Can Resverlogix's Apabetalone Succeed Where Biogen's Aducanumab Failed?

Disclosure Right Up Front

I don't like burying disclosure statements at the bottom of a post, especially when I'm long.  

I am a shareholder in Resverlogix which trades in Canada with the symbol RVX.TO or in the US (RVXCF) and hold what for me represents a very significant position, in fact its my single largest holding. As such anything I write should be viewed as having bias and consequently this blog posting should be viewed as being for entertainment purposes only.

While I endeavor to ensure that any data and information posted is factual I make no guarantees to that effect and recommend that readers verify any and all information posted.

I am not a registered investment advisor and stocks comport significant risk. Engagement of a professional is strongly advised before making any investment.

What happened with Aducanumab?

It was believed that Aducanumab, by reducing amyloid plaques, would prove an effective treatment for Alzheimer's disease.  Aducanumab was infused into the bloodstream once a month.

The decision to halt the ENGAGE and EMERGE trials was made by an Independent Data Monitoring Committee after reaching the determination that the trials were not likely to meet their primary objective.

For a more detailed explanation of Biogen's (BIIB) trials and the development of Aducanumab I'll invite readers to check out the following link:

Aducanumab - Alzheimer's News Today

While Aducanumab may have failed as a treatment for Alzheimer's there could yet be an application for this drug.  I am certain Biogen will pour over all the data from their failed trials to see if there is potential for other indications.  

How is Apabetalone different from Aducanumab?

The Mechanism of Action for Aducanumab was shown to be penetration of the brain, targetting tight fibrils and soluble oligomers of amyloid.  As noted earlier the drug was infused into the bloodstream. Apabetlone's MOA by contrast is described as Epigenetic and is administered orally in capsule form.

Followers of Biotech have no doubt come across the term Epigenetics.  In a nutshell its the level above the genes, Epi being Latin for above.  Rather than altering genes it involves what has been described as a switch, turning genes from a diseased state to a healthy state by means of transcription.

Resverlogix's Apabetalone is a compound that is currently in a Phase 3 events based trial that is projected to be wrapping up sometime in the next few weeks.  Because of something called the 'Complement Cascade' it is believed that Apabetalone may have the potential to impact a myriad of conditions, one of which is Alzheimer's.  

For those with a more scientific background I will invite you to watch this four minute long video put out by Resverlogix in 2016 that goes into much greater deatil. 

BETonMACE Phase 3 Trial of Apabetalone

BETonMACE is a Phase 3 trial that has been running since October of 2015 and is projected to wrap up sometime in April with top-line results expected sometime around mid year (June 30th 2019).  

While the primary outcome is not related to Alzheimer's there is a subset of patients aged 70 years and higher who are undergoing the Montreal Cognitive Assessment (MoCA) at various stages during the trial to determine whether or not Apabetalone has the potential to impact cognitive impairment which can result from conditions like Alzheimer's and Vascular Dementia.  

Here is a news release speaking directly to this subgroup of patients.

Resverlogix Presents at Clinical Trials in Alzheimer's Disease (CTAD) Asia 2018

As mentioned in that PR, of the approximately 2,400 patients enrolled in the trial about 450 are aged 70 years and older.  Further about half of those 450 older patients had MoCA scores below 25 which is indicative of mild cognitive impairment.  

Do note that while that PR from Sept 2018 had the trial projected to finish around the end of 2018, that date has now been moved forward to April as mentioned previously.  

As with Biogen's ENGAGE and EMERGE trials Resverlogix's BETonMACE trial has periodic reviews that are conducted by an Independent Data Safety Monitoring Board.  There have been eight reviews so far and all have reccomended that the trial continue without modification.  The reviews have taken place at roughly four month intervals with the last one being announced back in December of 2018.  Here is a link to that announcement:

https://www.globenewswire.com/news-release/2018/12/19/1669505/0/en/Resverlogix-Announces-Eighth-Positive-Data-Safety-Monitoring-Board-Recommendation-For-Phase-3-Study-of-Apabetalone.html

What happens if those dosed with Apabetalone show improved MoCA scores?

The primary end point of the BETonMACE trial is not Alzheimer's or Vascular Dementia.  The primary end point is about measuring the time to first occurrence of a Major Adverse Cardiac Event, (MACE for short) in patients with Diabetes Mellitus. 

All patients in the trial are insulin dependent diabetics who have suffered a recent acute coronary syndrome event, (within 90 days) as well as having low HDL levels.  In simple terms this patient population is at very high risk of MACE.

Resverlogix is hoping to prove that Apabetalone in tandem with Standard of Care (Soc) will show a statistically significant Relative Risk Reduction versus placebo with SoC.

If the sub analysis of patients over the age of 70 demonstrates positive benefits in regards to MoCA scores, then I fully expect there would be further clinical trials designed with a goal of measuring cognition.  

Summary

As with many of my blog posts I like to stress that Seeking Alpha should obviously never be the end of someone's research and due diligence.  If this is your first introduction to Resverlogix and Apabetalone I will provide some links, and I welcome any commentary or questions below.  

Currently there is no US listing for the company's shares, so those without access to Canada's big board TSX who trade over U.S. exchanges must use the OTC platform where the company's ticker symbol is RVXCF.  The company has engaged Paris based Rothschild & Co in efforts to secure a U.S. listing however nothing as yet has come of that.  

Here is a chart showing the performance of RVXCF for the past year.  

Here is the link to the trial information at clinicaltrials.gov

Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD - Full Text View - ClinicalTrials.gov

Here's a link to an article on Apabetalone from The Journal of The Alzheimer's Association:

https://www.alzheimersanddementia.com/article/S1552-5260(18)30893-8/abstract

This is a link to a company slide on Apabetalone:

Apabetalone - Resverlogix Corp.

And a final link with a poster about Neurodegenerative disease from a CTAD conference in Barcelona back in October of 2018:

https://www.resverlogix.com/upload/media_element/144/aa9c9bf7caa6/ctad-europe-poster-2018.pdf

Again, comments are always welcome.