Frequency Therapeutics Abandons Hearing Loss Treatment Programs

Frequency Therapeutics Inc, a Lexington, Mass-based biotech focused on regenerative medicine, has announced it will no longer pursue its FX-322 and FX-345 programs designed to help people with sudden or noise-induced sensorineural hearing loss (SNHL).

The decision by the company was made following a disappointing Phase 2b study involving FX-322 that provided no measurable improvements in 142 people with sudden or noise-induced SNHL. Although there were no adverse effects from the FX-322, there were also no statistically meaningful differences in speech perception after 90 days between those administered with FX-322 versus those receiving a placebo.

Frequency will now discontinue its FX-322 development program. Additionally, while FX-345—a second candidate to treat SNHL—has completed an initial safety Phase 1b trial, that program will also be discontinued.

“This was a rigorous and well-designed study that provided us a clear outcome, though not the outcome we wanted,” said Frequency Chief Scientific Officer Chris Loose, PhD, in a press statement. “Given these disappointing results, we will cease further development of the company's drug candidates for hearing loss. We are thankful to the patients, clinicians and their staff, and the experts from our clinical advisory board who helped us to design and run a conclusive study in SNHL. We hope the learnings from our studies will benefit the field and ultimately support the successful development of future treatments for hearing loss."

The company now plans to focus its resources on advancing its treatment for remyelination in Multiple Sclerosis (MS) patients. It will immediately reduce headcount as part of an overall restructuring, downsizing personnel by approximately 55%. The company believes that the restructuring will generate sufficient cost savings to extend its runway into 2025 and enable it to complete the first clinical trial of its MS program in the second half of 2024. At the end of 2022, Frequency reported cash, cash equivalents, and marketable securities of $83.1 million (excluding restricted cash).

Second drugmaker in four months to throw in the towel on hearing loss treatment

The discontinuation of Frequency Therapeutic's two drug candidates is a blow to those hoping for biotech solutions for hearing loss. Not only did Frequency have two exciting treatment candidates, but the demise of FX-322 and FX-345 comes on the heels of another high-profile company that scuttled its hearing loss treatment programs.

Exactly four months ago, Otonomy reported disappointing results on its OTO-413 and OTO-825 programs for congenital hearing loss. Although OTO-413 had previously demonstrated promise in two separate patient groups that received a single lower-dose unilateral drug injection, a study with higher doses did not show clinically meaningful improvements for patients. This was preceded by Otonomy announcing in August 2022 that its lead drug candidate at that time, OTO-313—designed to help people with tinnitus—demonstrated no meaningful improvement versus placebo. On December 15, Otonomy decided to shut its doors.

Still, lots of progress in the past year

Although the exiting of these programs is obviously bad news, substantial progress continues to be made in developing drug, gene, and stem cell treatment therapies for hearing loss. More than a dozen companies and institutions are racing for solutions. And some are making excellent progress.

For example, in October, Fennec launched the first hearing loss-related drug to be approved by the FDA. Called Pedmark, the new sodium thiosulphate compound has been shown to reduce the risk of hearing loss in children undergoing Cisplatin chemotherapy.

In November, the FDA granted Sensorion's OTOF-GT gene therapy a “Rare Pediatric Disease Designation” for treating otoferlin gene-mediated hearing loss. Patients with OTOF mutations suffer from severe-to-profound prelingual SNHL. Otoferlin deficiency is one of the most common forms of congenital deafness, responsible for up to 8% of all cases of congenital hearing loss for about 20,000 people in the United States and Europe.

Both Fennec and Sensorion have competitors developing similar treatments (Decibel and Akouos, respectively), demonstrating that this is a hot area for research.

As noted in a recent HearingTracker article, there's unlikely to be one "eureka" or breakthrough moment in the race to develop hearing loss treatments. Instead, hearing loss treatments will probably continue to chip away at specific types of hearing problems and offer solutions for repairing, restoring, or regenerating hair cells and nerve fibers. In this way, it may follow much the same pattern of success in cancer treatments.