▎WuXiEdited by Kant Content Team

Regeneron Pharmaceuticals today announced preliminary positive results from the Phase 1/2 CHORD trial.A patient with hereditary deafness who received the investigational gene therapy DB-OTO at 11 months old recovered to normal hearing levels within 24 weeks, while another patient who received the therapy at age 4 also showed preliminary improvements in hearing 6 weeks after treatment.Both children were hospitalized due toOTOFChildren with severe hereditary deafness caused by genetic mutations were treated at 11 months old, making them one of the earliest patients globally to receive gene therapy for hereditary deafness. The CHORD trial is currently recruiting infant and pediatric patients, with relevant data presented at this year's American Society of Gene & Cell Therapy (ASGCT) annual meeting.

In the trial, both patients received a single intracochlear injection of DB-OTO in one ear, with the procedure performed using the same method as cochlear implantation, suitable for infant and pediatric patients. Hearing improvement was assessed through pure-tone audiometry (PTA) and auditory brainstem response (ABR). PTA is considered by audiologists to be the gold standard for hearing measurement, evaluating behavioral responses (such as head-turning) to sounds emitted at varying intensity levels (decibels). ABR objectively confirms the subject's auditory function by measuring the brainstem’s electrical responses to sounds at different decibel levels.

At baseline measurement, two participants had maximum volume (≥100Decibel) with no behavioral (PTA) or electrophysiological (ABR) response.Both patients showed hearing responses at the first efficacy assessment in Week 4 after receiving DB-OTO treatment.The main results of the data published this time are as follows:

• The first subject in the trial was only 16 months old at the 24-week assessment of the trial.The patient's hearing returned to normal levels in the main speech frequency range, with an average hearing response improvement of 84% from baseline.Decibel, one of which frequency measurement reaches the PTA hearing level of 10Decibel。All showed an 80-point improvement in average hearing response to test frequencies compared to baseline.Decibel. The patient'sABR reaction was positive,Among them, the patients' best response to different frequencies reached 45.Decibel。

• The second subject was only 4 years old at the 6-week assessment of the trial, with results consistent with the first subject, including preliminary improvement in hearing and the ability to respond to loud sounds.The average hearing in the main speech frequency range improved by 19 compared to the baseline.Decibel, the measurement of one of the frequency responses reaches 80% of the PTA hearing level.Decibel。CorrectThe average hearing response at all test frequencies improved by 16 compared to baseline.Decibel. In addition, the subject's ABR response was positive, with the patient's best response to different frequencies reaching 75.Decibel。

• In addition, the surgical procedure (including therapy delivery and post-operative manipulations) and the DB-OTO therapy itself were both well-tolerated, with no related adverse events or serious adverse events observed post-treatment.

DB-OTO is an investigational cell-selective adeno-associated virus (AAV) gene therapy designed to deliver via an AAV vectorOTOFA healthy copy of the gene is delivered to the cochlear hair cells, forOTOFPatients with congenital profound hearing loss caused by genetic mutations are provided with lasting physiological hearing.Previously, DB-OTO has received orphan drug designation, rare pediatric disease designation, and fast track designation from the FDA.

References:

[1] LATEST DB-OTO RESULTS SHOW DRAMATICALLY IMPROVED HEARING TO NORMAL LEVELS IN A CHILD WITH PROFOUND GENETIC DEAFNESS WITHIN 24 WEEKS AND INITIAL HEARING IMPROVEMENTS IN A SECOND CHILD AT 6 WEEKS. Retrieved May 8, 2024 from https://investor.regeneron.com/news-releases/news-release-details/latest-db-oto-results-show-dramatically-improved-hearing-normal

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