The US Food and Drug Administration (FDA) has granted accelerated approval for Otarmeni (lunsotogene parvec) for the treatment of patients with otoferlin (OTOF)-related hearing loss. The indication includes pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss associated with molecularly confirmed biallelic variants in the OTOF gene, preserved outer hair cell function, and no prior cochlear implant in the same ear.
In the clip below, Daniela Carvalho, MD, MMM, pediatric otolaryngologist at the University of California, San Diego, discusses clinical trial results and clinical experience that led to the approval.
OTOF-related hearing loss is a rare genetic auditory synaptopathy that results from defective synaptic transmission from normally functioning cochlear inner hair cells to the auditory nerve. The condition typically results in deafness at birth and current management involves cochlear implants.
Lunsotogene parvec, previously known as DB-OTO, is an adeno-associated virus vector-based gene therapy designed to deliver a working copy of the OTOF gene and restore durable, physiological hearing. It is administered via an infusion into the cochlea, similar to the procedure used for cochlear implantation.
The FDA approval is based on results from the CHORD clinical trial (NCT05788536), in which 20 participants, ages 10 months to 16 years, received a single dose of lunsotogene parvec, either unilaterally (n=10) or bilaterally (n=10). The CHORD study is an ongoing, multicenter, open-label, registrational clinical trial evaluating the safety and efficacy of lunsotogene parvec in patients with OTOF-related hearing loss.
Hearing improvements per pure tone audiometry assessments at a threshold of 70 or less dB HL at 24 weeks was observed in 80% of patients. One additional participant achieved this threshold by week 48. Additionally, 70% of patients demonstrated an auditory brainstem response at 90 or less decibels at 24 weeks. At 48 weeks, all prior responders maintained a response to therapy and 42% of participants achieved normal hearing that included whispers.
The most common adverse events in the safety population (n=24) associated with therapy included otitis media, vomiting, nausea, dizziness, procedural pain, gait disturbance, and nystagmus.
Lunsotogene parvec is the first gene therapy and second new molecular entity approved under the FDA’s National Priority Voucher program. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory portion of the CHORD clinical trial.
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To learn more about OTOF-related hearing loss and other rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/
