Brimapitide (AM-111)

Human clinical Neuroprotection 3 sources

Brimapitide (AM-111) is a cell-permeable peptide that inhibits the c-Jun N-terminal kinase (JNK) pathway, which is involved in stress-induced cell death. It has been primarily researched as an intratympanic injection for the treatment of acute sensorineural hearing loss. While early trials showed promise in protecting inner ear hair cells from apoptosis, later Phase 3 trials yielded mixed results, though it remains a compound of interest for inner ear neuroprotection.

01Dosing reference

Amount

0.4 mg/mL or 0.8 mg/mL (in clinical trials)

Frequency

Single dose

Cycle

Administered once within 72 hours of acute hearing loss onset

Reference figures, not a recommendationThese values reflect amounts described in the literature and vendor documentation this database indexes. Use the reconstitution calculator to convert them into syringe units.

02Mechanism of action

JNK Pathway Inhibition

Brimapitide binds to the JNK-interacting protein (JIP) scaffold, preventing the activation of c-Jun N-terminal kinase (JNK).

Prevention of Apoptosis

By blocking JNK activation, it prevents the downstream signaling cascade that leads to stress-induced apoptosis (programmed cell death) in inner ear hair cells.

Otoprotection

This cellular preservation translates to potential protection against permanent hearing loss following acute acoustic trauma or sudden deafness.

03Human evidence

Phase 2 clinical trials showed that intratympanic administration of AM-111 was well-tolerated and provided a statistically significant improvement in hearing recovery in patients with severe to profound sudden sensorineural hearing loss.

Phase 2 trial, randomized, double-blind, placebo-controlled.

In the Phase 3 HEALOS trial, AM-111 did not meet its primary efficacy endpoint for the overall study population, though post-hoc analysis suggested potential benefits in a subpopulation with profound hearing loss.

Phase 3 trial, large patient cohort, limited by the failure to meet the primary endpoint across all severities.

04Preclinical evidence

Animal models of acute acoustic trauma demonstrated that local administration of AM-111 significantly reduced the loss of sensory hair cells and preserved hearing thresholds.

Guinea pig and chinchilla models of noise-induced hearing loss.

In vitro studies showed that AM-111 effectively blocked JNK-mediated apoptosis in various cell types exposed to oxidative stress and excitotoxicity.

Cell culture models, limited by translation to complex in vivo pharmacokinetics.

05What is known vs. unknown

Reasonably established

Brimapitide is a synthetic peptide designed to inhibit the JNK stress kinase pathway.
It is formulated for local (intratympanic) delivery to target the inner ear directly.
Research has heavily focused on its potential to treat acute sensorineural hearing loss and tinnitus.
It contains a TAT sequence (trans-activator of transcription) that allows it to easily cross cell membranes.

Unknowns & limits

The exact therapeutic window (how soon after injury it must be administered) remains a significant clinical challenge.
Phase 3 clinical trials failed to show broad efficacy, leaving its future regulatory approval uncertain.
Long-term effects of JNK inhibition in the inner ear are not fully understood.

06Safety & regulatory context

Regulatory statusBrimapitide has generally been well-tolerated in clinical trials when administered via intratympanic injection, with adverse events mostly related to the injection procedure itself (e.g., transient middle ear pain or mild vertigo). It is not FDA-approved for any indication. Its development has faced setbacks due to mixed Phase 3 efficacy results, and it remains an investigational compound primarily studied in the context of acute inner ear disorders.

07Compared with Corticosteroids

Brimapitide (AM-111) vs. Corticosteroids

Key difference

Corticosteroids act as broad anti-inflammatory agents, whereas Brimapitide specifically targets the JNK apoptotic pathway to prevent cell death.

When researchers discuss each

Corticosteroids are the current standard of care for sudden sensorineural hearing loss, while Brimapitide is discussed as a targeted, experimental neuroprotective alternative or adjunct.

08Glossary

JNK (c-Jun N-terminal kinase)

An enzyme that plays a key role in triggering cell death in response to stress, such as loud noise or lack of oxygen.

Apoptosis

Programmed cell death, a process that Brimapitide aims to prevent in damaged inner ear cells.

Intratympanic injection

A procedure where medication is injected directly through the eardrum into the middle ear to reach the inner ear.

09Knowledge check

Q1What is the primary mechanism of action of Brimapitide (AM-111)?

Q2How is Brimapitide typically administered in clinical trials for hearing loss?

Q3Which of the following describes a documented limitation of the clinical evidence for Brimapitide (AM-111) as presented in the dossier?

Q4When researchers compare Brimapitide (AM-111) with corticosteroids for sudden sensorineural hearing loss, which statement best reflects the comparison context given in the dossier?

Q5Which statement most accurately reflects the safety and regulatory context for Brimapitide (AM-111) reported in the dossier?

10Sources

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Research and educational use onlyNothing on this site is medical advice, a prescription, or a recommendation for human use. Compounds documented here are research chemicals. Consult a qualified clinician before making any health decision.