2024-11-03-艾昆纬-MASH临床研究见解-GLP-1激动剂的可及性增加（英）_13页_647kb

Summary of White Paper: Insights into MASH Clinical Research

Core Content

This white paper explores the challenges faced in enrolling patients for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH) clinical trials, particularly in the United States, and provides insights into how these challenges may evolve globally. The focus is on the impact of increased access to Glucagon-Like Peptide-1 (GLP-1) agonists and their effect on patient eligibility and recruitment for MASH trials.

Main Points

1. MASH and MASLD Overview

• MASLD and MASH are significant public health concerns, with MASH being a major cause of liver fibrosis and cirrhosis.
• MASLD affects ~32.4% of the global population, and MASH affects 3–5%.
• In the U.S., ~100 million people are estimated to have MASLD, with ~20% having MASH (or ~5% of U.S. adults).
• Currently, only one FDA-approved therapy for MASH exists: resmetirom (Rezdiffra™).

2. Enrollment Trends in U.S. MASH Trials

• There has been a sharp decline in enrollment rates for Phase IIb and III MASH trials in the U.S.
• Median enrollment rate dropped from 0.41 patients per site per month (2012–15) to 0.07 patients per site per month (2020–23), a 83% decrease.
• This decline is attributed to increased access to GLP-1 agonists and GIPs combined with GLP-1s, which are effective in treating T2DM and obesity, key risk factors for MASH.
• GLP-1 sales in the U.S. increased by 1,265% from Q4 2015 to Q4 2023, driven by new drug approvals such as semaglutide (Ozempic®) and tirzepatide (Mounjaro®).
• The recent FDA approval of semaglutide for cardiovascular risk reduction in overweight or obese patients has further expanded access to GLP-1s.

3. Implications for Future Enrollment

• The pool of potential patients for MASH trials is expected to continue declining in the U.S. due to:
  • Reduced interest in trial participation if patients have access to GLP-1s.
  • Ineligibility if patients are on unstable doses of GLP-1s.
  • Patient preference for trials involving GLP-1s in T2DM and obesity that do not require liver biopsies.
• Similar trends are anticipated in other countries as GLP-1s become more accessible.
• Sponsors should diversify their strategies and evaluate enrollment potential in less traditional, less competitive countries.

4. GLP-1 Saturation Index

• IQVIA has developed a GLP-1 saturation index to compare country-level utilization, calculated as total GLP-1 sales divided by the adult population.
• Sample data from five countries shows:
  • United States: 0.91
  • Poland: 0.36
  • United Kingdom: 0.33
  • Brazil: 0.10
  • South Korea: 0.04

5. Competing Trials

• There are over 100 Phase I-IV studies planned or ongoing for MASH, T2DM, and obesity.
• GLP-1 trials for T2DM and obesity are competing for the same patient pool as MASH trials.

6. Availability of Qualified Study Sites

• IQVIA's global MASH site network includes >760 investigators across 61 countries, with >90% having experience in MASH or other metabolic disorders.
• Site capabilities vary by region and phase, with North America (NA) having the highest percentage of qualified sites (89% for Phase IIB/III).
• Key technologies required for MASH trials include:
  • Elastography
  • MRI-PDFF
  • Liver biopsy
  • MRE
  • LiverMultiScan®

7. Additional Considerations

• Access to medical records is critical for identifying high-risk MASH patients, with 83% of NA investigators reporting access to searchable EMRs or CTMS.
• Transient elastography is not standard of care in all regions, but is increasingly used for pre-screening.
• Liver biopsy is often used in Phases IIb and III, with most sites reporting less than 24 hours of observation post-procedure.

Key Information

• GLP-1s have become a major factor in MASH trial enrollment, due to their efficacy in treating T2DM and obesity.
• Enrollment rates have declined significantly in the U.S., with a 83% drop from 2012–15 to 2020–23.
• Country selection should consider:
  • GLP-1 saturation
  • Competition from other trials
  • Availability of qualified sites
• IQVIA's databases (MIDAS® and MASH Site Network) provide valuable insights into GLP-1 utilization and site capabilities.
• Site-level feasibility is influenced by local access to GLP-1s, affordability, copays, and alternative weight loss providers.

Conclusion

• MASH clinical trials face increased challenges in patient enrollment due to GLP-1 accessibility.
• A predictable and diversified approach is necessary for future MASH trials to mitigate enrollment delays.
• Sponsors should tailor their strategies to evaluate country-specific feasibility, considering saturation, competition, and site capabilities.
• While the U.S. remains a key region, less traditional countries may offer more favorable enrollment potential for future trials.