Hearing loss treatment moves forward despite early disappointment

NEW YORK, Dec. 5 (UPI) -- An innovative approach to treating hearing loss might be closer to reaching the market, despite a setback in the testing process, the researchers behind the technology say.

In early clinical trials, a drug known as FX-322 produced significant improvement in speech perception in several participants with noise-induced hearing loss after a single injection into the inner ear -- with some reporting benefits that lasted as long as two years, according to its developer, Frequency Therapeutics of Lexington, Mass.

Its drug candidate, FX-322, is designed to be injected in microscopic amounts into the inner ear. People with hearing loss can receive one or more injections, depending on the severity of their symptoms.

The company said the drug is intended to stimulate the growth of hair cells in the cochlea that enable hearing after those cells have died off.

While preliminary trials appeared to do that, participants in Phase 2 efficacy trials with mild to moderately severe inner-ear hearing loss caused by noise exposure, advancing age and other factors -- who received four weekly injections -- did not experience improvement in some measures of hearing, the company said.

And although study participants did see improvement as measured by word recognition scores, repeated weekly injections appeared to reduce the benefits compared with a single injection, it said.

The company blamed design of the study and not the drug for the disappointing results, Kevin Franck, its senior vice president of strategic marketing and new product planning, told UPI in a Zoom call.

"There has never been a drug to treat hearing loss, and these measures have never been put to the test in a placebo-controlled trial, because you can't do a placebo-controlled study with hearing devices -- you either get the device or you don't," said Franck, who also is a trained audiologist.

"Every time we did [a study], we were breaking new ground, so, of course, there are going to be setbacks," he said.

Still, as a publicly traded company, Frequency Therapeutics, which described the negative results as "unexpected," saw its share prices plummet in the weeks that followed. Shares had peaked at $54 on Feb. 22, 2021, on strong expectations, but rapidly fell starting in March 2021 and remain just above $2.

Frequency Therapeutics had a net loss of $64.2 million for the nine months ended Sept. 30. Such losses are typical for startup companies without a product on the market, analysts said.

Almost 25% of its shares are held by institutions, led by The Vanguard Group with 5% and Blackrock with 4.2%, according to Yahoo Finance.

As noted in its corporate profile, the company has a license and collaboration agreement with Astellas Pharma for development and commercialization of FX-322, as well as collaboration and licensing agreements with Massachusetts Eye and Ear, the Massachusetts Institute of Technology, The Scripps Research Institute and Cambridge Enterprises.

With investors concerned about the viability of FX-322, the company faced potential funding challenges, but its executives said they remained confident in the technology.

"We weren't going to let one problem with study design throw off the promise of a drug that's got so much potential to help a lot of people," Franck said.

Frequency Therapeutics is the midst of new Phase 2 trials for individuals with noise-induced hearing loss and other forms of sudden deafness, with results expected in the first quarter of next year, according to a news release.

If the studies find the drug provides some benefit for people with hearing loss, the next step would be to initiate Phase 3 clinical trials for efficacy, with more participants.

If those trials show positive results, it would be up to the Food and Drug Administration to decide whether they are convincing enough to approve marketing the drug.

Welcome treatment

A new treatment for hearing loss would be welcome news to millions of people in the United States. Nearly one in five adults age 20 to 69 has hearing loss in one or both ears, according to the National Institute on Deafness and Other Communication Disorders.

The risk for hearing loss increases with age, with up to 25% of those age 65 to 74 and 50% of those age 75 and older living with disabling hearing loss, research suggests.

Sensorineural hearing loss is caused by damage to the structures in the hair cells and other structures in the inner ear or the auditory nerve caused by noise exposure, genetic factors or the natural aging process, the national institute says.

And that accounts for more than 90% of hearing loss in adults, it estimates.

The initial trials of FX-322 focused on participants with sudden idiopathic hearing loss, or hearing loss that occurs suddenly, with no apparent cause, and noise-induced hearing loss, according to Frequency Therapeutics.

However, for Phase 2 trials in which the drug did not perform as well, the FDA had asked the company to include participants with age-related hearing loss and no history of noise exposure, Franck said.

This is because this form of hearing loss is so common, he said.

The company also included participants with severe hearing loss due to noise exposure.

"It's true [these studies] didn't show as robust a response, because we're looking at really different things," Franck said of the results released in March 2021.

In addition, flaws existed in the trial design process, which showed up in several ways, including that participants given a placebo reported improvements in hearing scores, Franck said.

This was attributed to bias in the participant recruitment process -- essentially, participants were told in advance that the drug being studied would treat their hearing loss and they responded accordingly, the company said.

Options for treatment

The primary treatments for all forms of hearing loss, hearing aids and cochlear implants, can help lessen the symptoms of the condition, but do not address its underlying causes, otolaryngologist Jourdan T. Holder told UPI in an email.

"Both are highly effective at improving speech understanding and quality of life," said Holder, director of the cochlear implant program at Vanderbilt University Medical Center in Nashville.

"A cochlear implant should be considered for anyone who does not feel that they benefit from appropriately fitted hearing aids," she said.

Although hearing aids have become more effective, as well as smaller and less cumbersome, people are still reluctant to use them for cosmetic reasons, otolaryngologist Dr. Yin Ren told UPI in a phone interview.

As a result, fewer than one in three adults age 70 and older with hearing loss uses hearing aids, according to the National Institute on Deafness and Other Communication Disorders.

Meanwhile, cochlear implants, though generally safe, require surgery, which discourages some people, said Ren, an assistant professor of otolaryngology at Ohio State University and a physician at Wexner Medical Center in Columbus.

A less invasive approach

But this is where a new form of treatment might find a niche. That's because hair cells die after exposure to loud noises or drugs, including certain chemotherapies and antibiotics, Holder said.

"Hearing devices like hearing aids and cochlear implants are designed to make things louder, and louder helps make things clearer for people with hearing loss," Franck said.

"But over time, we know that in people with hearing loss, the cochlea loses resolution, and currently available devices don't bring that back."

Researchers with Frequency Therapeutics believe a drug that regenerates hair cells and reverses the loss of resolution in the cochlea "would be the holy grail" of hearing loss treatment, Franck added.

FX-322, and its sister drug, FX-345, seek to prove just that.

In clinical trials to date, the drugs have proved safe, with only mild side effects -- mostly pain and itching at the injection site, the published studies found.

"There were no drug-related severe adverse events in over 200 people," Franck said.

The only question that remains is what type of hearing-loss patients will benefit most from the drug, he said.

The current trial, for which participant enrollment has been completed, focuses on people with noise-induced hearing loss and sudden, "inner ear" hearing loss, or sudden deafness, an unexplained, rapid loss of hearing either all at once or over a few days.

Unlike the earlier Phase 2 studies, those with age-related hearing loss are not included.

If all goes well, the company plans to submit data from the current trial in early 2023 and begin Phase 3 trials soon after.

Holder and Ren suggest that the drug could prove to be a "game-changer," as Ren puts it, because it is less invasive and more convenient than current treatments, while treating the underlying causes of hearing loss.

Unlike cochlear implants, for example, FX-322 and FX-345 do not require surgery, and the drug's recipients show no outward signs of treatment, as they would with hearing aids.

"The future of this technology is promising," Holder said. "However, the best hearing loss intervention is the one available now."

She added: "Individuals should not delay treatment with hearing aids or cochlear implants in favor of waiting for new injectable treatment options to become available because it is important to keep the auditory nerves and the auditory portion of the brain stimulated."