A New Drug Offers Hope For A Common, Life-Threatening Liver Disease

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no current cure, but a drug called resmetirom may offer a lifeline for millions of patients, promoting a better quality of life and increased longevity.

Addendum: The FDA granted resmetirom accelerated approval on March 14, 2024.

Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease (NAFLD), a condition in which the liver builds up excessive fat deposits. A progressive disease with no current cure, it affects millions worldwide, including about 1.5-6.5% of U.S. adults. With its potential to evolve into cirrhosis and even liver cancer, the disease casts a long shadow over patients' lives and creates a significant burden on healthcare systems. However, a recent Phase 3 clinical trial published in the New England Journal of Medicine offers hope that a novel drug, resmetirom, will be the first FDA-approved treatment for NASH.

NASH, the “silent disease.”

NASH often progresses without symptoms until significant damage has been done. Characterized by the accumulation of fat and inflammation in the liver, it disproportionately affects individuals with obesity, Type 2 diabetes, and metabolic syndrome. Lifestyle changes are currently the cornerstone of management, but current options offer limited benefits for reversing liver damage, leaving patients with few choices. And terminal liver disease is a most unpleasant way to shuffle off this mortal coil.

The MAESTRO-NASH Study: A Game Changer?

The multi-institution Phase III MAESTRO-NASH trial enrolled almost 1,000 participants with varying degrees of NASH and liver fibrosis, the formation of an abnormally large amount of scar tissue. This diverse group received either resmetirom at two different dosage levels or a placebo. The results were, if not overwhelming, at least suggestive:

  • Efficacy against NASH: NASH resolution with no worsening of fibrosis was achieved in 25.9% of patients who received the 80mg dose of the drug and 29.9% of those who received the 100mg dose, compared with 9.7% of those in the placebo group.
  • Fibrosis Improvement: Resmetirom reversed structural damage to the liver, with over 24% of patients in both treatment groups experiencing at least one stage of fibrosis reduction. That is significantly higher than the 14.2% improvement observed in the placebo group, demonstrating the drug's ability to improve a crucial aspect of NASH progression.
  • Safety: The frequency of serious adverse events was similar across the three groups -- 10.9% in the 80mg resmetirom group, 12.7% in the 100mg resmetirom group, and 11.5% in the placebo group.

Beyond Numbers: Benefit to Patients and Reduced Burden on Healthcare

The above results translate into tangible benefits for NASH patients, potentially preventing future complications like cirrhosis and cancer. Moreover, the impact on healthcare costs will be substantial. Untreated NASH exacts a $32 billion annual burden in the U.S. alone, with costs rising as the disease progresses. Early intervention with an effective treatment like resmetirom will reduce those costs by preventing the need for expensive downstream interventions like liver transplants.

Navigating the Roadblocks: Cost and Accessibility

Although the potential benefits for patients and healthcare systems are undeniable, questions around cost and accessibility will inevitably arise. Resmetirom is likely to be an expensive medication, raising concerns about equitable access for patients who need it most.

However, focusing on the drug's cost may miss the bigger picture, given that early intervention could significantly reduce overall healthcare costs associated with NASH management. Additionally, the societal burden of the disease goes beyond direct costs, encompassing lost productivity and decreased quality of life for patients and their families.

Addressing the complexities of cost and accessibility will require a collaborative effort. Pharmaceutical companies, healthcare providers, policymakers, and patient advocacy groups must work together to ensure:

  • Affordable drug pricing: Strategies like value-based pricing and patient assistance programs can help make resmetirom accessible to those most in need.
  • Improved healthcare system efficiency: Streamlining diagnostic pathways and integrating NASH management into primary care can expedite early intervention and potentially reduce overall healthcare costs.
  • Increased research and development: Continued monitoring will be crucial to ensure the long-term safety and efficacy of resmetirom and explore treatment combinations.

Beyond MAESTRO-NASH: Building on the Momentum

Although the MAESTRO-NASH trial appears to offer sufficient evidence to lead to FDA approval, long-term safety evaluations of resmetirom are still underway. Continued research is crucial to ensure the drug's long-term efficacy and safety. Moreover, exploring the use of resmetirom on specific patient populations and optimizing treatment regimens requires further study.

Despite the remaining questions, resmetirom appears to offer signifcant promise to millions living under the shadow of NASH.