Regeneron's Hearing Loss Gene Therapy Shows Promise, FDA Filing Planned

Regeneron Pharmaceuticals is poised to make a significant leap in the treatment of genetic hearing loss, with plans to file a regulatory application for its gene therapy DB-OTO by the end of the year. This move follows compelling results from a Phase I/II clinical trial that demonstrated marked improvements in hearing for children with a rare form of genetic deafness.

Breakthrough Results in CHORD Study

The CHORD study, involving 12 patients with profound hearing loss due to mutations in the OTOF gene, has yielded promising outcomes. Eleven of the 12 participants experienced clinically meaningful improvements in hearing, with effects becoming apparent within weeks of treatment administration.

Key findings from the study include:

• Three children achieved normal hearing levels
• Eight patients showed either stable hearing or continued auditory improvements upon longer follow-up
• Nine participants reached hearing levels that would typically no longer require cochlear implants
• Six children could hear soft speech unassisted, while three could even detect whispers

The therapy's efficacy appeared to span various age groups, challenging previous assumptions that such treatments might only be effective when administered early in life.

Technical Aspects and Administration

DB-OTO is an adeno-associated virus-based gene therapy that delivers a functioning copy of the OTOF gene directly into the inner ear. The treatment is administered via an infusion in the ear, utilizing the same surgical approach as cochlear implants—a design choice aimed at ensuring surgeon familiarity and comfort with the delivery method.

Notably, the natural barrier separating the cochlea from the bloodstream appears to protect the therapy from neutralizing antibodies, which could otherwise interfere with its effectiveness. This characteristic may broaden the potential patient population for the treatment.

Safety Profile and Future Considerations

The therapy has demonstrated a generally favorable safety profile. While 67 adverse events were documented, most were minor and short-lived. Two serious adverse events were reported but resolved without causing additional health problems.

As with many gene therapies, questions remain about the long-term durability of DB-OTO's effects. Dr. Lawrence Lustig, a trial investigator and hearing specialist at Columbia University Medical Center, noted that while results are holding steady and even improving in long-term patients, the potential need for re-dosing in the future remains uncertain.

The development of DB-OTO represents a significant step forward in treating genetic hearing loss, potentially offering an alternative to cochlear implants for some patients. However, as Regeneron prepares for regulatory submission, it faces a competitive landscape with at least three other companies developing similar therapies, including Eli Lilly subsidiary Akouos.