Lilly’s Investigational Gene Therapy Restores Hearing in First Treated Patient

Eli Lilly_iStock, jetcityimage

Pictured: Eli Lilly world headquarters in Indianapolis/iStock, jetcityimage

Eli Lilly on Tuesday announced that its investigational gene therapy AK-OTOF restored the hearing of a child within 30 days of administration in a Phase I/II trial.

The patient, an 11-year-old boy at the time of treatment, suffered from “profound hearing loss” since birth due to a genetic condition, according to Lilly’s announcement. Following treatment with AK-OTOF, however, the patient gradually recovered his hearing, reaching thresholds of 65 to 20 dB HL and eventually falling within the normal hearing range at some sound frequencies by day 30.

Lilly contends that AK-OTOF, as well as the surgical procedure to administer the gene therapy, was overall safe and well-tolerated with no serious adverse events.

“Gene therapy for hearing loss is something physicians and scientists around the world have been working toward for over 20 years,” John Germiller, attending surgeon and director of clinical research at the Children’s Hospital of Philadelphia, said in a statement.

“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,” Germiller said.

The 11-year-old patient is enrolled in Lilly’s AK-OTOF-101 study, a Phase I/II trial evaluating the safety, tolerability and bioactivity of AK-OTOF-101 at escalating doses. The study has an enrollment target of 14 patients, aged two to 17 years, across two locations in the U.S. and one in Taiwan. The Children’s Hospital of Philadelphia is one of the clinical trial sites for AK-OTOF-101.

Patients enrolled in AK-OTOF-101 suffer from a genetic form of hearing loss that arises from mutations in the otoferlin gene. Around 200,000 people worldwide suffer from otoferlin-mediated hearing loss, for which there are currently no approved pharmacologic answers.

Lilly’s AK-OTOF is a dual adeno-associated viral vector-delivered gene therapy that seeks to restore patients’ auditory abilities by delivering a functional copy of the otoferlin gene into the hair cells in the inner cochlea. AK-OTOF was initially developed by precision medicine specialist Akouos, which Lilly bought in October 2022 for $487 million.

AK-OTOF received the FDA’s Orphan Drug and Rare Pediatric Disease designations in April 2021.

Tuesday’s early-stage victory puts Lilly in direct competition with Regeneron, which is also developing an otoferlin gene therapy, dubbed DB-OTO.

In October 2023, Regeneron reported early findings from the first patient treated, an infant younger than two years of age. Through week six, the patient demonstrated improvements in auditory response, as measured by the auditory brainstem response, which is a validated physiologic measure of hearing sensitivity.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at or

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