Monopar Therapeutics presented promising long-term data for its Wilson disease drug candidate ALXN1840 (tiomolybdate choline) at the European Association for the Study of the Liver (EASL) International Liver Congress 2025 in Amsterdam. The late-breaker presentation highlighted sustained efficacy and favorable safety outcomes over a median treatment period exceeding 2.5 years.
Wilson disease is a rare genetic disorder where the body's mechanism for removing excess copper is impaired, resulting in toxic copper accumulation in tissues and organs, particularly the liver and brain. Current standard-of-care treatments have limitations in efficacy and tolerability, creating a significant unmet need for improved therapeutic options.
Comprehensive Clinical Data Analysis
The presented data pooled results from three clinical trials: Phase 2 WTX101-201, Phase 2 ALXN1840-WD-205, and Phase 3 WTX101-301, encompassing 255 patients for efficacy analysis. Safety data included an additional Phase 2 trial (ALXN1840-WD-204), bringing the total to 266 patients. The median treatment duration was 961 days (2.63 years) for efficacy assessment and 943.5 days (2.58 years) for safety evaluation.
Dr. Karl Heinz Weiss, Medical Director of Salem Medical Center Heidelberg and lead author of the presentation, emphasized the significance of the findings: "These data show that the long-term efficacy, safety, and convenience profile of ALXN1840 are very encouraging and that ALXN1840 has the potential to provide a meaningful benefit to Wilson disease patients' daily lives."
Key Efficacy Outcomes
The analysis revealed multiple positive outcomes for patients treated with ALXN1840:
- Sustained improvements from baseline in the Unified Wilson Disease Rating Scale (UWDRS) Part II (patient-reported symptoms) and Part III (clinician-assessed symptoms)
- Increased copper mobilization evidenced by sustained elevation in directly measured non-ceruloplasmin-bound copper (dNCC)
- Superior improvements on the Clinical Global Impression – Improvement (CGI-I) scale compared to standard of care
- Improvement in the New Wilson Index, which incorporates key laboratory parameters including bilirubin, AST, INR, leukocytes, and albumin
Notably, patients reported higher convenience and effectiveness with ALXN1840 compared to standard-of-care treatments. This advantage was also observed in patients who transitioned from standard therapy to ALXN1840 during the extension phase of the Phase 3 trial.
Safety Profile
The safety analysis yielded encouraging results, with fewer than 5% of patients experiencing drug-related serious adverse events (SAEs). Importantly, no cases of drug-related renal or urinary system SAEs were reported, addressing a significant concern with some existing Wilson disease treatments.
Clinical Significance
Wilson disease affects approximately 1 in 30,000 people worldwide. Without proper treatment, the condition can lead to severe liver damage, neurological problems, and psychiatric symptoms. Current treatments include chelating agents like penicillamine and trientine, which help remove copper from the body, and zinc salts that reduce copper absorption. However, these treatments can be associated with significant side effects and compliance challenges.
ALXN1840's mechanism as a copper-protein binding agent (tiomolybdate choline) offers a different approach to managing copper levels. The sustained improvements observed across multiple clinical parameters suggest potential advantages over existing therapies.
Future Directions
Monopar Therapeutics, a clinical-stage biopharmaceutical company focused on developing treatments for patients with unmet medical needs, continues to advance ALXN1840 through its development program. The company's pipeline also includes radiopharmaceutical programs for cancer imaging and treatment.
The selection of these data for a late-breaker presentation at EASL 2025, one of the most prestigious liver disease conferences globally, underscores the potential significance of ALXN1840 in addressing the therapeutic challenges of Wilson disease. Late-breaker abstracts at EASL undergo rigorous review, with selection criteria including significance, potential impact, and the presentation of recent, up-to-date research findings.
As regulatory discussions progress, the Wilson disease community will be watching closely to see if ALXN1840 can translate these promising clinical results into a new treatment option that addresses the limitations of current therapies and improves quality of life for patients living with this challenging condition.
