Breakthrough Multi-Targeted Drug Candidates Puts Axcella at Forefront of Liver Disease Treatment Market

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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Liver diseases like cirrhosis and nonalcoholic steatohepatitis (NASH) are deadly and afflict millions of Americans with debilitating mental and physical symptoms that become progressively worse each year. Axcella Health Inc. AXLA, a clinical-stage biotech company focused on developing enhanced treatments for underserved complex diseases, has made exciting progress in the development of two potential treatments for liver-related conditions. Despite the severity and prevalence of these conditions, there has so far been a lack of available drugs that comprehensively treat them. Axcella hopes to change that with its pipeline of drug candidates that use amino acids and their derivatives to target multiple factors that drive complex and hard to treat conditions like NASH and overt hepatic encephalopathy, which is a severe cognitive impairment caused by cirrhosis. 

Unlocking the Potential of Endogenous Metabolic Modulators for Liver-Related Conditions

Many diseases stem from the dysregulation of a single pathway or gene within the body. Others are multifactorial — meaning they have multiple causes — which has historically made them difficult to develop treatments for, especially treatments that can comprehensively address the multiple complications that come with them. 

Because of these challenges, some conditions, like nonalcoholic steatohepatitis (NASH), have no approved treatments at all, while others, like overt hepatic encephalopathy (OHE), have treatments that target just one of the drivers of the disease, leaving other complications unaddressed. 

Axcella develops compositions of endogenous metabolic modulators (EMMs) that can simultaneously and safely target multiple metabolic pathways. As a result, these unique EMM compositions have the potential to address a broader range of underlying causes and symptoms. 

Axcella’s AXA1125 for NASH

One of these EMM combinations is AXA1125, Axcella’s drug candidate for the treatment of nonalcoholic steatohepatitis (NASH). NASH is a progressive disease in which the liver cannot properly break down fatty acids and carbohydrates. This leads to a buildup of liver fat and insulin resistance which causes inflammation, cell death and fibrosis. 

If left untreated, NASH can continue to worsen and can lead to cirrhosis, liver failure, heart failure, liver cancer and death.

AXA1125 combines six amino acids and derivatives that, together, have demonstrated the potential to increase insulin sensitivity, reduce inflammation and promote glucose uptake. By targeting these various metabolic processes, the drug candidate is showing the potential to prevent liver fat buildup and insulin resistance while simultaneously targeting drivers of liver inflammation and fibrosis (liver scarring).

With nearly 870 million patients worldwide that are estimated to have NASH and expectations that this population will continue growing rapidly, analysts expect the market for effective treatments of the progressive disease to reach $13 billion by 2030. Axcella’s AXA1125, currently in a Phase 2b clinical trial, is poised to be a first-of-its-kind treatment in this large but underserved market.

Axcella’s AXA1665 for Overt Hepatic Encephalopathy

Another exciting drug candidate in Axcella’s pipeline is AXA1665, an EMM composition in development to treat overt hepatic encephalopathy (OHE). OHE is a common complication of cirrhosis that stems from the liver’s inability to filter out toxins from the blood. As a result, these toxins build up and cross the blood-brain barrier, causing OHE. Patients with OHE suffer from confusion, severe personality changes, inappropriate behavior, hand tremors, sleepiness and other mental and physical problems.

Although two treatments for OHE have been approved, they focus only on reducing ammonia levels in the body, which helps with the mental symptoms and reduces the risk of hospitalization and mortality. However, there is still an urgent need for a drug that can offer more significant and consistent long-term improvements in the health and symptoms of patients with OHE. 

That’s why Axcella is advancing AXA1665, which combines eight amino acids and derivatives to target three factors involved in OHE: ammonia toxicity, amino acid imbalance and muscle wasting. The EMM combination aims to restore the liver’s ability to break down and eliminate ammonia, promote muscle protein synthesis, and support the metabolic pathways involved in maintaining the balance of amino acids. 

What that could mean for patients is fewer mental and physical symptoms, fewer hospitalizations, and an overall improved quality of life.

The global market for OHE treatments is already estimated to be approximately $1 billion, and if approved, a treatment like AXA1665 has the potential to increase this market size by more comprehensively meeting the needs of patients with this condition.

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.