Meta-analysis shows oral betahistine combined with Epley maneuver reduces dizziness in posterior canal BPPV patients

Altamira Therapeutics, a company that develops RNA-based therapeutics, reports highlights from a peer reviewed article showing the efficacy of oral betahistine in the treatment of posterior canal benign paroxysmal positional vertigo (BPPV) when administered along with a canal repositioning procedure, the Epley maneuver.

The article was published in the journal Medicine and describes the results from a meta-analysis of nine randomized controlled trials with 860 posterior canal BPPV patients, of which 432 were treated with Epley’s maneuver plus betahistine, and 428 solely underwent Epley’s maneuver. According to the meta-analysis, Epley’s maneuver plus the use of betahistine resulted in a significantly greater reduction in dizziness handicap as measured by the Dizziness Handicap Inventory (DHI) compared to Epley’s maneuver alone (p = 0.001).

Betahistine is a small molecule structural analog of histamine and acts as an agonist at the H1 histamine receptor and as an antagonist at the H3 histamine receptor, report experts. Unlike histamine, it crosses the blood-brain-barrier. Betahistine is known to increase the release of histamine, acetylcholine, dopamine and norepinephrine in the brain. It increases cochlear, vestibular and cerebral blood flow and facilitates vestibular compensation and inhibits neuronal firing in the vestibular nuclei. Betahistine for oral administration is reportedly approved in about 115 countries (with the U.S. being a notable exception) for the treatment of vertigo and Meniere’s disease. Despite its good safety profile, the clinical utility of orally administered Betahistine is limited due to poor bioavailability.

Experts say that BPPV is characterized by repeated episodes of vertigo (dizziness) produced by changes in the head position relative to gravity, e.g. when tipping the head backward. It is typically caused by dislodged inner ear particles (otoconia) in one of the semicircular canals, most often the posterior canal. Reportedly, the debris elicits unwanted vestibular stimulation and is often cleared through physical repositioning procedures such as the Epley maneuver, which is strongly recommended by the Clinical Practice Guideline of the American Academy of Otolaryngology – Head and Neck Surgery. According to the academy, since a patient may experience dizziness and instability for some time even after a successful maneuver, betahistine as an antivertigo drug is frequently administered to help accelerate their resolution.

According to a study published in the journal Otolaryngology – Head and Neck Surgery, BPPV is the most common type of vertigo, which accounts for 17 to 42% of all diagnosed cases. A primary complaint of dizziness accounts for 5.6 million clinic visits in the United States per year. Experts say that patients, suffering from BPPV, experience significant inconveniences and disabilities during symptomatic episodes, as they interfere with day-to-day activities such as driving a car or climbing stairs;BPPV generally emerges in the elderly with a peak onset in the between 50-60 years of age.

Altamira has been developing AM-125, a patented formulation of betahistine for intranasal administration, for the treatment of acute vestibular syndrome (AVS), which may be triggered by a variety of causes including trauma, infection or inner ear fluid disturbances such as in BPPV. The company states that by avoiding the fast metabolism after oral intake, intranasal delivery of AM-125 achieves higher bioavailability of betahistine (5-to-29 times higher). AM-125 has been reportedly tested in a Phase 2 clinical trial (“TRAVERS”) with patients suffering from AVS following vestibular surgery. Researchers noted that compared to placebo, AM-125 treatment helped accelerate vestibular compensation and alleviate signs and symptoms of vestibular dysfunction. The Company expects to file an IND application for intranasal betahistine (AM-125) with the FDA in May 2023, including the protocol for its Phase 2 clinical trial in BPPV.

Thomas Meyer, PhD

“We are pleased to see betahistine’s clinical utility further confirmed in this meta-analysis of several studies in BPPV patients,” commented Thomas Meyer, PhD, Altamira’s founder, chairman and CEO. “Following the positive outcomes in surgery-induced AVS in the TRAVERS trial, we feel vindicated in our choice of BPPV to advance the clinical development program for AM-125. Where marketed, BPPV has traditionally been one of the most frequent indications for oral betahistine. We look forward to submitting the IND application shortly which will be an important milestone on our way to transfer the innovative AM-125 program to one or several partners as we are repositioning the Company around our RNA delivery technology.”

For more information about Altamira, visit the company website.

Source: Altamira

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