New Alzheimer's Disease Drug Candidate with Dual Mode of Action May Show Decreased Side Effects in Clinical Trials

The following post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga.

The clinical stage biopharmaceutical company, Alpha Cognition ((TSX.V: ACOG, OTC:ACOGF), is initiating a pivotal relative bioavailability study of ALPHA-1062, a proprietary, delayed release oral tablet formulation of a prodrug of galantamine. This trial, if successful, will allow the company to submit an NDA for ALPHA-1062 in 2022.  ALPHA-1062 is being developed as a new generation acetylcholinesterase inhibitor (AChEI) designed to improve upon the existing standard of care therapies by accelerating treatment effect, improving treatment limiting gastrointestinal side effects and delaying progression of Alzheimer's Disease (AD).

During the company’s R&D day webcast, researchers reported exciting preliminary results demonstrating that the unique dual mode of action of Alpha 1062 could have significant benefits in patients with AD. Here’s why that dual mode of action is so important and what makes Alpha 1062 such an exciting entry into the AD treatment space.

Alpha 1062’s Dual Mode of Action

In patients with Alzheimer’s disease, neurotransmitters like acetylcholine are found to be in low levels of supply in the brain. These lower levels lead to poor memory, learning difficulties and other cognitive deficits. To address this, physicians have long relied on acetylcholinesterase inhibitors (AChEIs).  These treatments have shown to be effective at treating the symptoms of AD and have been the standard of care for over a decade.

Alpha 1062, similarly increases acetylcholine levels in the brain. But it also works by  modulating the alpha-7 nicotinic acetylcholine receptor (nAChR), another neurotransmitter that’s also been shown to play an important role in memory and attention. By acting on both of these neurotransmitters, ALPHA-1062 can potentially provide benefits for patients suffering from cognitive decline associated with AD.

Research confirms that this dual mode of action boosts the positive results of the treatment. In a long-term study published in “Neurology,” patients taking an AChEI had a 27% lower risk of death and continued to perform better on cognitive tests compared to untreated patients. For those in the study who were taking galantamine (the active ingredient in ALPHA-1062), the decreased risk of death was 29%. These patients also performed the best on their annual cognitive tests and were less likely to develop severe dementia. 

In another long-term study published in the “International Journal of Geriatric Psychiatry,” patients taking galantamine were 80% more likely to be living independently during the follow-up 3 years later than untreated patients. For each year patients took galantamine, they reduced risk of needing 24 hour care 31% vs. patients taking no therapy.  Those in the study who took other AChEIs had similar but marginally lower chances of living independently. 

The Benefits of Galantamine Without the Drawbacks

With Galantamine’s positive results, it seems surprising that it hasn’t become more widely used among patients with AD. The reason for this is due to the negative side effects associated with the drug — particularly the gastrointestinal distress like diarrhea and vomiting that can make adhering to the treatment extremely difficult. 

To unlock the benefits of galantamine without the side effects, the research team at Alpha Cognition developed Alpha 1062 as a compound of the potent (but side effect-heavy) galantamine. By adding a benzoyl ester, the drug blocks binding with the AChE in the gastrointestinal nervous system.  As a result, Alpha 1062 has no effect in the gastrointestinal system because it passes through inertly, or with no active drug effect.  In contrast, other oral AChEI medications often overstimulate local neurons and trigger intense GI side effects. 

ALPHA-1062 is then metabolized by the liver and active drug is carried to the brain via the circulatory system. The formulation also increases the bioavailability of the galantamine so that patients are getting the benefits of the drug.  

If approved, the patented treatment could become the first of its kind to offer the improvements in cognitive function and overall quality of life promised by galantamine without the debilitating side effects that have made it difficult for patients to adhere to for extended periods of time. 

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The preceding post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga. Although the piece is not and should not be construed as editorial content, the sponsored content team works to ensure that any and all information contained within is true and accurate to the best of their knowledge and research. This content is for informational purposes only and not intended to be investing advice.