Inner Ear Therapeutics

Altamira (through its subsidiary Auris Medical) has three clinical programs for the treatment of inner ear disorders:

Betahistine is widely used around the world for the treatment of vestibular disorders. The molecule is a structural analog of histamine. It acts as a partial histamine H1-receptor agonist and, more powerfully, as a histamine H3-receptor antagonist. Betahistine has been shown to increase cochlear, vestibular and cerebral blood flow, facilitate vestibular compensation and inhibit neuronal firing in the vestibular nuclei. Unlike other vertigo drugs, it has no sedating effect.

Various studies have demonstrated therapeutic benefits of betahistine in both the treatment of vertigo as well as in supporting vestibular rehabilitation. However, the evidence for therapeutic benefits is variable, and it is well known that orally administered betahistine is rapidly and almost completely metabolized. As a consequence, the bioavailability of oral betahistine is very low.

AM-125 is being developed for intranasal administration of betahistine to improve its bioavailability as more active substance can be taken up via the nasal mucosa. Preclinical and clinical data confirm that AM-125 increases betahistine levels in the blood circulation 5 to 29-fold compared to a standard oral dose of betahistine. In a recent Phase 2 clinical trial in patients suffering from acute vestibular syndrome following surgery, AM-125 showed a dose- and time-dependent improvement of balance and signs and symptoms of vestibular dysfunction. Altamira plans to submit a request for an IND shortly and to continue clinical development of AM-125 through partnering.   

Sonsuvi^® is being developed for the treatment of acute sensorineural hearing loss (ASNHL), where there is damage to the sensory cells of the inner ear. ASNHL may be triggered by a variety of insults, such as exposure to excessively loud sound, infection, inflammation or certain ototoxic drugs. There are currently no approved treatments for this patient population.

Sonsuvi^® contains a synthetic D-form peptide (Brimapitide or D-JNKI-1) that protects sensorineural structures in the inner ear from stress-induced damage. It has been granted orphan drug status by both EMA and FDA and has been granted fast track designation by the FDA for the treatment of sudden sensorineural hearing loss. Sonsuvi^® is administered in a single dose by intratympanic administration within the first three days from ASNHL onset.

In a Phase 3 clinical trial (HEALOS), Sonsuvi^® showed a clinically meaningful and nominally significant improvement in hearing thresholds in the Sonsuvi^® 0.4 mg/mL treatment group compared to placebo for patients with profound ASNHL (essentially unable to hear anything; pure tone average ≥ 90 dB). Altamira discussed and agreed with the EMA and FDA a protocol for another Phase 3 clinical trial to confirm these promising outcomes. Such study shall be conducted with a partner.

Tinnitus, frequently perceived as a ringing in the ears, is the perception of sound when no external sound is present. Similar to pain, it is an unwanted, unpleasant and thus distressing sensation. Tinnitus may result in further symptoms such as inability to concentrate, irritability, anxiety, insomnia, and clinical depression. In many cases, tinnitus significantly impairs quality of life and affects normal day-to-day activities.

Acoustic trauma and other insults to the inner ear may trigger increased levels of extra-cellular glutamate, which in turn cause excessive activation of cochlear NMDA receptors. This process results in damage or killing of sensory cells and is thought to be responsible for abnormal spontaneous “firing” of auditory nerve fibers, which may be perceived as tinnitus.

Keyzilen^®, Esketamine gel for injection, has been developed for the treatment of acute inner ear tinnitus. Esketamine is a potent, small molecule NMDA receptor antagonist. Keyzilen^® is administered via 3 intratympanic injections over 3-5 days. In two Phase 2 clinical trials, Keyzilen^® demonstrated a favorable safety profile and positive effect on subjective tinnitus loudness and other outcomes. Design issues in two Phase 3 clinical trials resulted in inconclusive outcomes. Based on learnings from these trials, Altamira has designed a concept for further clinic development, which was reviewed with the FDA and EMA. Further studies shall be conducted with a partner.