Axcella Shifts Focus to Long COVID, NASH Amid Leadership Losses


As Axcella grapples with the abrupt resignation of R&D chief Alison D. Schecter and board member Shreeram Aradhye, the company is prioritizing its clinical development portfolio to focus on its investigative assets for COVID-19 and non-alcoholic steatohepatitis (NASH), while suspending a mid-stage rare disease study.

In a filing with the U.S. Securities and Exchange Commission earlier this week, Axcella announced the departure of Schecter, president of research and development, as well as Aradhye. Schecter joined Axcella on March 2, 2021 and is leaving the company to pursue other opportunities, Axcella said in its filing. Aradhye also left for personal reasons. Axcella said his departure “was not the result of a disagreement with the company on any matter relating to the company’s operations, policies or practices.”

Regarding its pipeline, Axcella said it is suspending its Phase II study in Overt Hepatic Encephalopathy that is assessing the efficacy and safety of AXA1665, an experimental oral candidate for the reduction in risk of recurrent forms of the disease. OHE is a common central nervous system disorder caused by chronic liver diseases that affect the brain and brain function. The liver is unable to clear toxin buildup from the body. Those toxins can travel to the brain and can cause confusion and other symptoms. The treatment is reversible.  The only current drug approved for this indication is Salix Pharmaceuticals’ Xifaxan.

Enrollment in the Axcella OHE trial began last year. Although the company noted investigator interest in this potential treatment for the rare disease, Axcella noted that “enrollment challenges and timelines to approval” are likely to be longer than expected and warranted a suspension of the program to focus on other developmental assets.

“We continue to believe that AXA1665 is an effective therapy based upon two prior clinical trials, physician input, and AXA1665’s strong scientific support. We will explore partnerships and potentially other indications for AXA1665,” Bill Hinshaw, president and chief executive officer of Axcella said in a statement.

Two years ago, AXA1665 posted positive topline data from a study that saw clinically-relevant trends in certain measures of nitrogen/ammonia handling and physical function, the company said at the time.

With the study of AXA1665 suspended, the company will aim its resources at its Long COVID and NASH studies. In Long COVID, Axcella is assessing AXA1125 in a Phase IIa study. This morning, the company noted that enrollment in the study is complete with 40 patients and topline data is expected in the third quarter of this year. AXA1125 is a multi-targeted endogenous metabolic modulator (EMM) composition that contains five amino acids and an amino acid derivative that works across multiple biological pathways. The company noted that preclinical and clinical data have shown that AXA1125 has the potential to increase fatty acid oxidation, ATP production, ketogenesis and mitochondrial bioenergetics, which can contribute to meaningful reductions in key markets of liver fat, insulin resistance, inflammation, and fibrosis. 

Hinshaw said the execution of the Phase IIa Long COVID trial will advance the company’s pipeline and validate the effectiveness of EMMs to address multi-factorial diseases.

“Achieving completion of enrollment is a significant milestone in the development path of AXA1125 as a potential treatment for Long COVID, a large and growing consequence of the global pandemic,” Margaret Koziel, chief medical officer of Axcella said in a statement. “We believe mitochondrial dysfunction is a key driver of Long COVID induced fatigue. Preclinical and clinical data indicate that AXA1125 may have an important impact.”

AXA1125 is also being assessed in a Phase IIb study as a potential treatment for NASH, a condition in which excess fat is stored in the liver and is not caused by heavy alcohol use. There are no approved therapies for NASH other than lifestyle adjustments. Axcella expects data from the Phase IIb study in the third quarter of this year.

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