Eli Lilly said its experimental gene therapy restored hearing in a boy born with profound hearing loss. The results for this experimental treatment come three months after Regeneron Pharmaceuticals reported early but encouraging data for its hearing loss gene therapy.

By FRANK VINLUAN
Gene therapy made its first breakthroughs slowing vision loss from inherited eye disorders. Eli Lilly is making the ear this therapeutic modality’s next proving ground, and the pharmaceutical giant now has some encouraging early clinical trial results showing it can work.

An 11-year-old boy with profound hearing loss experienced restored hearing within 30 days of receiving the gene therapy, AK-OTOF, Lilly announced Tuesday. These are results for just one patient—the first in a clinical trial that could enroll up to 150 participants. But this early result is a promising sign for the therapy, which Lilly gained in 2022 through the $487 million acquisition of its developer, Akouos.

Hearing loss has many causes. AK-OTOF was developed specifically for hearing loss due to mutations to OTOF, a gene that encodes otoferlin, a protein key to the activation of auditory neurons. Dosed with a medical device designed for intracochlear administration, the Lilly gene therapy delivers a functioning version of this gene to inner hair cells of the ear. Similar to gene therapies developed for the eye, AK-OTOF employs an adeno-associated virus (AAV) to carry the genetic payload to cells. But the larger size of the OTOF gene requires a dual AAV, each part carrying a fragment of the gene. The gene therapy is intended to restore expression of normal, functional otoferlin protein.

Lilly’s Akouos subsidiary is evaluating AK-OTOF in a Phase 1/2 clinical trial. Besides assessing the safety and tolerability of the therapy, the study’s goals include measuring auditory brainstem response. According to Lilly, the boy who received the gene therapy had hearing tested across all frequencies and posted results “within the normal hearing range at some frequencies at the Day 30 visit.” The therapy was administered by John Germiller, attending surgeon and director of clinical research in the Division of Otolaryngology at Children’s Hospital of Philadelphia.

“Gene therapy for hearing loss is something physicians and scientists around the world have been working toward for over 20 years,” Germiller, a principal investigator of the clinical trial, said in a prepared statement. “These initial results show that it may restore hearing better than many thought possible.”

Lilly did not elaborate about the hearing results, but said the surgical administration procedure and the therapy were well tolerated with no serious adverse effects. More information is coming soon. Lilly plans to present details from the clinical trial on Feb. 3 during the 2024 mid-winter meeting of the Association for Research in Otolaryngology in Anaheim, California.

Lilly’s closest hearing loss gene therapy competitor is probably Regeneron Pharmaceuticals, which last year acquired its gene therapy partner Decibel Therapeutics in a deal that could reach up to $213 million if milestones are met. Decibel’s DB-OTO program, a gene therapy for hearing loss caused by otoferlin gene mutations, is currently in Phase 1/2 testing. Last October, on the heels of closing the Decibel acquisition, Regeneron said the first patient in the study showed improvements in auditory responses through week six compared to baseline. No serious adverse events were reported. The clinical trial is continuing to enroll patients.

Though hearing loss has been a tough road for drug developers, at least one pharmaceutical company can claim success. In 2022, Fennec Pharmaceuticals won FDA approval for Pedmark, a drug developed to prevent the hearing loss complication that is common in pediatric cancer patients treated with chemotherapy.

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