it were well tolerated and safe, as the patient did not experience any adverse events.

"Gene therapy for hearing loss is something that we physicians and scientists in the world of hearing loss have been working toward for over 20 years, and it is finally here," said John A. Germiller, MD, PhD, an attending surgeon and Director of Clinical Research in the Division of Otolaryngology at CHOP, and Associate Professor at Perelman School of Medicine at the University of Pennsylvania, in the release. "While the gene therapy we performed in our patient was to correct an abnormality in one, very rare gene, these studies may open the door for future use for some of the over 150 other genes that cause childhood hearing loss.”

Eli Lilly will be presenting the clinical trial results and revealing data on a second patient at the 2024 Association for Research in Otolaryngology MidWinter Meeting.

Hearing loss can significantly impact quality of life. While this study is focused on hereditary hearing loss, multiple studies have found a correlation between progressive hearing loss and dementia or other neurological conditions. Successes in treating genetic hearing loss may have implications in treating other kinds of hearing loss.

Although more data is needed to confirm the results of this study, gene therapies for restoring hearing are a large area of focus.