AC102, ein innovatives Molekül, das in präklinischen Modellen eine starke Wirksamkeit gegen Hörverlust zeigt, befindet sich nun im fortgeschrittenen Stadium der Phase 2

Introduction

Although not approved, glucocorticoids are recommended by guidelines to treat Sudden Sensorineural Hearing Loss (SSNHL). This doctrine was questioned by latest results from a Germany-wide trial in idiopathic SSNHL patients (Plontke et al., 2024): High doses of glucocorticoids were not superior to standard dose. Besides that, up to 52% of patients required a hearing device at study end. These results call for new treatments.

Methods

AC102, formulated in a thermosensitive gel, is developed to treat hearing loss.

Model of Noise-induced hearing loss (NIHL): Guinea pigs were overexposed to noise and treated with AC102, placebo or dexamethasone 1h after trauma. Hearing was assessed by ABR at D21Phase 2 (AC102-201): Efficacy of single i.t. application with AC102 compared to oral prednisolone (60 mg/mL) in 210 patients with idiopathic SSNHL in 8 countries. Main endpoints: Improvement in hearing threshold (D28) and word recognition (D84)

Results

Following NIHL, AC102 reversed hearing thresholds in guinea pigs to almost normal levels across frequencies (2-32 kHz). The effect of dexamethasone was comparable to placebo. Histology revealed that AC102 restored ribbon synapses and outer hair cells, structures damaged during hearing loss.

AC102 was reported to be safe and tolerable in a Phase 1 trial in healthy volunteers and by the Data Safety Monitoring Board (DSMB) in the ongoing Phase 2 in idiopathic SSNHL patients.

Discussion

In an NIHL model, AC102 outperformed glucocorticoids, the current SoC for treatment of hearing loss. It showed a positive safety profile in a Phase 1 trial in healthy volunteers. This was confirmed by the DSMB in an ongoing Phase 2 in SSNHL patients, which evaluates the efficacy of AC102.

Plontke et al.,(2024); NEJM Evid 3(1)

S. Plontke declares research grants to University (Coordination Investigator Clinical Trial)

R. Schlingesiepen is the CEO of AudioCure Pharma GmbH, Sponsor of clinical study AC102-201