The US Food and Drug Administration has granted accelerated approval to lunsotogene parvec-cwha for the treatment of pediatric and adult patients with severe-to-profound sensorineural hearing loss associated with biallelic variants in the OTOF gene. The therapy represents an adeno-associated virus vector–based approach designed to restore hearing function by delivering a functional copy of the gene to cochlear hair cells.
The approval was supported by findings from the Phase 1/2 CHORD trial, which evaluated a single intracochlear administration in 20 patients aged 10 months to 16 years. Of these, 10 received unilateral treatment and 10 received bilateral treatment. At 24 weeks, 16 of 20 patients met the primary endpoint, defined as improvement in pure tone audiometry thresholds to 70 decibel hearing level or better, a level consistent with functional hearing that is not typically associated with cochlear implantation. One additional patient reached this threshold by week 48.
Objective measures of auditory function were also observed. Fourteen of 20 patients demonstrated auditory brainstem responses at 90 decibel hearing level or better at 24 weeks. Among patients with follow-up through 48 weeks, treatment responses were maintained, and 5 of 12 achieved hearing thresholds within the normal range, including whispers.
OTOF-related hearing loss is an ultra-rare condition affecting approximately 50 newborns annually in the US. The condition is characterized by lack of functional otoferlin protein, which is critical for communication between sensory cells of the inner ear and the auditory nerve. Standard management has relied on amplification devices, which improve sound detection but do not restore the full spectrum of sound.
The therapy is administered via intracochlear infusion under general anesthesia using a surgical approach similar to cochlear implantation. The therapy is indicated for patients with preserved outer hair cell function and is not recommended in those in whom access to the inner ear is not feasible. The therapy is also not indicated for patients who have previously received a cochlear implant in the ear to be treated.
Adverse events reported in the clinical program included otitis media, nausea, vomiting, dizziness, procedural pain, gait disturbance, and nystagmus. Surgical risks include meningitis, cerebrospinal fluid leak, and neurologic complications affecting the facial nerve. Continued approval is contingent on confirmation of clinical benefit in the confirmatory portion of the CHORD clinical trial.
Source: Regeneron Pharmaceuticals Inc.
