Eli Lilly and Regeneron are leading the push to treat congenital deafness with gene therapies, seeking a piece of a potential billion-dollar market and banking on local delivery and the small amount of drug required to overcome key safety concerns.
The last year has been challenging for the gene therapy space.
A series of deaths—headlined by the high-profile case of Sarepta’s Elevidys—has cast doubts about safety, while rejections, delays and study holds have dampened the economic case for developing gene therapies. But there is one disease area where the modality is thriving: hearing loss.
“The stage is set to make an impact in the auditory area with gene therapies over the next decade,” Jonathon Whitton, vice president and global program head for Genetic Medicines at Regeneron, told BioSpace in an email.
Regeneron is competing with Eli Lilly to bring the first gene therapy for deafness to the market.
The company’s DB-OTO, which aims to restore the expression of otoferlin—a protein encoded by the OTOF gene that is critical to the hearing process—in patients with congenital deafness. DB-OTO—elicited “clinically meaningful” improvements in hearing within weeks of dosing in a Phase 1/2 trial in October 2025.
Meanwhile, Lilly’s AK-OTOF, a dual adeno-associated viral vector-delivered gene therapy, restored the hearing of a child in January 2024.
“Millions of individuals worldwide have disabling hearing loss because one of their genes generates an incorrect or incomplete version of a protein [otoferlin] the ear requires for hearing,” a Lilly spokesperson told BioSpace in an email. AK-OTOF, they continued, delivers a functional copy of the otoferlin gene to elicit “durable expression of functional otoferlin protein to the inner hair cells of the cochlea.”
There is currently no treatment for the approximately 1 in 500 infants in the U.S. who are born with some form of deafness each year, Whitton said. Genetic anomalies account for more than half of these cases, he continued, which can be diagnosed with a saliva sample and genetic testing.
This means that the potential market “is huge,” Zheng-Yi Chen, associate scientist at the Eaton-Peabody Laboratories at Massachusetts Eye and Ear, told BioSpace in an email, “which is attractive for the pharma/biotech industry.”
Indeed, the global market for hereditary deafness is expected to exceed $1 billion by 2033, up from $610 million this year, according to a recent report by Coherent Market Insights.
Lilly and Regeneron are both well-positioned to take advantage. AK-OTOF’s Phase 1/2 study is expected to wrap up in October 2028, while a regulatory package for DB-OTO was filed late last year, with a decision expected in the first half of this year.
Success in the hearing loss space could have positive implications across gene therapy, experts agree.
A Safety Audible
In theory, “applying gene therapy to treat hearing loss or deafness makes sense” for several reasons, not least of which is the monogenic nature of the disease, according to Graig Suvannavejh, managing director of Equity Research, Biopharmaceuticals and Biotechnology at Mizuho Securities.
This is true for congenital forms of hearing loss, at least. “It’s important to keep in mind that for the other 50% of patients with hearing loss, their condition came from acquired causes,” Suvannavejh clarified in an email. “So a gene therapy won’t help them.”
Aside from the relatively simple genetics of the disease, however, the cleaner safety profile of ear-targeted gene therapies is another key advantage, Suvannavejh said.
Chen agreed, explaining that the heaviest toxicity concerns with gene therapy stem from adeno-associated virus (AAV) vectors, which are used to package the genetic payloads and protect them from temperature and chemical assaults when inside the body.
Last summer’s Elevidys saga shone a harsh light on the use of AAVs, highlighting their propensity to accumulate in the liver and damage the organ. AAVs are also highly immunogenic, meaning they trigger a response from the immune system, which can further damage the liver or even spiral into a more systemic reaction like a cytokine storm.
“In most cases where death has been reported, AAV was administered systematically in large quantities, which resulted in toxicity,” Chen said. “For diseases where local delivery is feasible, such as the eye and the inner ear, the risk is greatly reduced.”
Hearing loss is a perfect test case for this, Chen and Suvannavejh agreed. Not only is the delivery of gene therapies for deafness very localized, but it can also be done via well-established surgery techniques, further minimizing injuries that can come from risky procedures, Suvannavejh said.
In addition, as deafness is not a fatal condition, patients enrolled in gene therapy trials for hearing loss are “relatively healthy,” the Mizuho analyst continued, meaning they are easier to treat and suffer from fewer comorbidities and complications.
Listening to the Market
Another key allure of the hearing loss space is its attractive market proposition.
In its report, Coherent Market Insights recognized that precision therapies have the “potential to revolutionize treatment” for hereditary deafness. This will drive demand for targeted treatments, the market intelligence firm said, much like the ones Lilly and Regeneron are developing.
Both companies have recognized the potential returns and have invested accordingly. Lilly, for instance, bought into the field in October 2022, when it acquired Akouos in a $487 million cash transaction, gaining access to AK-OTOF. The pharma has continued to pump money into its hearing loss precision portfolio, betting up to $1.3 billion in May 2025 for access to Rznomics’ RNA editors. Earlier this year, Lilly again put more than $1 billion on the line to advance site-specific recombinases with Seamless Therapeutics.
Regeneron gained ownership of DB-OTO when it swallowed partner Decibel Therapeutics for $109 million in August 2023.
Gene therapies for hearing loss are less costly to bring to market than those for other indications, according to Suvannavejh. “The amount of drug needed for a hearing loss gene therapy is very small,” he explained, “So the cost of goods is low—probably much lower relative to other gene therapies that need to be delivered systemically.”
Regeneron’s Whitton agreed, noting that the requirement of just a small amount of the therapeutic material makes things a bit easier for drugmakers. “Drug development is a tough industry,” he said. The ability to keep doses low, along with local delivery, “helps to address many of the challenges that systemic gene therapies have faced.”
An Ear to the Future
More broadly, the current hearing loss push could have far-reaching implications for the gene therapy space as whole, Whitton said.
“There is something powerful about the broader momentum that progress creates,” he said. “A meaningful result in one area, even a rare one, can show the field what is possible and gives others the confidence to take similar chances.”
One example of this is the creation of dual-AAV gene therapies, Chen said, which were “first applied successfully to genetic hearing loss.” Because this platform uses two vectors, it is able to introduce large genes that wouldn’t have otherwise fit into a single AAV package, according to a 2019 study published in PNAS, which used this technique to deliver two halves of the otoferlin gene into mice. The genetic payload was successfully reconnected in the animals’ inner ear, reversing deafness.
Another mouse study published in Clinical and Translational Medicine in January validated the dual-AAV approach in hearing loss, showing that the platform can deliver the entire length of the STRC gene—also commonly mutated in congenital forms of deafness—into the animals, likewise restoring hearing.
While the technology is still in its infancy, the dual-AAV approach has “opened a new avenue for efficacious treatments,” Chen said.
Italian biotech AAVantgarde is trying to bring this platform into the clinic. Its lead program targets Usher syndrome, a rare genetic disorder that causes partial or total hearing loss and progressive blindness. The company completed enrollment in a Phase 1/2 study in this indication in January.
Aside from dual AAVs, Chen pointed to other novel modalities, such as antisense oligonucleotides, gene editors and RNA therapies, which he believes will also be leveraged for hearing loss in the coming years.
Suvannavejh is similarly excited about the field’s future, though more cautiously so.
“I am not particularly sure about potential read-throughs to gene therapies for other conditions,” he said, again referencing the localized delivery of hearing loss therapies—a key distinction he insisted makes them “rather unique” from systemic genetic medicines.
“That said,” Suvannavejh continued, “I think any positive advancement in gene therapy for hearing loss . . . will likely only stimulate more interest by both industry and the investment community in gene therapies for hearing loss, as well as in the gene therapy space overall.”
