Axcella's Leading Drug Candidate for Overt Hepatic Encephalopathy Offers Hope in a Market Requiring Innovation

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.

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The clinical-stage biotech company Axcella AXLA uses endogenous metabolic modulators (EMMs) to treat complex diseases, including liver conditions. One of its leading drug candidates, AXA1665, relies on a pioneering composition of amino acids to offer more comprehensive relief to patients suffering from progressively worsening effects resulting from cirrhosis.

AXA1665 has recently entered a new Phase 2 clinical trial, and here’s why it could revolutionize the treatment landscape for overt hepatic encephalopathy (OHE).

Existing OHE Treatments Offer Limited Relief

There are estimated to be approximately 500,000 people who suffer from hepatic encephalopathy (HE) in the United States alone and 150,000 new cases are diagnosed each year. As a result, it’s already become a $1 billion market, even as drug development in the space has largely stalled in recent years.

HE is a debilitating condition caused by a cascade of events. Given the damaged state of the liver, this organ is unable to perform its normal function of processing and clearing toxins from the body. Toxins like ammonia build up in the blood and eventually reach the brain. This then leads to cognitive impairment and a range of behavioral problems like jumbled speech, shaking hands, confusion, disorientation, and extreme fatigue. Muscles try to help in the detoxification process, but they do it poorly and end up wasting away in the process (an associated condition known as sarcopenia). 

At first, these neurocognitive symptoms may be hard to detect, which is a condition known as minimal hepatic encephalopathy (MHE). In contrast, patients with OHE are easily identifiable and often are impaired to the point where they are unable to care for themselves.

Only two medications are being regularly used to treat OHE: lactulose and rifaximin. Both of these products focus on only one of the drivers of the condition, namely ammonia. The most widely used agent is lactulose, which is a syrup that works like a laxative. This product is dosed multiple times a day in order to rid the body of ammonia via frequent bowel movements. Given the manner in which this product works, tolerability and compliance are common issues for patients, their caregivers, and physicians.

Rifaximin is a broad-spectrum antibiotic that helps to reduce the growth of ammonia-producing bacteria in the body. However, it is only approved for use in the U.S. when combined with lactulose. Additionally, similar to lactulose, rifaximin does not address the muscle wasting that often accompanies OHE.

Both of these products have been on the market for well over 15 years and, given their limitations and drawbacks, innovation would be welcomed by patients and the medical community.

AXA1665 Aims to Offer Better Results With Fewer Side Effects

Currently in a Phase 2 clinical trial, AXA1665 is Axcella’s answer to a market in desperate need of a drug that does more than just lower ammonia levels. The multitargeted oral drug candidate is a compound of 8 amino acids that target three biological processes in the body. 

First, it seeks to increase ammonia metabolism by promoting the urea cycle — the process by which ammonia is converted into urea, which is then expelled from the body through urination. AXA1665 then aims to increase branch chain amino acids and reduce aromatic amino acids, which may contribute to OHE events. Additionally, this drug candidate seeks to allow patients to maintain their muscle mass and enhance their muscle function. In the end, targeting each of these processes is expected to improve neurocognition, reduce the number of OHE events that patients experience, and allow patients to improve their quality of life.

The latest published research on AXA1665 included 60 patients with cirrhosis and found that the drug showed meaningful improvements in the participants taking it. After just 12 weeks, participants taking AXA1665 showed significant improvement in measures of cognitive and physical function compared to the placebo group. 

The next clinical trial is already underway and will examine AXA1665’s ability to improve cognition, reduce OHE events and improve physical function among other measures over a longer 24-week period and across a larger group of 150 patients. 

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.