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Don't Shout Yet: Drug To Regenerate Hearing Shows Early But Muted Promise In New Trial

A man wears a hearing aid in this 2015 photo. (Matthew Horwood/Getty Images)
A man wears a hearing aid in this 2015 photo. (Matthew Horwood/Getty Images)

A lifetime of jet engines, firecrackers, and concerts can wreak some mayhem on your hearing. Over the years, everyone loses some sensory hair cells in the inner ears, the cells that allow you to detect sound. Once your sense of hearing is damaged, it never recovers.

“Once you lose an inner ear hair cell, they’re gone,” says Dr. Susan King, a neurotologist at the University of Texas Health Science Center. “It doesn’t come back on its own.”

But King is studying a new drug with Woburn-based biotech company Frequency Therapeutics that might allow people to regenerate sensory hair cells — and their sense of hearing. Although there’s still years of work to go, King says preliminary data released Sunday from the company’s early phase clinical trial show the drug’s preliminary promise and tentative evidence it stimulated hearing regeneration in humans for the first time.

“I think this is the first clinical trial that has shown improvement in hearing,” she says. “I have to say, it’s been very energizing for me personally to be part of this exciting research and feel very grateful that I can be part of it.”

“Once you lose an inner ear hair cell, they’re gone. It doesn’t come back on its own.”

Dr. Susan King

Other researchers aren’t making a racket about the results just yet, noting the study’s small size.

“If it works, it’d be fantastic. We’d all be thrilled,” says Dr. Bruce Gantz, an otolaryngologist at the University of Iowa who was not involved with the work. “But it’s such a limited amount of data. I would be very cautious until I did a phase 3, randomized, controlled clinical trial to figure out if it really works.”

The drug, called FX-322, is a combination of two molecules that affect specialized cells called progenitor cells in the inner ear. These cells are the source of ear sensory hair cells, but they lie dormant once the ear is finished developing. One molecule in FX-322 acts like the ignition key in a car, unlocking the genes necessary for growth. The other molecule steps on the gas pedal, activating the progenitor cells.

“That’s the major discovery. It’s the combination to get those progenitor cells to start dividing and growing new cells,” says Carl LeBel, Frequency Therapeutics’ chief development officer.

For the study, the researchers injected FX-322 into one ear of 15 participants, and another eight participants received a placebo. Then, the scientists measured the participants’ hearing ability 15 days, 30 days, 60 days and 90 days after the treatment using a few tests. The first just tests to see how well the subjects can hear tones at different frequencies and loudness. In the others, a recording plays random words and the participants have to repeat the words. In a separate test, the words are played over a distracting, background babble. The researchers tally up how many words the participant got correct.

LeBel says that for four participants, that word score improved significantly after the treatment. When the researchers followed up with the four patients one to two years after receiving treatment, they had still sustained most of that improvement.The other participants who received FX-322 also did better after the treatment, but the difference was only slight.

“In a few individuals, we could double word scores. If an individual came in at start and understand 20 out of 50 correctly, at the end they would get 40 out of 50,” LeBel says. “And they gained about a 10 decibel improvement at the highest frequency we tested. If you gain 10 decibels, that means the difference between being able to hear the water running or the leaves rustling or the birds chirping. You can hear it after treatment and not before.”

“If it works, it’d be fantastic. We’d all be thrilled. But it’s such a limited amount of data. I would be very cautious until I did a phase 3, randomized, controlled clinical trial to figure out if it really works.”

Dr. Bruce Gantz

The improvement was limited only to the ear that received the treatment, and none of the participants who received a placebo saw any gain, either.

But Dr. Alan Cheng, an otolaryngologist at Stanford University who did not work on the study, says there isn't enough evidence to show the drug is truly regenerating sensory hair cells. While Frequency scientists have shown that FX-322 can regenerate sensory hair cells in mice and in the lab, he says there’s still a long road ahead to demonstrate it works in living human beings.

"This is indeed one of the first new therapies to show some functional gain, so this is cool and exciting as a clinician, but it's an incomplete set of data. There's some marginal improvement in hearing but is it regeneration? Well, you can't do a biopsy of the human inner ear, so you can't know," says Cheng, who is also on the scientific advisory board for Boston-based Decibel Therapeutics, another biotech focusing on genetic therapies for hearing.. "The jury is still out whether this drug can truly regenerate cells in the mature mammalian ear."

An improvement of 10 decibels at 8000 hertz is also almost a negligible gain, adds University of Iowa's Gantz, "within test, retest variability of an audiogram," he says.

The participants who saw the greatest benefit from FX-322 also had the most severe hearing loss, says UT Health Science Center’s King. The other participants only had mild hearing loss, and thus did not have much room to improve. Though, she agrees, the work is still only preliminary. She and her collaborators are currently working on a larger, phase 2 clinical trial for FX-322

“These are early results, so we don’t want to overstate,” she says. “If this pans out though, this really has the potential to help a lot of people because there truly isn’t a treatment for sensory neural inner ear loss.”

Cochlear implants and hearing aids only go so far, she adds. But the data they’ve generated so far, she says, makes her believe there’s a good chance FX-322 might allow people to regenerate their own hearing.


Correction: An earlier version of this story stated these data are from a phase 1 clinical trial. It is from an early phase clinical trial that includes aspects of both traditional phase 1 and phase 2 clinical trials.

This article was originally published on September 13, 2020.

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Angus Chen Reporter, CommonHealth
Angus Chen was a reporter for WBUR's CommonHealth.

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