Yaqrit's Liver Drug Rides Wave of Shifting HE Treatment Paradigm

LONDON, UK – April 17, 2026 – A perfect storm is brewing in the world of advanced liver disease, and London-based Yaqrit finds itself at its center. The company's novel treatments for hepatic encephalopathy (HE) are poised to gain significant traction following the concurrent publication of three pivotal papers that reshape the clinical landscape. The developments include new Phase 2a data showing their oral drug, YAQ007, effectively reduces ammonia, a new global consensus validating ammonia as a key disease marker, and mounting pressure to limit the use of a standard-of-care antibiotic due to resistance concerns.

These converging events reinforce the strategic direction of Yaqrit, a late clinical-stage company, as it prepares to launch late-stage trials for its ammonia-scavenging drugs, YAQ006 and YAQ007. For the hundreds of thousands of patients hospitalized each year with HE—a debilitating neurological complication of liver disease—this shift could herald a new era of more targeted and effective therapies.

The Ammonia Consensus: A Watershed Moment in Diagnosis

For years, the role of ammonia in hepatic encephalopathy has been a subject of clinical debate. While understood to be a key toxin accumulating in patients with failing livers, its variability and measurement challenges led to inconsistent diagnostic guidelines. That ambiguity has now been swept aside by a landmark consensus paper in the Journal of Hepatology.

Spearheaded by the International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN), the paper establishes a clear global consensus among leading liver specialists. Through a rigorous Delphi process, over 90% of the expert panel agreed on the use of blood ammonia levels as a crucial diagnostic and prognostic tool in liver disease. The recommendations provide specific guidance on when and how to measure ammonia, aiming to standardize clinical practice and research worldwide.

This represents a significant paradigm shift. While some regional guidelines, like those from the European Association for the Study of the Liver (EASL), had already begun recommending ammonia measurement, others, including older guidance from the American Association for the Study of Liver Diseases (AASLD), had been more cautious, citing concerns over correlation with HE severity. The new ISHEN consensus provides the harmonized, evidence-based framework that the field has been waiting for.

“Progress in advanced liver disease has to be contingent on generating evidence that moves consensus thinking beyond standard hypotheses,” said Rajiv Jalan, Founder and CMO of Yaqrit and an author on all three of the recent papers. “As specialist liver disease physicians turn routinely to measurements of blood ammonia as a diagnostic and prognostic marker, the importance of treatments such YAQ007 and YAQ006 that reduce ammonia directly may become more apparent.”

A Standard Treatment Faces New Headwinds

The new focus on ammonia as a primary target comes at a time when a cornerstone of current HE therapy, the antibiotic rifaximin, is facing increased scrutiny. While clinically proven to help prevent recurrent episodes of HE, its broader role and long-term safety are being questioned.

A sharply worded "viewpoint" article in The Lancet Gastroenterology & Hepatology highlights a growing dilemma for clinicians. The authors argue that recent large-scale trials have challenged the idea that rifaximin is a broad, disease-modifying therapy. More alarmingly, they point to emerging evidence of a significant risk: antimicrobial resistance (AMR).

This is not a theoretical concern. A recent multi-national study provided real-world evidence linking rifaximin use to a more than two-fold increased risk of developing resistance to other critical antibiotics, including vancomycin. This challenges the long-held belief that rifaximin, a non-absorbable antibiotic, is a low-risk intervention. The authors of the Lancet piece advocate for placing rifaximin under global antimicrobial stewardship frameworks, restricting its use to narrower, proven indications to preserve its effectiveness and limit the spread of resistance. This creates a pressing need for effective, non-antibiotic alternatives for managing HE.

Yaqrit's Ammonia Scavengers Enter the Spotlight

Into this evolving landscape steps Yaqrit with its pipeline of L-ornithine phenylacetate (OPA) formulations. Unlike rifaximin, which works by altering gut bacteria, Yaqrit's drugs are ammonia scavengers that work directly to remove the toxic compound from the bloodstream.

The timing of their latest data release could not be better. A study published in the journal Hepatology details the results of a Phase 2a trial for YAQ007, the company's oral OPA formulation. The data clearly shows that treatment with YAQ007 leads to a direct reduction in blood ammonia levels in patients with cirrhosis and HE. A related dose-setting study further revealed that a 4g twice-daily dose of YAQ007 produced a six-fold greater decrease in plasma ammonia compared to the standard dose of rifaximin, with a comparable safety profile.

This clinical proof-of-concept, demonstrating a direct impact on the newly validated target of ammonia, provides strong support for Yaqrit's upcoming trials. The company is preparing to launch a Phase 2b/3 trial later this year to test YAQ007 in preventing the recurrence of HE.

Simultaneously, its intravenous formulation, YAQ006, is being advanced for the treatment of acute HE episodes. A Phase 3 trial is also slated to begin this year. YAQ006 has already received Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration (FDA), signaling its potential to address a significant unmet medical need. The FDA has also approved the use of a novel assessment tool, the Modified Hepatic Encephalopathy Staging Tool (mHEST), as the primary endpoint for this trial, smoothing its regulatory path forward.

Navigating a Crowded but Needy Market

Hepatic encephalopathy places a staggering burden on patients and healthcare systems. Up to 40% of patients with decompensated cirrhosis are at risk, contributing to approximately 200,000 hospitalizations in the United States alone each year. With recurrence rates as high as 50% within a year of an initial episode, the need for better therapies is acute.

The global HE market, valued at over $1.8 billion, is projected to continue its steady growth, driven by the rising prevalence of chronic liver disease. While current first-line treatments like lactulose and rifaximin are mainstays, they are not without drawbacks. Lactulose is often poorly tolerated, and as discussed, rifaximin faces the looming threat of AMR. The field is ripe for innovation, with other companies exploring gut microbiota modulation and other novel mechanisms.

Yaqrit's strategy, however, seems uniquely aligned with the current clinical moment. By focusing on a direct, non-antibiotic mechanism to lower ammonia, their therapies offer a potential solution to the key limitations of existing standards of care.

“Unmet needs in conditions like HE are evolving not only with the aging population but also with increasing precision surrounding the effectiveness of conventionally-used drugs,” said Troels Jordansen, Chief Executive Officer of Yaqrit. “Patients who already have few treatments options need therapies that go beyond the limitations of conventional remedies.”

As Yaqrit prepares to move its promising OPA formulations into pivotal late-stage trials, the entire hepatology community will be watching closely. The convergence of a new diagnostic consensus, challenges to an old standby, and promising data for a novel mechanism has set the stage for a potential transformation in how this devastating complication of liver disease is managed.