Frequency Therapeutics Inc (Nasdaq: FREQ) today announced topline, day-90 data from its recent study, showing that four weekly injections of its FX-322 treatment therapy in subjects with mild to moderately severe sensorineural hearing loss (SNHL) did not demonstrate improvements in hearing measures versus placebo. FX-322 is Frequency’s lead product candidate, designed to regenerate auditory sensory hair cells in the cochlea and improve hearing in patients with SNHL. In February, the company announced the publication of its FX-322 Phase 1/2 study results in Otology & Neurotology which indicated hearing improvements in adults with acquired SNHL and the “first known linkage of pharmacokinetics and pharmacodynamics for a potential hearing restoration therapy.” That news caused a wave of excitement, and even resulted in the decline of many hearing aid stocks.

The most recent FX-322 Phase 2a study (FX-322-202) did demonstrate no treatment-related serious adverse events in the study. Frequency also announced new data from a parallel study demonstrating hearing improvement from a single injection of FX-322. The company plans to advance further development of FX-322 as a single-dose regimen.

In the FX-322-202 study, 95 subjects aged 18-65 were evaluated for hearing improvement using word recognition, Words-In-Noise (WIN), pure-tone audiometry, and additional exploratory measures. All subjects were administered a total of four weekly intratympanic injections comprised of zero, 1, 2, or 4 doses of FX-322, with the balance of injections comprised of placebo doses. While WR scores increased across all groups, repeated weekly injections appeared to dampen the hearing benefit observed compared to other single-injection studies. The Phase 2a interim results also showed an unexpected apparent level of hearing benefit in the placebo group that did not occur in previous trials and exceeded well-established published standards, potentially suggesting bias due to trial design. Given these challenges observed in the Phase 2a study design, there was no discernible hearing benefit of FX-322 over placebo.

“Our FX-322 interim Phase 2a clinical results were unexpected, especially given our prior published Phase 1/2 data,” said Frequency’s CEO David L. Lucchino. “We have already gained important learnings from this study that will inform our future development efforts. The results clearly demonstrated that a treatment regimen using four weekly injections is unfavorable and we will continue to move ahead with single-dose administrations in future studies. We believe in the potential of FX-322 given the demonstrated hearing signal and favorable safety profile observed with a single dose and in the future, we may evaluate re-treatment at longer intervals.”

The company also announced preliminary results today from a recently completed open-label, single-dose study of FX-322 (FX-322-111) designed to evaluate the impact of injection conditions on tolerability. In the multi-center, randomized study, 33 subjects with mild to severe SNHL were injected in one ear with FX-322, with the untreated ear as the control. Hearing function was tested over the course of 90 days following dosing. At day 90 following dosing, 34% of subjects achieved a 10% or greater absolute improvement in WR scores in the treated ear, which was clinically meaningful and statistically significant compared to the untreated ear (p <0.05). This included a subset of subjects that more than doubled their WR scores. The single dose had a favorable safety profile and was well tolerated. These latest results are supportive of the data reported in the prior single dose Phase 1/2 (FX-322-201) study, recently published in the peer-reviewed journal Otology & Neurotology.

“We now have two independent, single-dose studies showing a hearing signal with FX-322 and with statistically significant improvements in speech intelligibility,” says Lucchino. “More single dose studies are underway to further understand the potential benefit of FX-322 in additional patient populations. Frequency is well resourced, and with the support of our collaborator Astellas Pharma, we will continue to advance development of potential hearing restoration therapeutics for the millions of individuals impacted by sensorineural hearing loss. We are very thankful to the people who participated in our studies and to the staff at all of the sites for their contributions and continued engagement, especially during the pandemic.”

FX-322 Ongoing Development Activities

According to Frequency, clinical development activities are ongoing to evaluate FX-322’s clinical profile in patients with age-related hearing loss (ARHL) and severe SNHL, to identify additional patient populations that may benefit from this potentially restorative therapeutic approach. This includes a double-blind, placebo-controlled Phase 1b study (FX-322-112) of subjects with ARHL (ages 66-85), which is fully enrolled with 30 subjects. The primary objectives of the Phase 1b ARHL study are to assess the local and systemic safety of a single dose of FX-322 and evaluate hearing responses in an older adult cohort. Study participants were randomized 4:1 to receive either FX-322 or placebo in one ear. Validated measures of hearing including WR, WIN and pure tone audiometry were used. Safety, otologic and audiologic assessments were conducted at days 30 and 90 following administration of FX-322 or placebo. Frequency expects to share results from this study in Q2 2021.

Frequency is also conducting an FX-322 Phase 1b study of up to 30 subjects ages 18-65 with severe SNHL (FX-322-113). This study, which has a similar study design as the ARHL study, is continuing to enroll subjects and results are anticipated in Q3 2021.

The company plans to report final results of the Phase 2a study in late Q2 2021.

Source: Frequency Therapeutics and Hearing Review