Science1 publisher2 min readPublished
Regeneron's Otarmeni becomes the first US-approved gene therapy for hearing loss
Regeneron's Otarmeni won FDA approval in April as the first gene therapy for hearing loss, with 42 percent of 24 treated children since regaining hearing. The deafness it treats leaves the rest of the ear intact. How far the approach can reach beyond this one gene is still unknown.
The Scientist · Science desk
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What happened
- In the CHORD trial, half the participants received one surgical infusion into a single ear and the other half received a one-time dose in both ears.
- Before Otarmeni, the last major advance for this deafness was the cochlear implant, which the FDA approved for children 12 months and older in 2000.
- Akouos, owned by Eli Lilly, France's Sensorion and China's Shanghai Refreshgene Therapeutics have each started early-phase trials of their own OTOF gene therapies.
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Why it matters
- constraint Congenital hearing loss affects 1 in 500 babies and OTOF causes 1 to 8 percent of it. That puts the therapy's reach at somewhere between one birth in 6,250 and one in 50,000.
- decision Confirming DFNB9 takes a genetic test after the hearing test, so whether a deaf infant is offered the therapy now depends on someone ordering that test.
- precedent With the FDA's approval of a gene therapy delivered by surgery into the inner ear, the OTOF programmes still in early trials will be judged against a product already on the market.
Counted in children, the CHORD figures are small. Forty-two percent of 24 participants is about 10 [1], and around 80 percent is about 19 [2]. That leaves roughly nine whose hearing improved within 24 weeks but who have not reached what Nature reports as regained hearing [3]. Each dosing group held 12 [4]. Nature's account does not define the hearing level that counts as regained or split the results by group, and the trial is still running [3].
I would still read a gain in about four of five children born with this deafness as a real effect of the treatment [5]. The figures a family would weigh are still to come: how many end up with regained hearing after longer follow-up, and whether treating both ears adds anything over treating one.
OTOF went first for a biological reason. The gene encodes a protein needed to carry sound signals from the inner ear to the auditory nerve [7]. Otarmeni is built to deliver a working copy of it to the ear's hair cells [8]. According to Nature, Dylan Chan, a paediatric otolaryngologist at the University of California, San Francisco, describes OTOF as relatively low-hanging fruit for treatment [18]. "This is a unique situation in hearing loss, where everything in the ear is formed normally, everything functions normally, except there's one missing protein that makes the synaptic transmission not function," Chan said [11]. "It's a huge breakthrough because we've never been able to treat the inner ear before," he said [12].
OTOF is one of more than 150 genes tied to non-syndromic genetic hearing loss, the kind that occurs outside any broader syndrome [10]. The approval does not show whether gene replacement helps in ears that are not, in Chan's words, "formed normally" [11].
Confirming the diagnosis used to fall on families. In the US in the 1990s, genetic testing was not covered by health insurance, and many families paid for it themselves, according to Daniel Lee, a neurotologist at Harvard Medical School [16].
Nature also notes that many Deaf people do not consider the condition a disability that requires a cure, and that individuals often identify as part of Deaf culture [17].
What to watch
- A full CHORD report that defines regained hearing and separates results for one-ear and two-ear dosing.
- Longer follow-up from the ongoing CHORD trial, showing whether the share with regained hearing rises above 42 percent or the gains fade.
- First results from the early-phase OTOF trials run by Akouos, Sensorion and Shanghai Refreshgene.