iStock,
unomat
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-pro
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.
Gene therapy
Regeneron Readies FDA Run for Hearing Loss Gene Therapy That Could ‘Transform Patients’ Lives’
Regeneron is aiming to regulatory application for DB-OTO by the end of the year.
October 13, 2025
·
2 min read
·
Tristan Manalac
Read more
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 pro 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.
Gene therapy
Sarepta’s Woes Put the Stalwart AAV Under a Harsh Light
In the wake of multiple patient deaths from liver injuries related to Sarepta Therapeutics’ AAV gene therapy platform, some in the sector are looking for ways to improve the current technology, while others are eager to move on.
August 11, 2025
·
7 min read
·
Dan Samorodnitsky
Read more
“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.”
Gene editing
Lilly Leans Into Hearing Loss in $1.12B+ Gene Editing Pact With Seamless
The deal will help bolster Eli Lilly’s growing hearing loss portfolio, which is anchored by the gene therapy AK-OTOF.
January 28, 2026
·
2 min read
·
Tristan Manalac
Read more
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.”
.responsive-container {
display: flex;
flex-wrap: wrap;
border: 1px solid #ededed;
font-family: Helvetica, Arial, Sans-Serif;
padding: 20px 20px 10px 20px;
}
.column-left {
flex: 1;
max-width: 45%;
padding: 20px 20px 10px 20px;
}
.column-right {
flex: 2;
padding: 20px 20px 10px 20px;
}
@media (max-width: 768px) {
.column-left,
.column-right {
max-width: 100%;
flex: 100%;
padding: 10px 0;
}
}
Subscribe to ClinicaSpace!
Clinical trial results, research news, the latest in cancer, cell and gene therapy
hbspt.forms.create({
region: "na1",
portalId: "4413123",
formId: "674f4dc0-7371-4190-86cc-e1afd00b08ea",
onFormSubmitted: function($form, data) {
window.dataLayer = window.dataLayer || [];
window.dataLayer.push({
'event': 'GTMevent',
'event_name': 'newsletter_sign_up'
});
}
});
