The sequencing dilemma in OTOF-related hearing loss
Industry Buzz
For suspected OTOF-related congenital deafness, genetic testing, cochlear implant evaluation, and, in highly suspicious cases, gene therapy referral should move in parallel—not sequentially. The child shouldn't lose weeks or months of auditory access while the system waits for one pathway to finish.
—Jeremy Woods, MD
A child with severe-to-profound congenital hearing loss linked to biallelic OTOF variants may now have more than one time-sensitive treatment pathway: established cochlear implantation or newly approved gene therapy.
That sequencing matters. The FDA-approved indication for lunsotogene parvec-cwha (Otarmeni) applies to pediatric and adult patients with severe-to-profound or profound sensorineural hearing loss linked to molecularly confirmed biallelic OTOF variants, preserved outer hair cell function, and no prior cochlear implant in the same ear. The therapy received accelerated FDA approval in April 2026.[]
Related: From devices to biology: What's new in congenital hearing loss care?The phrase “in the same ear” can create a management dilemma. If a child has already received a cochlear implant in one ear, that ear is no longer eligible for the approved OTOF gene therapy. This means doctors and families may need to decide whether to move ahead with cochlear implantation right away or first determine whether the child could qualify for gene therapy.
The old pathway
For decades, the goal was early auditory access. Newborn screening by 1 month, diagnosis by 3 months, and early intervention by 6 months remain the public health benchmarks. []
Cochlear implants also remain time-sensitive. The FDA Summary Basis for Otarmeni notes that cochlear implant devices are approved for children as young as 9 to 12 months and have been the established therapeutic option for OTOF-related hearing loss. []
The same FDA document also states the limitations. Cochlear implants bypass the dysfunctional synapse and stimulate the auditory nerve, but they do not modify the underlying condition. They do not restore normal hearing.[]
Related: Physicians share a 'wish list' for treating pediatric genetic hearing lossThe new pathway requires a pause
Clinicians now need enough time to answer three questions before implantation in a child with suspected OTOF-related deafness.
Is the hearing loss molecularly confirmed as biallelic OTOF?
Is outer hair cell function preserved?
Has the intended ear already received a cochlear implant?
But these determinations must happen in parallel without any delay. Jeremy Woods, MD, board-certified in pediatrics and medical genetics and genomics, as well as director of Valley Children’s Healthcare’s Prenatal Diagnostic Center and a physician in the hospital’s Medical Genetics and Metabolism Clinic, explains.
For suspected OTOF-related congenital deafness, genetic testing, cochlear implant evaluation, and, in highly suspicious cases, gene therapy referral should move in parallel—not sequentially. The child shouldn't lose weeks or months of auditory access while the system waits for one pathway to finish.
—Jeremy Woods, MD
How the gene therapy is administered
Otarmeni is a one-time intracochlear infusion. The FDA label says surgeons should confirm biallelic, likely pathogenic or pathogenic OTOF variants before treatment, and the product should be administered by a surgeon experienced in intracochlear surgery. []
Results from the pivotal DB-OTO-001 study supported FDA approval. In that trial, 16 of 20 evaluable patients met the primary endpoint at 24 weeks, and 5 of 12 patients with 48-week follow-up achieved hearing thresholds within the normal range, including the ability to hear whispers. []
The CHORD trial
CHORD is a global, open-label Phase 1/2 registration study testing Otarmeni for pediatric OTOF-linked deafness. It includes patients from infancy through age 17 and is recruiting at centers in the US, UK, Spain, Germany, and Japan.[]
A. Eliot Shearer, MD, PhD, a CHORD trial investigator at Boston Children’s Hospital, said, “The FDA approval of Otarmeni signals a new era in the treatment of genetic forms of hearing loss, where reinstating 24/7 natural hearing is now possible.” []
But multidisciplinary planning is still essential. Audiology, otology, genetics, speech-language pathology, pediatrics, and family counseling need to move in parallel.
Related: The diagnosis gap in pediatric hearing loss: Why one-size-fits-all protocols fall shortWhat families need to be told
So, how should physicians counsel families when cochlear implants offer established auditory access, but gene therapy eligibility may be affected by prior implantation in the treated ear?
According to Dr. Woods, “Families need to hear both truths: cochlear implants are established and time-sensitive while OTOF gene therapy is now a real disease-modifying option for eligible patients. Because current approval excludes a prior cochlear implant in the treated ear, ear selection and sequencing should be discussed before surgery.’’
Parents and caregivers should not be told that gene therapy is a guaranteed substitute for cochlear implantation. Otarmeni received accelerated approval based on improvement in hearing sensitivity at 24 weeks. Continued approval depends on confirming clinical benefit in the ongoing trial. []
They should also be counselled that the therapy is ear-specific. A prior implant in one ear affects candidacy for that same ear, but not necessarily the other ear.
What should centers prioritize?
According to Dr. Woods, “Centers should standardize a rapid pathway: diagnostic audiology review, expedited hearing-loss genetic testing, temporal bone imaging, genetics consultation, cochlear implant candidacy, gene therapy eligibility review, and a multidisciplinary ear-selection conference.’’
Related: A new gene therapy makes delayed OTOF diagnosis harder to defend