Last year was a busy and eventful one for Frequency Therapeutics, the Boston-based biotech company working on FX-322, a drug candidate in clinical trials to potentially restore sensorineural hearing loss. The company has learned some interesting lessons from clinical trials of FX-322 conducted in 2021, and has also introduced a new clinical candidate, FX-345, that they hope will be able to get even deeper into the cochlea – potentially enabling treatment of different populations of patients with acquired hearing loss.
So far, Frequency has run 4 clinical trials of FX-322 in phase 1, which is the first step towards developing a drug approved by the Food and Drug Administration (FDA) to be used to treat a given condition. In phase 1, researchers test for drug safety and the maximum effective dose of a drug in humans. The company has run 5 trials to date and has just begun their largest, a new phase 2b study.
Results of Previous FX-322 Clinical Trials
Frequency has thus far found in three separate studies that hearing improvements can be seen following a single administration of FX-322, when testing participants’ hearing 90 days following dosing to see if their speech perception measures increased. These participants had hearing loss ranging from mild to severe. “Speech perception is important because that’s what people with hearing loss have told us is the critical unmet need. They said, ‘We struggle to hear conversations, particularly in noise,'” says Kevin Franck, PhD, Senior Vice President of Strategic Marketing and New Product Planning.
When tested, some participants showed an increase in word recognition – in a test of 50 words, the highest was an increase of 20 words, or a 40 percent increase in the words recognized. The drug was well-tolerated in people. And in a separate study, the company re-tested the hearing of participants who had received the drug a year or two prior. “Some of those people continued to have that benefit [of increased word recognition], which makes sense, because we believe we’re restoring some of the original biology – and that original keeps working,” Dr. Franck adds.
A Game-Changing Possibility
These results represent potentially a huge advance in the field of hearing restoration. “This is suggesting that the drug could be disease-modifying – so you’re actually correcting the underlying condition,” says Carl LeBel, PhD, Frequency’s Chief Development Officer. “And we can’t think of a single example where you’ve given one dose of an agent, you produce an effect, and that effect lasts for this long.”
So far, the company has had the most success in treating people who have sudden sensorineural hearing loss with no known cause (meaning not caused by trauma or another obvious factor), as well as people with noise-induced hearing loss. Together, these fall into the category of acquired adult sensorineural hearing loss. “Where we have the most confidence about the percentage of responses is in moderate to moderate- severe range due to noise and sudden hearing loss,” Franck says. “And that’s the group that we’re using to study this next clinical trial that’s underway.”
This isn’t to say that the company is ignoring other hearing loss populations, such as those with age-related hearing loss, or those who are given drugs that diminish hearing, such as certain cancer patients. “We’re going to continue to study them,” says Dr. LeBel. “But for us to get the drug approved as quickly as possible, we want to focus in on the populations that have shown the greatest response so far.”
How to Learn More about Frequency’s Current Clinical Trial
Frequency’s current clinical trial is a double-blind, placebo-controlled phase 2b study, in which researchers are studying the drug candidate with a larger group of patients to assess effectiveness and further study safety. The company has expanded testing to 27 different sites around the country. To qualify, you need to have noise-induced hearing loss or sudden hearing loss and be between 18 and 65 years old. To see if there is a testing site near you, visit the study’s ClinicalTrials.gov page. There is also a separate website with a questionnaire to see if you qualify for the study.
FX-345: Another Clinical Trial to Come
The company is also working on a new clinical candidate for hearing restoration, called FX-345, which is designed to go further into the cochlea to potentially activate more progenitors to restore hearing function. FX-345, like FX-322, is a combination of two drugs that Frequency believes are required to activate cells in the cochlea to divide and then form new hair cells. “What we have done is taken one of those drugs, and we’ve swapped in a new drug that goes after the same target, but that new drug is much more potent than the one that’s currently in FX-322,” LeBel says.
Because of the activity of the drug and its concentration, researchers believe that they may be able to restore some of the lower frequencies in the cochlea, not just the high frequencies that are on the outer part. “So the might open up the door that some of the folks that aren’t responding to FX-322 for whatever reason,” LeBel adds. Clinical trials for FX-345 are expected to start in the second half of 2022.