Montelukast oral film may help in mild to moderate Alzheimer’s
Treatment led to significant improvements in patients' cognition in trial
The use of Montelukast oral film, an experimental therapy being repurposed by Intelgenx to treat mild to moderate Alzheimer’s disease, led to significant improvements in patients’ cognition versus a placebo in a Phase 2 clinical trial.
That’s according to the findings of a top-line analysis of efficacy data from the now-completed BUENA trial (NCT03402503), and refers to patients treated with a Montelukast dose of 30 mg twice daily. The final analysis, along with all safety and efficacy data from the trial, is expected to be completed and released later this year.
“This preliminary analysis suggests that treatment with [montelukast] 30 mg twice daily … was associated with an experimentally important benefit to cognition. Given this, further study of this … dose with consistent treatment will be of value,” Paul Maruff, PhD, chief innovation officer at Cogstate, a company assessing the trial participants’ cognition through a battery of neuropsychological tests, said in an Intelgenx press release.
Intelgenx obtained these early efficacy results from Cogstate, which developed the testing battery used in the proof-of-concept Phase 2 trial.
Based on this early analysis, Intelgenx announced that the BUENA study has “provided some first human evidence — although preliminary — for the use of [Montelukast oral] film as a treatment modality and option for patients with mild to moderate [Alzheimer’s disease].”
Importantly, however, the summary study results showed that “when considered across all doses of [Montelukast], no benefit to general cognition was observed when compared to change under placebo,” the release stated.
Intelgenx repurposed Montelukast for use as Alzheimer’s treatment candidate
Alzheimer’s disease is the most common cause of dementia, which is characterized by nerve cell death starting in the hippocampus, a brain region related to memory and learning. In the early or mild stages of Alzheimer’s, individuals typically experience problems with remembering new information and may exhibit confusion.
These symptoms become more pronounced as the disease progresses, with patients often needing more help with daily activities, and potentially experiencing personality and mental health issues, in moderate and advanced stages of the disease.
Montelukast is a medication that blocks the production of leukotrienes — molecules that mediate inflammation — by targeting leukotriene receptors, therefore preventing some inflammatory processes. It originally was approved in the U.S. in the late 90s for the treatment of asthma and seasonal allergies.
However, previous research demonstrated that montelukast can increase the production of nerve cell progenitors, which are cells that can differentiate into more than one cell type, including nerve cells, or neurons.
Intelgenx now is reformulating the medication into an oral film using its proprietary VersaFilm technology. The Montelukast VersaFilm may provide advantages over tablets, such as an easier administration mode and absorption into the bloodstream directly from the mouth, allowing for lower doses and less toxicity.
Initial Phase 1 trials indicated that the formulation was safe and well tolerated in healthy individuals, and that its bioavailability — the extent and rate at which a medication reaches the bloodstream — was 52% higher than that of tablets.
The BUENA trial enrolled 59 adults, ages 50 and older, with mild to moderate Alzheimer’s, all of whom were on stable treatment for at least three months with cholinesterase inhibitors Aricept (donepezil), Exelon (rivastigmine), or Razadyne (galantamine).
The participants were randomly assigned to receive montelukast film — 10mg per day or 30mg twice-daily doses — or a placebo, together with cholinesterase inhibitors, for 26 weeks, or about six months. After this period, patient cognition was assessed through a battery of neuropsychological tests.
A total of 52 patients completed the 26 weeks, according to Intelgenx.
When considering all treatment doses together, the results revealed no general cognition benefits compared with the placebo, the company noted. However, when analyzing each dose separately, patients who received at least 80% of the 30 mg twice-daily doses of montelukast had a statistically significant cognitive improvement.
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