The FDA has approved Regeneron’s Otarmeni (lunsotogene parvec-cwha, formerly known as DB-OTO) as the first-ever gene therapy for the treatment of OTOF-related genetic hearing loss.
Cleared under the FDA Commissioners’ National Priority Voucher (CNPV) program, the one-time treatment offers a potential functional cure for patients with inherited forms of deafness, conditions that have historically lacked disease-modifying therapies.
OTOF-related hearing loss is an ultra-rare condition that affects around 50 newborns every year in the US. As a recessive genetic condition, those who develop the disease inherit two faulty copies of the otoferlin gene, one from each parent.
Though all structures within the ear are intact, variants in the OTOF gene cause a lack of a functional otoferlin protein, which is critical for transmitting sound signals from the sensory cells of the inner ear to the auditory nerve in the brain.
Historically, genetic OTOF-related hearing loss was considered permanent and managed with lifelong use of devices. While these devices can amplify sound to improve hearing for individuals with a range of hearing loss, they do not currently restore the full spectrum of sound.
Otarmeni is approved for pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss (any frequency >90 dB HL) associated with biallelic variants in the OTOF gene. It is indicated for patients with preserved outer hair cell function and no prior cochlear implant in the same ear.
By delivering a functional copy of the gene directly into inner ear cells via an adeno-associated viral (AAV) vector, the therapy aims to restore the production of otoferlin. Early clinical trials demonstrated meaningful improvements in auditory function, with several pediatric patients gaining the ability to detect sound and, in some cases, develop speech perception.
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Regeneron says Otarmeni is the first FDA-approved example of a gene therapy to restore a neurosensory function to normal levels.
“Otarmeni is a huge scientific leap and is representative of Regeneron’s approaches to continually push the boundaries of science to benefit humanity,” said George D. Yancopoulos, MD, PhD, Board co-Chair, President and Chief Scientific Officer of Regeneron, in a company statement. “This unprecedented breakthrough in gene therapy has already proven to be life-changing for many of the children in our clinical trial and their families. We are honored to be in the position to be the first company to ever offer such a gene therapy advance for free to those in the US and serves to highlight our belief that the biopharmaceutical industry can be a genuine force for good in the world.”
The FDA approval was supported by results from the pivotal CHORD trial, in which 20 participants (aged 10 months to 16 years) received a single dose of Otarmeni via intracochlear infusion, with half receiving the dose unilaterally in one ear and the other half bilaterally in both ears.
Among the participants, 80% (16 of 20) met the trial’s primary endpoint, experiencing hearing improvements per pure tone audiometry assessments at a threshold of ≤70 dB HL at 24 weeks. One additional participant achieved this threshold by Week 48. This threshold corresponds to a clinical standard that enables natural hearing and typically does not require cochlear implantation.
Also at 24 weeks, 70% (14 of 20) had an auditory brainstem response (ABR) at ≤90 decibels, achieving the trial’s key secondary endpoint. Regeneron explains that ABR is an objective confirmation of hearing function, as measured by recording electrical brainstem signals in response to sound.
For those followed to the 48-Week mark, all prior responders maintained a response to therapy, while 42% of all participants (five of 12) achieved normal hearing that included whispers (≤25 dB HL).
After the publication of the trial data in the New England Journal of Medicine, the FDA issued the CNPV to expedite review. The therapy was approved just 61 days after BLA submission, becoming the sixth product cleared under the CNPV pilot, and the first gene therapy to do so. The decision also ranks among the fastest BLA approvals in modern FDA history.
The controversial CNPV program is an initiative designed to accelerate review timelines for therapies addressing rare and serious conditions. The program has drawn criticism for potentially prioritizing speed over thorough review, with some experts concerned it could strain FDA resources and increase the risk of approving therapies with more limited clinical data.
Regeneron said it will provide Otarmeni at no cost to clinically eligible individuals in the US. But out-of-pocket costs related to the administration of this therapy may vary and are not determined by Regeneron, the company explained. As such, patients are encouraged to consult their healthcare provider and/or insurance provider for specific coverage and cost information.
“Connection and communication are at the heart of how we experience the world — whether that happens through listening and spoken language, sign language, the use of technology or a combination of approaches,” said Janet DesGeorges, Executive Director of Hands & Voices, in the Regeneron press release.
“Families deserve access to balanced information and a range of options when navigating genetic hearing loss. As new treatments and innovations emerge, families can assess available options and choose the approach best suited to their unique circumstances,” added DesGeorges.
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