FDA clears first genetic hearing loss gene therapy

Regeneron has become the first company to get US approval for a gene therapy for congenital hearing loss, after the FDA gave a rapid clearance to its OTOF-targeting medicine Otarmeni.

In a remarkable move, Regeneron has said that Otarmeni (lunsotogene parvec, formerly DB-OTO) – used to treat children and adults with severe-to-profound and profound sensorineural hearing loss (SNHL) caused by OTOF gene variants – will be made available for free to patients in the US.

Typically, gene therapies carry price tags in excess of $1 million, but Regeneron's chief executive, George Yancopoulos, said the company wants to make sure there are no obstacles to access. Making it available for free "serves to highlight our belief that the biopharmaceutical industry can be a genuine force for good in the world," he added.

Patients may still have to bear some out-of-pocket costs for the delivery of the medicine, depending on their insurance coverage.

Otarmeni is an AAV-delivered gene therapy that codes for otoferlin, a protein that allows cells in the ear to sense and transmit sound to the brain, and is administered as a one-shot infusion into the cochlea of the inner ear.

Mutations in the OTOF gene are seen in around 1% to 5% of deafness cases, depending on the population studied, with some estimates suggesting there are 200,000 people affected worldwide.

Until now, there were no approved medicinal treatments for this form of SNHL, which typically causes profound deafness from birth, with most patients using cochlear implant hearing aid devices to improve sound perception and speech recognition.

In the main phase 1/2 CHORD trial supporting the FD's approval of Otarmeni, recently published in the New England Journal of Medicine, nine of 12 deaf children who initially received the gene therapy saw their hearing improve sufficiently to stop using cochlear implants, with three restoring their hearing to normal ranges.

"I've witnessed firsthand my trial participant responding to their mother's voice, dancing to music and interacting with the world, " said CHORD investigator Eliot Shearer of Boston Children's Hospital and Harvard Medical School. "These moments are now possible for more children born with this specific form of hearing loss."

Otarmeni was approved under a Commissioner's National Priority Voucher (CNPV), and is only the second new molecular entity (NME) to be cleared under the new pathway – after Eli Lilly's oral weight-loss therapy Foundayo (orforglipron) – and the first gene therapy to go down this regulatory route.

The CNPV programme can lead to approval just weeks after filing, and is designed to bring important new therapies to patients more quickly.

Regeneron gained rights to Otarmeni when it acquired Decibel Therapeutics for $109 million in 2023, and has beaten various other groups developing OTF-targeted gene therapies to market, including Eli Lilly, Sensorion and Refreshgene, which have candidates in phase 1/2 testing.

MFN deal reached with Trump

The approval came just ahead of Regeneron's announcement of its long-anticipated Most Favoured Nation (MFN) pricing deal with the Trump administration, referencing prices in other developed countries, in return for avoiding tariffs. It includes the agreement to provide Otarmeni for free.

Regeneron is the last of 17 pharma companies sent a letter by Trump last year, ordering them to offer MFN pricing for Medicaid or face tariffs on drugs imported into the US of up to 100%, to finalise a deal.

Along with a previously announced commitment to spend $9 billion on manufacturing and R&D capital investment projects in the US, Regeneron will also make its cholesterol-lowering drug Praluent (alirocumab) available for direct patient purchase at MFN pricing through the TrumpRx.gov channel and will offer Medicaid prices at MFN levels for its current and future medicines.

Photo by Zoe Graham on Unsplash.