Axcella Announces Initiation of EMMPACTSM Phase 2b Clinical Trial of AXA1125

Rhea-AI Summary

Axcella (Nasdaq: AXLA) has activated clinical sites and initiated patient screening for its EMMPACT Phase 2b clinical trial of AXA1125, targeting NASH treatment. The trial will enroll about 270 patients, assessing the efficacy and safety of AXA1125 over 48 weeks. Primary endpoint focuses on histological improvements in NAFLD Activity Score, with secondary endpoints including fibrosis resolution. Axcella's CEO noted the trial's commencement as a significant milestone after clearing its IND application.

NASH affects up to 40 million in the U.S., with no approved treatments available.

Positive

• Initiation of EMMPACT Phase 2b clinical trial for AXA1125, indicating progress in NASH treatment development.
• Trial designed to evaluate efficacy in a significant patient population (270 patients) with multiple endpoints.
• AXA1125 has shown promising results in previous studies, indicating potential for meaningful clinical benefits.

Negative

• No approved drug therapies for NASH currently available in the U.S.
• Potential competition exists in an expanding market as NASH incidence increases with obesity and diabetes trends.

Axcella (Nasdaq: AXLA), a clinical-stage biotechnology company pioneering a new approach to treat complex diseases and improve health using endogenous metabolic modulator (EMM) compositions, today announced that it has activated initial clinical sites and begun patient screening for its EMMPACT Phase 2b clinical trial of AXA1125, the company’s multi-targeted oral product candidate for the treatment of NASH.

“NASH is the quintessential complex disease, involving the dysregulation of numerous biological pathways and impacting an enormous, heterogenous global population,” said Stephen A. Harrison, M.D., Medical Director of Pinnacle Clinical Research in San Antonio, TX, visiting professor of Hepatology at the University of Oxford, UK and the principal investigator of EMMPACT. “These factors have confounded many physicians and drug developers in the past. Given its multi-modal mechanism, the activity and tolerability seen in past clinical studies and the presumed safety of its underlying amino acids, AXA1125 holds the potential to serve as an ideal first-line NASH agent. We are excited to have EMMPACT underway and are eager to gauge AXA1125’s histological impact.”

Axcella has branded this global trial EMMPACT based on the potential for AXA1125, an EMM composition, to deliver meaningful, multifactorial clinical benefits to patients with NASH. This randomized, double-blind, placebo-controlled, multi-center investigation will evaluate the efficacy and safety of AXA1125 in patients with biopsy-confirmed F2/F3 NASH. Approximately 270 patients will be enrolled and randomized 1:1:1 to receive either 45.2 or 67.8 grams per day of AXA1125 or a matched placebo in two divided doses for 48 weeks, with a four-week safety follow-up period. Patients will be stratified based on the presence or absence of type 2 diabetes.

“The initiation of EMMPACT is the latest in a series of exciting recent milestones for Axcella and comes just one month after clearing our IND application for AXA1125, which is a testament to our team’s strong preparation and execution as well as our investigators’ interest and engagement,” said Bill Hinshaw, President and Chief Executive Officer of Axcella. “I am confident in our ability to extend our successful track record and rapidly enroll this clinical trial.”

EMMPACT will be conducted globally across more than 70 clinical sites with a primary endpoint assessing the proportion of patients with a biopsy-confirmed ≥2 point improvement in NAFLD Activity Score (NAS) after the 48-week treatment period. Secondary endpoints will include the proportion of patients achieving biopsy-confirmed resolution of NASH without worsening of fibrosis and the proportion of patients achieving a ≥1 stage improvement in fibrosis without worsening of NASH. A range of non-invasive biomarkers, including MRI-PDFF and Fibroscan, will be utilized for additional endpoints and an interim analysis in the trial.

“In two consecutive clinical studies of AXA1125 in subjects with presumed NASH, meaningful improvements were seen in non-invasive measures of hepatic fat, insulin resistance, inflammation and fibrosis,” said Alison Schecter, M.D., President of R&D at Axcella. “We expect EMMPACT to provide robust insights on AXA1125’s dose response, longer-term effects, histological impact and potential differentiation in type 2 diabetics that can be leveraged to expand our development efforts.”

Additional trial information can be found on https://clinicaltrials.gov/ via the identifier NCT04880187.

About AXA1125 and Nonalcoholic Steatohepatitis (NASH)

NASH is the most severe form of fatty liver disease and is driven by multifactorial systemic dysregulation of pathways associated with metabolism, inflammation and fibrosis. If left untreated, this disease may ultimately lead to life-threatening conditions such as cirrhosis or liver cancer, requiring liver transplant. According to the Global Liver Institute’s U.S. NASH Action Plan published in December 2020, up to 40 million people in the U.S. alone are living with NASH and approximately 10% of U.S. children are afflicted with this disease. Incidence is expected to continue increasing in parallel with the obesity and type 2 diabetes epidemics. Currently, there are no approved drug therapies for NASH in the United States.

AXA1125, Axcella’s product candidate for treatment of NASH, is a composition of six amino acids and derivatives that is designed to target multiple metabolic pathways known to affect the pathogenesis of fatty liver disease. In prior clinical studies, this oral product candidate has been safe, well tolerated and has demonstrated the potential to reduce liver fat, inflammation and fibrosis with a safe and well tolerated profile while avoiding an impact on lipids and weight. AXA1125 is now in Phase 2b development.

About Endogenous Metabolic Modulators (EMMs)

EMMs are a broad family of naturally occurring molecules, including amino acids, that regulate human metabolism. Axcella is developing a range of novel product candidates that are comprised of multiple EMMs engineered in distinct combinations and ratios to simultaneously impact multiple metabolic pathways to modify the underlying causes of various complex diseases and improve health.

About Axcella’s Clinical Studies

Each of the clinical investigations that the company has completed to date have been conducted as non-investigational new drug application (IND) clinical studies under U.S. Food and Drug Administration regulations and guidance supporting research with food. These studies evaluate product candidates for safety, tolerability and effects on the normal stru

FAQ

What is the purpose of Axcella's EMMPACT trial for AXA1125?

The EMMPACT trial aims to evaluate the efficacy and safety of AXA1125 in treating NASH.

When did Axcella initiate the EMMPACT clinical trial for AXA1125?

Axcella began patient screening for the EMMPACT trial recently, following the clearance of their IND application.

What are the primary endpoints of the EMMPACT trial for AXA1125?

The primary endpoint is assessing the proportion of patients with a biopsy-confirmed ≥2 point improvement in NAFLD Activity Score after 48 weeks.

How many patients will be enrolled in the EMMPACT trial for AXA1125?

The trial plans to enroll approximately 270 patients.

What is the current status of NASH treatment options in the U.S.?

There are currently no approved drug therapies for NASH in the United States.