A new gene therapy makes delayed OTOF diagnosis harder to defend
Industry Buzz
Genetic confirmation should be treated as urgent. The clinical risk is not simply delayed diagnosis; it is delayed auditory input during a critical window for speech and language development.
—Jeremy Woods, MD
For decades, the pathway for addressing pediatric hearing loss was fairly straightforward. A baby fails newborn hearing screening, diagnostic testing confirms severe hearing loss, and the family is referred for hearing aids, early intervention, and often cochlear implant evaluation.
But now there is a new variable: Genetics.
In April 2026, lunsotogene parvec-cwha (Otarmeni) was approved by the FDA as first-line gene therapy for hearing loss caused by mutations in the OTOF gene. The treatment was approved only for patients with molecularly confirmed biallelic OTOF variants, preserved outer hair cell function, and no prior cochlear implant in the ear being treated. []
The challenge for clinicians is forging the best management plan for children with profound hearing loss. If OTOF-related disease is suspected, teams now need genetic answers early enough to determine whether gene therapy is an option before implantation plans move forward.
When to suspect OTOF
OTOF-related hearing loss is an auditory synaptopathy. The cochlea’s outer hair cells often function, but transmission from inner hair cells to the auditory nerve fails.
GeneReviews describes the classic pattern: congenital or prelingual bilateral hearing loss that is typically severe-to-profound, and associated with normal otoacoustic emissions (OAE) but abnormal auditory brainstem response.[]
This creates a known screening problem. Newborn hearing screening based only on OAE testing will miss many typical OTOF cases, because OAE testing mainly reflects outer hair cell activity. AABR-based screening is more likely to detect the disorder. []
Related: Physicians share a 'wish list' for treating pediatric genetic hearing lossClinicians should think about OTOF when a child has severe-to-profound congenital SNHL, poor speech discrimination, preserved OAE or other evidence of outer hair cell function, abnormal ABR, normal imaging, nonsyndromic presentation, or family history compatible with autosomal recessive disease.
Jeremy Woods, MD, board-certified in pediatrics and medical genetics and genomics, and director of Valley Children’s Healthcare’s Prenatal Diagnostic Center and a physician in the hospital’s Medical Genetics and Metabolism Clinic, says, “OTOF should be high on the list when a newborn has severe-to-profound hearing loss.’’
A 2025 AAO-HNS Bulletin report states that all children with congenital SNHL should undergo genetic testing. The hearing loss gene panel has a diagnostic yield of 43% overall, with a range of 20% to 60% depending on phenotype. []
What physicians are saying
Oliver Haag, MD, a pediatric otolaryngologist in Barcelona, and an investigator in the Akouos AK-OTOF-NHS-002 Natural History Study, said children with OTOF-mediated hearing loss are often born with profound hearing loss, “yet only a small fraction have undergone genetic testing to receive a definitive diagnosis.” []
Dr. Woods discusses the need for timely diagnosis, stating, “Genetic confirmation should be treated as urgent. The clinical risk is not simply delayed diagnosis; it is delayed auditory input during a critical window for speech and language development."
John Germiller, MD, PhD, of Children’s Hospital of Philadelphia, and a principal investigator for the AK-OTOF-101 clinical trial, commented on the early AK-OTOF trial results, saying, “Gene therapy for hearing loss is something physicians and scientists around the world have been working toward for over 20 years.” He added, “These initial results show that it may restore hearing better than many thought possible.” []