A novel method of Alzheimer's disease drug absorption

In the Age of Covid, news on research has been really, really slow.  When I see something interesting I try to write about it, but it's been slow.  According to ALZForum, the most important thing about last year was the Aduhelm controversy.  But maybe things are perking up.

The company IntelGenx has just resumed the Phase 2a clinical trial of the repurposed asthma drug montelukast for mild to moderate Alzheimer’s disease, although it has some challenging side effects.  The trial was interrupted by covid.  It was approved in 1998 to treat asthma, but it appears to have anti-inflammatory characteristics and can help in the formation of new neurons.  

And the drug has been re-tooled with some new technology.  When it is inhaled or ingested it goes straight from the intestines to the liver and can get lost.  IntelGenx has a new film technology that promotes absorption in the mouth directly into the blood stream.  This bypasses the liver and allows it to travel unimpeded to the brain.

"Montelukast VersaFilm" may have advantages over ingested medication, including an easier method of administration. It's an oral film that allows for increased concentration at the affected site because it bypasses the body’s initial treatment of swallowed medications in the liver.

The phase 1 trial found that VersaFilm administration was safe and tolerated by healthy subjects.  It had 52% higher bioavailability than other forms of administration (pills or inhaled), and it easily crosses the blood-brain barrier.  (We discussed the blood-brain barrier in Beating the Dementia Monster.)  But did it work?  That remains to be seen.  If it worked really well in the phase 1 trial I believe that we'd have heard more about it.

For the current trial, patients will receive the drug once or twice daily for 26 weeks.  After 26 weeks, they will receive a battery of neuropsychological tests.  I'd guess the tests will be similar to the tests I've been getting almost annually since 2015.

It will be a while before we know anything, but if the re-tooled montelukast does anything at all to improve memory and cognition, it can rival Aduhelm.  Semiannual MRIs won't be required, and it will be a lot cheaper.  Montelukast is already generic, although we will need to spend more on the VersaFilm technology.  But I doubt it will be the $28,000 per year that Biogen wants for Aduhelm. All factors considered, it may not need to do much to challenge Aduhelm.

You can read more here.