Will Anavex for “Autisms” be worth the wait and the price, compared to Russian OTC Afobazole?

US-Russia cooperation has long been possible in Space, but not so often in Medicine. NASA reportedly pays Russia $85 million per astronaut to go the International Space Station (ISS).  The US Space Shuttle program ended in 2011, leaving a Russian Soyuz rocket the only way to the ISS.

This post comes ahead of the dietary autism post, awaited by Tanya.  It really is just a brief follow-on from the previous post. I have only just come across Anavex, which does add weight to the first post on sigma-1R.
                                                                                                               

Hundreds of millions of dollars are being spent in the US to develop a safe sigma-1R agonist (Anavex 2-73). This drug is being trialed in various autisms (Rett, Fragile X and Angelman syndromes), Parkinson’s and Alzheimer’s.

In the last post I wrote about a cheap OTC anxiety drug from Russia, called Afobazole, that appears to be a safe sigma-1R agonist.  This drug has also recently been trialed in autism and Parkinson’s - the same targets as Anavex.

I did make the point in my original sigma-1 post that I am interested in existing therapies, rather than potential ones, so I did not include Anavex, or any other research drug, in that post. Anavex is nonetheless interesting, because their research studies further support the suggestion that targeting ER stress via sigma-1 is an interesting avenue to pursue.  

ERStress and Protein Misfolding in Autism (and IP3R again) and perhaps what to do about it - Activation of Sigma-1 Chaperone Activity by Afobazole?

Anavex is claiming precision medicine, but in fact sigma-1R agonists appear more like the opposite, at least in terms of who you target.  The majority of both common and rare neurological disorders look like they should benefit from reducing ER Stress (from whatever cause); it is a shared feature.  So it looks more like a shotgun approach; that is actually a good thing, if it were to drive the price down.

What is needed is an affordable, effective, mass market drug; not an ultra expensive pill just for Rett Syndrome and perhaps a different colour version for Angelman's Syndrome.

Which will prove effective - Anavex or Afobazole? Or perhaps neither.

Having already made the case for Soyuz in my earlier post, here is the case for NASA, and for those with NASA-sized budgets, courtesy of  https://www.anavex.com/

Animal Study Details Motor, Sensory and Respiratory Benefits of Anavex 2-73, Supporting Phase 2 Trials

Treatment with Anavex 2-73 was seen to improve motor skills, acoustic responses and visual acuity in a mouse model of Rett syndrome, supporting ongoing Phase 2 studies in patients.

Its use also helped to lessen abnormal movements and ease breathing in these mice, its researchers said.

The study, “ANAVEX®2-73 (blarcamesine), a Sigma-1 receptor agonist, ameliorates neurologic impairments in a mouse model of Rett syndrome,” was published in the journal Pharmacology Biochemistry and Behavior.

Anavex 2-73 (blarcamesine) is an oral investigational therapy developed by Anavex Life Sciences that works by activating the sigma-1 receptor (S1R), a protein involved in the correct folding of other proteins.

S1R activation results in reduced toxic accumulation of misfolded proteins, as well as lesser dysfunction in mitochondria (a cell’s “powerhouse”), oxidative stress and neuroinflammation, all involved in Rett syndrome. (Oxidative stress is an imbalance between the production of free radicals — potentially harmful molecules associated with a number of diseases — and the generation of antioxidant defenses.)

Researchers at Anavex, assisted by PsychoGenics, evaluated the potential treatment’s specific effects on Rett symptoms in a validated mouse model.

They assessed motor function (balance, motor coordination, locomotion, and abnormal movements or stereotypies), sensory function (reflex responses to sound stimuli and visual clarity), and respiratory function.

Motor and sensory functions were assessed in younger mice, while visual acuity and breathing were measured in older animals.

Results showed that Anavex 2-73 significantly eased motor dysfunction, and deficits in acoustic and visual responses compared to mice given a placebo.

Anavex 2-73 also induced a significant reduction in two distinctive features of Rett syndrome found in these mice: hind-limb clasping (an abnormal posture comparable to hand stereotypies in people with Rett), and apnea (involuntary breath-holding) that is the most concerning breathing abnormality in Rett syndrome, the researchers said. These improvements were mainly dependent on treatment dose and duration.

“In conclusion, the data demonstrate that [Anavex 2-73] is effective in ameliorating multiple neurobehavioral phenotypes in [Rett] mice,” the researchers wrote. “In line with previous animal and human studies [in other neurodegenerative diseases], [Anavex 2-73] also showed a good safety profile,” they added.

These data served as a proof-of-concept for an ongoing safety and efficacy Phase 2 trial called RS-001 (NCT03758924, still enrolling) in the U.S., and for the Phase 2 AVATAR study (NCT03941444) in Australia. These trials together will evaluate Anavex 2-73 in up to 51 women with Rett syndrome.

Conclusion

It may be that Anavex is far superior to the cheap Afobazole. Like the space shuttle was far more advanced than the Soyuz. 

But what if the cheap Afobazole is quite good enough?  Like the cramped, but reliable Soyuz rocket.

Anavex/Afobazole will not cure any severe neurological condition, just improve it, so it will need to be part of a polytherapy. That means the patient will need to be able to afford multiple drugs, somehow.

Coming back to those autisms, what if your daughter has Rett Syndrome, or son has Fragile-X Syndrome ?  Wait a few years for Anavex and for someone else to pay for it? or make do with some cheap Afobazole?