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Yahoo
23-05-2025
- Health
- Yahoo
Together for Better Liver Health: WHA78 Side Event Unites Global Stakeholders to Strengthen Public Health Responses to Metabolic Disease
Geneva, Switzerland, May 23, 2025 (GLOBE NEWSWIRE) -- Global health leaders call for urgent, integrated action on the rising rates of metabolic liver disease during a high-level policy event held on the sidelines of the 78th World Health Assembly and co-hosted by Global Liver Institute (GLI), the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD). This event brought together leading experts, policymakers, public health officials, and advocates to push for stronger public health strategies that address liver disease as part of the global noncommunicable diseases (NCDs) response and highlight the need to embed liver health within national NCD strategies. 'With liver disease now being the fourth leading cause of adult death in Mexico, we are acting early—starting from pregnancy to school-age—with education, screening, and healthier environments. Our vision is prevention-driven and science-led', shared Marta Zapata-Tarres, MD, PhD, Sub Secretary for Health and Director for National Institutes of Health, Mexico. During the event, GLI released the second edition of the Best Practices in Liver Health Policy report, featuring 5 new case studies from Brazil, Japan, Mexico, Spain, and Qatar to demonstrate the integration of liver health into clinical pathways and broader health frameworks. Mohamed Hassany, MD, Prof., Minister's Assistant for Projects and Public Health Initiatives, Ministry of Health and Population, The Arab Republic of Egypt mentioned, 'The Hepatitis C campaign taught us a vital lesson: data-driven national efforts combined with trained human resources and specialized centers can change the course of a public health crisis. We now have the opportunity to apply these same tools to address severe liver disease.' Speakers championed a comprehensive, cross-sectoral approach to liver health, including early diagnosis and treatment, community-based care models, and policy frameworks aligned with Universal Health Coverage and the WHO Global NCDs Action Plan. 'To overcome barriers like fragmented data and limited access, we are building a smarter, more connected system. By integrating data and partnering with the private sector, we are creating a future where liver health is no longer neglected,' shares Mary Ann Palermo-Maestrai, Undersecretary, Department of Health, Philippines. As momentum builds toward the 4th United Nations High-Level Meeting (UNHLM) on NCDs in September 2025, GLI will continue to drive global policy action and strengthen international collaboration to secure liver health as a core global health priority. CONTACT: Christine Maalouf Global Liver Institute cmaalouf@ in to access your portfolio
Yahoo
17-05-2025
- Health
- Yahoo
2025 EASL Congress Spotlight: CG-0416 Preclinical Data Unveils A Groundbreaking Dual-Action Therapy Targeting Obesity and MASH
——A First-in-Class Hydrolysis-Activated Liver-Targeted THR-β Prodrug Demonstrating A Dual Advantage of Fat Reduction and Muscle Preservation SHANGHAI, May 16, 2025 /PRNewswire/ -- At the European Association for the Study of the Liver (EASL) Annual Congress, CureGene Pharmaceuticals ("CureGene") announced late-breaking preclinical results for its investigational liver-targeted thyroid hormone receptor beta (THR-β) prodrug, CG-0416. Presented in a Late-Breaking Poster session, the data highlight triple therapeutic potential of CG-0416 in metabolic dysfunction-associated steatohepatitis (MASH) and weight management: including 58% reduction in hepatic lipid accumulation; 66% improvement in weight loss efficacy; and 50% lower muscle loss rate compared to standard therapies. These findings position CG-0416 as a novel dual-mechanism candidate for concurrent MASH and obesity management. Addressing Current Therapeutic Limitations While GLP-1 receptor agonists (e.g., semaglutide, tirzepatide) face challenges in sustained weight control and muscle preservation, CG-0416 employs precision targeting of complementary metabolic pathways to overcome these limitations. Key Innovations 1. Enhanced Safety Profile CG-0416's liver-specific activation achieves intrahepatic active metabolite concentrations 20-fold higher than in peripheral tissues, minimizing systemic THR-β activation and improving long-term safety. 2. Muscle Preservation Breakthrough In 26-week diet-induced obesity (DIO) murine models, CG-0416 combined with low-dose semaglutide demonstrated: 66% greater fat mass reduction (vs. semaglutide monotherapy) Muscle-to-fat loss ratio of 0.18 kg/kg (vs. 0.35-0.63 kg/kg in existing therapies) Advantages for Clinical Translation 1. Dual-Pathway Synergy CG-0416 enhances GLP-1-mediated hepatic lipid oxidation while activating the IGF-1/Akt/FOXO3a axis to suppress muscle catabolism. 2. Oral Administration Potential With 92% oral bioavailability – doubling that of approved THR-β therapies – CG-0416 may enable the first oral combination regimen with GLP-1 agonists. CG-0416's EASL debut garnered significant attention for its rigorous preclinical validation and innovative design. The compound's ability to reprogram metabolic pathways while maintaining safety underscores its potential to redefine standards in metabolic disease treatment. About CG-0416 CG-0416 is a novel liver-targeted THR-β prodrug in development for MASH & obesity-related complications. Its tissue-selective activation mechanism simultaneously addresses hepatic lipid accumulation, inflammation, and fibrosis, while demonstrating superior metabolic control to resmetirom and VK-2809 in preclinical studies. As a potential oral adjunct to GLP-1 therapies, CG-0416 combines rapid fat reduction with muscle preservation, positioning it as a next-generation metabolic modulator. For comprehensive information on CG-0416 and the latest updates, please visit CureGene's official website at About CureGene Established in 2018, CureGene is China-based, globally oriented biotech company with research and development offices in both China and the United States. The company has developed innovative platforms rooted in core expertise and capabilities, focusing on cardio-cerebrovascular and antiviral disease areas. CureGene has advanced pipelines of novel drugs with significant market potential and fully owned global intellectual property rights. The company, guided by its mission, has attracted a team of distinguished scientists with extensive global pharmaceutical experience. Through a strategic vision, CureGene has transitioned successfully from a research-stage startup into a clinical-stage biotech company, with all pipelines demonstrating First-in-Class or Best-in-Class potential. Forward-Looking Statement The information released in this press release may contain certain forward-looking statements (such as "will", "anticipate", "forecast", "expect", "intend", "plan", "believe", "estimate", "be confident" and other similar expressions), which are based on the current views, beliefs and expectations that the Company or its management has towards the Company's business operations and financial performance when such statements are made. These forward-looking statements shall not be deemed as guarantees of future outcomes, and such outcomes may be affected by risks, uncertainties, and other factors, some of which are beyond the Company's control and difficult to predict. Therefore, subject to the impacts of our business, general industry conditions and competition, environment, politics, general economic factors (including fluctuations in interest rates and exchange rates), pharmaceutical industry regulations and medical policies, technological developments, new products and patents obtained by any competitors, the inherent challenges in new product development (including obtaining regulatory approvals), production difficulties or delays, instability in the international economic and financial situation and sovereign risks, reliance on the effectiveness of the protection of the Company's patents and other innovative products, the Company's risks of facing patent litigation and/or regulatory actions, future changes and developments in social situations and other various factors and assumptions, the actual results may differ significantly from the information contained in the forward-looking statements. Such forward-looking statements shall not in any way be considered as any commitments/guarantee made by the Company, its subsidiaries, or any of its directors, officers, management personnel, advisors, employees and/or agents regarding relevant matters. They do not constitute a recommendation to engage in a certain act. None of such personnel assumes any liability with respect to such forward-looking statements. Moreover, the Company and its subsidiaries, directors, management personnel, consultants, employees and/or agents have not and will not assume any responsibility for updating the forward-looking statements contained in this press release to reflect the latest information, future projects or circumstances or events that occur after the release date. View original content: SOURCE CureGene Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Yahoo
12-05-2025
- Business
- Yahoo
Atea Pharmaceuticals Reports First Quarter 2025 Financial Results and Provides Business Update
Enrollment Ongoing in Phase 3 C-BEYOND Trial for Treatment of HCV Full Phase 2 Results for Regimen of Bemnifosbuvir and Ruzasvir for HCV and Results from Three Additional Phase 1 Studies Supporting Potential Best-in-Class Profile Presented at European Association for the Study of the Liver (EASL) Congress 2025 Virtual Investor Event with Key Opinion Leader Insights on HCV to be Held May 14, 2025, at 10:00 AM ET BOSTON, May 12, 2025 (GLOBE NEWSWIRE) -- Atea Pharmaceuticals, Inc. (Nasdaq: AVIR) (Atea or Company), a clinical-stage biopharmaceutical company engaged in the discovery and development of oral antiviral therapeutics for serious viral diseases, today reported financial results for the first quarter ended March 31, 2025 and provided a business update. The Company's combination regimen of bemnifosbuvir (BEM), a nucleotide analog polymerase inhibitor, and ruzasvir (RZR), an NS5A inhibitor, is in Phase 3 development for the treatment of hepatitis C virus (HCV). 'Atea has made very significant progress thus far in 2025, initiating and continuing to enroll patients in C-BEYOND, our Phase 3 clinical trial evaluating the regimen of bemnifosbuvir and ruzasvir for the treatment of HCV in the US and Canada,' said Jean-Pierre Sommadossi, PhD, Chief Executive Officer and Founder of Atea. 'We are also focused on initiating our second Phase 3 trial, C-FORWARD, which will be conducted at clinical sites outside of North America. We expect enrollment of patients in C-FORWARD to begin mid-year.' "We are very encouraged by the positive results of the Phase 2 clinical study and additional data presented at EASL 2025 supporting the efficacy, safety and potential best-in-class profile of our regimen of bemnifosbuvir and ruzasvir, including short treatment duration, low risk for drug-drug interactions, and convenience with no food effect,' continued Dr. Sommadossi. 'We believe our regimen, if approved, has the potential to increase the number of treated and cured HCV patients and to disrupt the global HCV market of approximately $3 billion in net sales." HCV KOL Investor Event to be Held May 14, 2025 at 10:00 AM ET Atea will host a virtual key opinion leader (KOL) investor event with a panel of HCV experts and prescribers on Wednesday, May 14, 2025, at 10:00 AM ET. To register, click here. This KOL event will replace Atea's first quarter 2025 earnings conference call, and Quarterly calls will resume with the second quarter 2025 financial results. This investor event will include an expert panel of several leaders in hepatology, gastroenterology, infectious diseases, and HCV treatments in the US, Canada and Europe. These experts and prescribers will discuss the current challenges experienced by people living with HCV, the full results of Atea's global Phase 2 study evaluating the regimen of BEM/RZR for the treatment of HCV, and what a new optimized HCV therapy could provide for prescribers and patients. Company management will discuss the HCV commercial market opportunity and the ongoing global Phase 3 clinical development. Summary of Results Presented at EASL Poster Title: Efficacy and Safety of Bemnifosbuvir and Ruzasvir after 8 Weeks of Treatment in Patients with Chronic Hepatitis C Virus (HCV) Infection (TOP-251)Conclusion: The Phase 2 study results demonstrated that an 8-week combination regimen of BEM (550 mg) and RZR (180 mg) achieved SVR12 in 98% of treatment-adherent patients and 95% of patients regardless of treatment adherence. The regimen was safe and well-tolerated with low rates of virologic failure and no study-drug-related serious adverse events or treatment discontinuations. Treatment emergent adverse events (TEAEs) were reported in 43% (118/275) of patients. Most TEAEs were mild to moderate in intensity, with headache (9%) and nausea (8%) being the most reported. These results reinforce the potential of the combination regimen of BEM and RZR as a best-in-class treatment for Title: Pharmacokinetics of Bemnifosbuvir in Participants with Hepatic Impairment (WED-278)Conclusion: A Phase 1 pharmacokinetic study evaluating a single 550 mg dose of BEM in participants with varying degrees of hepatic impairment showed increased drug exposure in individuals with moderate to severe liver dysfunction. However, these changes did not meaningfully affect levels of AT-273, the plasma marker for the active intracellular antiviral metabolite of BEM. No safety concerns were identified. These results support the use of BEM without dose adjustment in patients with hepatic impairment. Poster Title: No DDI Between Bemnifosbuvir/Ruzasvir and Bictegravir/Emtricitabine/Tenofovir Alafenamide (WED-279)Conclusion: Findings from a Phase 1 drug-drug interaction study in healthy participants demonstrated that co-administration of BEM/RZR with the standard human immunodeficiency virus (HIV) regimen bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF) resulted in no clinically significant pharmacokinetic changes. The co-administered HCV/HIV combinations were generally safe and well tolerated. These results support the future inclusion of HCV/HIV co-infected patients receiving these HIV therapies in the Phase 3 clinical development program for BEM/RZR. It is estimated that in the US as many as 6 to 30% of HCV patients are co-infected with HIV.1 Poster Title: Pharmacokinetics of Bemnifosbuvir in Participants with Renal Impairment (WED-280)Conclusion: A Phase 1 renal impairment study showed that a single 550 mg dose of BEM was safe and well-tolerated across participants with normal kidney function, moderate-to-severe renal impairment, and those with end-stage renal disease on hemodialysis. While the circulating inactive nucleoside metabolites of BEM increased as expected in renally impaired individuals, exposure of BEM remained consistent. These findings suggest that BEM may be used without dose adjustment in patients with renal dysfunction, including those undergoing dialysis. About the Bemnifosbuvir / Ruzasvir HCV Phase 3 Program Atea's HCV Phase 3 program includes two open-label Phase 3 trials, C-BEYOND in the US and Canada, and C-FORWARD, a global trial outside of North America. Each Phase 3 trial will enroll approximately 880 treatment-naïve patients, including those with and without compensated cirrhosis. The trials will compare the fixed-dose combination (FDC) regimen of BEM/RZR to the FDC regimen of sofosbuvir and velpatasvir. The regimen of BEM/RZR will be administered orally once-daily for eight weeks (in patients without cirrhosis) or 12 weeks (in patients with compensated cirrhosis) while the regimen of sofosbuvir and velpatasvir will be administered orally once-daily for 12 weeks to all patients, with or without compensated cirrhosis. The primary endpoint for each trial is HCV RNA < lower limit of quantitation (LLOQ) at 24 weeks from the start of treatment and encompasses sustained virologic response 12 weeks post-treatment (SVR12) in each arm. Measurement at 24 weeks from the start of treatment is to ensure the primary endpoint occurs at the same relative timepoint from the start of treatment in all patients. Patient enrollment in the C-BEYOND trial is ongoing and enrollment in the C-FORWARD trial is expected to begin in mid-2025. The initiation of the Phase 3 program follows a successful engagement with the US Food and Drug Administration (FDA) at an End-of-Phase 2 meeting in January 2025, shortly after the Company announced the topline results from the Phase 2 study evaluating the potential best-in-class regimen of BEM/RZR, including data demonstrating that the regimen met its primary endpoints of efficacy (SVR12) and safety. Business and Organizational Updates In December 2024, Atea engaged Evercore, a global independent investment bank, to identify potential opportunities to enhance shareholder value. The process includes a review of a broad range of strategic alternatives, including strategic partnerships, acquisition, merger, or other business combination, sale of assets or other strategic transactions. The process is ongoing, and the Company continues to evaluate all options to maximize shareholder value. In the first quarter 2025, to enhance efficiency in the management of infrastructure expenditures, Atea reduced its workforce by approximately 25%. This workforce reduction is expected to result in cost savings of approximately $15 million through 2027. In February 2025, Arthur S. Kirsch was appointed to the Company's Board of Directors. Mr. Kirsch has extensive knowledge of the healthcare and life sciences industries gained from decades of investment banking and capital markets experience as well as extensive public board and strategic experience. In April 2025, Atea further refreshed its Board of Directors with the appointment of Howard H. Berman, PhD. The appointment of Dr. Berman, who is currently serving as an observer, will become effective upon the completion of Atea's 2025 Annual Meeting of Stockholders. Dr. Berman has over 20 years of entrepreneurial and life science industry experience working at the interplay of science and business. In April 2025, Atea announced that its Board had authorized the repurchase of up to $25 million of the Company's common stock. This authorization reflects the Company's commitment to return capital to shareholders, while maintaining the capacity to complete its global Phase 3 HCV program and position Atea for long-term success. First Quarter 2025 Financial Results Cash, Cash Equivalents and Marketable Securities: $425.4 million at March 31, 2025, compared to $454.7 million at December 31, 2024. Research and Development Expenses: Research and development expenses decreased by $28.0 million from $57.6 million for the three months ended March 31, 2024, to $29.6 million for the three months ended March 31, 2025. The net decrease was primarily driven by lower external spend as Atea's COVID-19 Phase 3 SUNRISE-3 clinical trial was completed in 2024. The decrease was offset by an increase in external spend principally related to startup activities for the Company's HCV Phase 3 clinical development. Additionally, a decrease in internal research and development expenses was primarily related to lower stock-based compensation expense in the three-month period ended March 31, 2025. General and Administrative Expenses: General and administrative expenses decreased by $2.8 million from $12.2 million for the three months ended March 31, 2024, to $9.5 million for the three months ended March 31, 2025. The net decrease was primarily related to lower stock-based compensation expense, partially offset by increased professional Income and Other, Net: Interest income and other, net, decreased by $1.9 million for the three months ended March 31, 2025, compared to the three months ended March 31, 2024, primarily due to lower investment balances. Income Taxes: Income tax expense was $0.2 million for the three months ended March 31, 2025, and March 31, 2024. Condensed Consolidated Statement of Operations and Comprehensive Loss(in thousands, except share and per share amounts)(unaudited) Three Months EndedMarch 31, 2025 2024 Operating expenses Research and development $ 29,584 $ 57,575 General and administrative 9,457 12,231 Total operating expenses 39,041 69,806 Loss from operations (39,041 ) (69,806 ) Interest income and other, net 4,972 6,868 Loss before income taxes (34,069 ) (62,938 ) Income tax expense (203 ) (231 ) Net loss $ (34,272 ) $ (63,169 ) Other comprehensive loss Unrealized loss on available-for-sale investments (115 ) (388 ) Comprehensive loss $ (34,387 ) $ (63,557 ) Net loss per share - basic and diluted $ (0.40 ) $ (0.75 ) Weighted-average number of common shares - basic and diluted 85,159,254 83,916,193 Selected Condensed Consolidated Balance Sheet Data(in thousands)(unaudited) March 31, 2025 December 31, 2024 Cash, cash equivalents and marketable securities $ 425,436 $ 454,721 Working capital(1) 411,961 443,752 Total assets 439,964 464,668 Total liabilities 28,880 25,801 Total stockholder's equity 411,084 438,867 (1 ) Atea defines working capital as current assets less current liabilities. See the Company's condensed consolidated financial statements in its Quarterly Report on Form 10-Q for the three months ended March 31, 2025, for further detail regarding its current assets and liabilities. About HCV HCV is a blood-borne, positive-sense, single-stranded (ss) RNA virus that primarily infects liver cells. HCV is a leading cause of chronic liver disease and liver transplants, spreading via blood transfusion, hemodialysis and needle sticks, with approximately 240,000 deaths occurring each year. Despite the availability of direct-acting antivirals, HCV continues to be a significant global healthcare issue. An estimated 50 million people worldwide are chronically infected with HCV and there are approximately one million new infections each year. In the US, between 2.4 and 4 million people are estimated to have HCV with annual new infections outpacing treatment rates. HCV infections in the US predominate in patients in the age group between 20-49 years old, and it is estimated that less than 10% of HCV-infected patients in the US have cirrhosis. Chronic HCV infection is the leading cause of liver cancer in the US, Europe and Japan. About Atea Pharmaceuticals Atea is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing oral antiviral therapies to address the unmet medical needs of patients with serious viral infections. Leveraging Atea's deep understanding of antiviral drug development, nucleos(t)ide chemistry, biology, biochemistry and virology, Atea has built a proprietary nucleos(t)ide prodrug platform to develop novel product candidates to treat single stranded ribonucleic acid, or ssRNA, viruses, which are a prevalent cause of serious viral diseases. Atea plans to continue to build its pipeline of antiviral product candidates by augmenting its nucleos(t)ide platform with other classes of antivirals that may be used in combination with its nucleos(t)ide product candidates. Atea's lead program and current focus is on the development of the combination of bemnifosbuvir, a nucleotide analog polymerase inhibitor, and ruzasvir, an NS5A inhibitor, to treat HCV. For more information, please visit Forward-Looking Statements This press release includes 'forward-looking statements' within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include but are not limited to statements regarding the potential best-in-class profile of the regimen of BEM and RZR for the treatment of HCV, the potential opportunity created by the regimen to increase the number of patients treated and cured, the opportunity to disrupt the global HCV market, the expected time of commencement of enrollment in the C-FORWARD Phase 3 clinical trial, future results of operations and financial position, business strategy, anticipated milestone events and timelines for clinical trials, benefits of cost savings initiatives, repurchases under the Company's share repurchase program, the timing and outcome of the Company's strategic alternatives review, the timing and agenda of the Company's KOL event and the Company's plans to resume Quarterly earnings calls in the second quarter of 2025. When used herein, words including 'expected,' 'should,' 'anticipated,' 'believe.' 'will,' 'plans', and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon Atea's current expectations and various assumptions. Atea believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Atea may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, uncertainties inherent in the drug discovery and development process and the regulatory submission or approval process, unexpected or unfavorable safety or efficacy data or results observed during clinical trials or in data readouts; delays in or disruptions to clinical trials or our business; our reliance on third parties over which we may not always have full control, our ability to manufacture sufficient commercial product, competition from approved treatments for HCV, the timeline for the completion of the strategic alternatives review process is unknown and there can be no assurance that the process will result in any particular outcome; dependence on the success of Atea's most advanced product candidates, in particular the combination of BEM and RZR for the treatment of HCV; as well as the other important factors discussed under the caption 'Risk Factors' in Atea's Quarterly Report on Form 10-Q for the quarter ended March 31, 2025 as such factors may be updated from time to time in its other filings with the SEC, which are accessible on the SEC's website at These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While Atea may elect to update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing Atea's views as of any date subsequent to the date of this press release. Contacts Jonae BarnesSVP, Investor Relations and Corporate Joyce AllaireLifeSci Advisorsjallaire@ 1
Medscape
12-05-2025
- Health
- Medscape
Drug Slows Progression of Primary Sclerosing Cholangitis
AMSTERDAM — Norucholic acid (NCA), an investigational therapy, demonstrated significant superiority over placebo in halting disease progression in patients with primary sclerosing cholangitis (PSC), meeting the primary efficacy endpoint in a phase 3 trial presented on May 10 at the European Association for the Study of the Liver (EASL) Congress 2025. NCA was four times more effective in partially normalizing the liver enzyme alkaline phosphatase (ALP) (odds ratio [OR], 4.16), without worsening of the histologic Ludwig stage of PSC. Results held true with and without concomitant ursodeoxycholic acid (UDCA). Michael Trauner, MD The interim 96-week efficacy and safety results were presented by Michael Trauner, MD, professor of gastroenterology and hepatology at the Medical University of Vienna, Austria, who first developed the compound two decades ago. 'In this study, NCA hit the primary and key secondary endpoint in this clinical trial that included liver histology and biochemical features,' said Trauner. 'There were higher response rates for NCA than placebo both with and without concomitant UDCA, as well as improvement and less worsening of histological disease stages with NCA compared with placebo.' First Data to Offer Hope for Reducing PSC Progression PSC is a rare, progressive cholangiopathy characterized by inflammation and fibrosis of the bile ducts, with no current medical therapy proven to alter its course. NCA works by inducing bicarbonate-rich hypercholeresis and promoting cholangiocyte protection, with additional anti-inflammatory and immunomodulatory effects. The multicenter, international, randomized, placebo-controlled, double-blind phase 3 study builds on earlier phase 2 findings in which NCA improved cholestasis markers in a dose-dependent manner and was well tolerated. Patients (n = 301) were randomized in a 2:1 ratio to receive either NCA 1500 mg once daily (n = 205) or placebo (n = 96), stratified by concomitant UDCA use. Biopsies were done 4-8 weeks prior to randomization and again at week 96 and will be repeated at week 192. The study remains ongoing, with 2 additional years of blinded treatment planned. The combined primary endpoint was defined as partial normalization of ALP to less than 1.5 times the upper limit of normal and no worsening of Ludwig histologic stage. Secondary endpoints included modified Nakanuma staging, liver stiffness measurement (FibroScan), enhanced liver fibrosis and Amsterdam-Oxford scores, patient-reported pruritus and fatigue, and overall quality of life. 'The population was typical of PSC, with men in their 40s making up 74% of participants, and around 70% had inflammatory bowel disease,' reported Trauner. Baseline ALP was approximately 300 U/L, and liver stiffness and enhanced liver fibrosis scores were around 10. Most patients presented with Ludwig stage 2 or 3 disease. Statistically Significant Benefit Compared With Placebo By week 96, 27.3% of patients in the NCA group and 37.5% in the placebo group had discontinued the trial. In the intention-to-treat analysis, the combined primary endpoint was achieved by 15.1% of patients in the NCA group vs 4.2% in the placebo group, a difference of 10.96% (95% CI, 4.6%-17.3%) and an OR of 4.16 (95% CI, 1.42-12.22; P = .0048). Patients without a second biopsy were considered nonresponders. In the per-protocol analysis, which included only participants who completed both biopsies, the benefit remained significant: 18.2% for NCA vs 6.6% for placebo, with a difference of 11.7% (95% CI, 3.0%-20.3%) and an OR of 3.36 (95% CI, 1.12-10.11; P = .0155). The key secondary endpoint of ALP less than 1.5 times the upper limit of normal and no worsening according to modified Nakanuma staging was also met. NCA again outperformed placebo: 15.1% vs 5.2%, a difference of 9.9% (95% CI, 3.3%-16.5%). Consistent Efficacy, With or Without UDCA Trauner noted that NCA demonstrated greater efficacy than placebo in both subgroups, with and without concomitant UDCA. The treatment difference with UDCA was 7.5% (95% CI, 0.4%-14.7%), whereas without UDCA, the difference increased to 23.4% (95% CI, 11.3%-35.5%). 'Those not receiving UDCA had a much higher response rate at 23% with NCA,' he said. Histologic and Biochemical Improvements; Safety Good Histologic improvement by at least one Ludwig stage occurred in 25.2% of patients in the NCA group compared with 10.5% in the placebo group ( P = .0217). Notably, progression to cirrhosis (Ludwig stage 4) occurred less frequently in the NCA group (5.9% vs 10.7%). Significant improvements were also seen in liver enzymes, including ALP, alanine aminotransferase, and gamma-glutamyltransferase, with greater reductions in the NCA group at week 96. The Amsterdam-Oxford prognostic score increased significantly more in the placebo group, indicating greater disease progression. NCA was generally well tolerated, with a safety profile comparable to that of placebo. Treatment-emergent adverse events occurred in 97.6% of the NCA group and 92.7% of the placebo group. The most common adverse events included diarrhea, SARS-CoV-2 infection, and nasopharyngitis. Expert: 'Desperate Need for Treatment' Ahmed Elsharkawy, MD, consultant hepatologist at University Hospitals Birmingham NHS Foundation Trust, United Kingdom, who co-moderated the session, underscored the importance of these findings. 'There is a desperate need for patients with PSC to have access to treatments that slow down the progression of their condition, as we currently do not have any available drugs to treat them,' he explained. Reflecting on the study's impact, he added, 'This study provides the first-ever data that offers some hope that norucholic acid can help reduce progression of the disease for some but unfortunately not yet all patients with the condition. This is hopefully the first step towards developing a cure for this devastating condition that disproportionately affects young individuals.'
Medscape
12-05-2025
- Health
- Medscape
AI in Liver Care Needs Vigilance and Tailoring to Population
AMSTERDAM — As artificial intelligence (AI) becomes increasingly embedded within healthcare, including liver care, it will be essential to tailor AI to the local population and ensure regular model monitoring to ensure both effective and safe outcomes for patients. Ashley Spann, MD, is a transplant hepatologist interested in developing informatics and AI to optimize outcomes in liver disease, including transplantation, at Vanderbilt University Medical Center, Nashville, Tennessee. At European Association for the Study of the Liver (EASL) Congress 2025, she shared advice on ethics and how to implement AI into the liver clinic in a session on the impact of AI on the hepatology practice. Ashley Spann, MD 'We need to include patients and providers from the very beginning, not build in silos. The data must be representative of the population of concern, the technical solution must fit the clinical problem, and the model must not cause harm,' Spann told Medscape Medical News in an interview after her talk. She stressed that principles of clinical care, particularly non-maleficence, also have a place in the use of AI. 'AI is already around us. The question is: Should we use it? And if so, how do we do it responsibly?' To this end, Spann discussed best practices for model development, clinical implementation, and a key safeguard she termed algorithmovigilance : The ongoing monitoring of AI models after deployment to detect performance drift and prevent harm. 'We can minimize harm by setting parameters for the model so we know when the performance starts to lag in real time and patients might be affected. If this happens, we turn the model off, reassess, retrain, and redeploy.' 'Each step of the way, from inception to deployment, we must track what the model is doing and ensure it isn't making care worse for patients,' she said. Buy or Build — Key Questions for Adoption Spann stressed the importance of starting with the clinical problem and then layering in appropriate AI technology while always considering the protection of patients. Whether building or buying a model, ensuring that it reflects the population of concern is paramount. Most AI models are trained on historical healthcare data. This means that it could reflect systemic inequalities, such as risk factor prevalences among a specific population, underdiagnosis, undertreatment, or lack of access to care among marginalized populations. In this case, the model learns and replicates those patterns. 'We must make sure biases and disparities don't worsen,' she said. 'If a model begins to underperform, we need to know when and how to intervene.' Spann urged clinicians and institutions to interrogate the data available when deciding which model is appropriate. For example, when building a model, she suggested asking whether some patient groups in your dataset are more affected than others. If buying a model, she suggested asking whether the model addressed the clinical problem in need of solving. For instance, AI might be a solution for identifying people with undetected cirrhosis within a population-level approach to the problem. 'It's crucial to ask what data are available that could be useful to make that prediction and are there patients who are disproportionately affected? There might be certain patients without available data even though they may have a disease, and what are the implications of that?' She cited an example from her institution, where the Fibrosis-4 (FIB-4) Index was integrated into the electronic health records to automate liver fibrosis risk stratification. More than half the patients lacked the key lab values needed to generate a FIB-4 score. 'They might still have disease, but without those labs, we can't know the risk severity. The question becomes, what are the data that we need and how do we get it? That's a data gap with real implications,' Spann explained. Mismatched Populations Can Render a Model Useless When buying an AI model, Spann cautioned against applying them to populations too different from those on which it was trained. She cited a model that was developed using data from the US Veterans Affairs system, which mostly contains patients who are older White men and, as such, may not generalize well to urban centers serving more diverse populations. 'That population is a very unique subset of patients. The only way to determine the suitability or not is to take that model and test it retrospectively and look at how the model might change and then locally track performance over time.' She also underscored how sociodemographic and economic factors such as proximity to transplant centers or to a liver clinic can skew outcomes, and these are most likely not accounted for in a model's clinical inputs. 'We need to consider how well a model performs in those subgroups because it may be erroneous in them.' AI's Role in Population Health Session co-moderator, Tom Luedde, MD, director at Heinrich Heine University Düsseldorf in Düsseldorf, Germany, considered the impact promised by AI for liver care. 'Prevention, detection, risk prediction, and actually getting patients into the healthcare system are our biggest deficits in liver disease. AI could help fill those gaps,' he said. 'Right now, general practices are not implementing FIB-4 in daily practice, for example, but we might get there with an LLM [large language model] or an AI system that provides patients with access to the hepatology system. I believe, with these approaches, we will have a greater impact than with any single drug or complex intervention. In the future, I can envisage AI being implemented in a type of health kiosk. And with all the resource issues we have, this might help.'
