CONSHOHOCKEN, PA — Madrigal Pharmaceuticals Inc. (NASDAQ: MDGL) reported that up to 93% of patients taking its liver disease drug Rezdiffra experienced improved or stable liver stiffness measurements after approximately one year, according to real-world studies presented at a national medical conference, providing additional evidence of the treatment’s performance outside controlled clinical trials.
The findings, presented at the recent American Association for the Study of Liver Diseases’ annual meeting in Denver, also showed that up to 72% of patients remained on treatment after one year, with improvements observed among patients taking other medications for metabolic conditions.
The results offer new evidence about how Rezdiffra, also known as resmetirom, performs in routine clinical practice among patients with metabolic dysfunction-associated steatohepatitis, or MASH, a progressive liver disease associated with inflammation and scarring.
Madrigal evaluated findings from multiple independent healthcare datasets, including electronic health records, specialty pharmacy information and insurance claims.
Across four studies involving patients with paired liver stiffness measurements, 37% to 55% achieved a reduction of at least 25% after approximately one year of treatment.
Liver stiffness is measured using ultrasound elastography, a noninvasive technique used to assess changes associated with liver fibrosis.
The studies also found that most patients experienced either improvement or stabilization in liver stiffness, although the proportions varied by dataset.
In an analysis of Truveta healthcare data, 55% of 150 patients with paired measurements achieved at least a 25% reduction in liver stiffness after 12 months.
Nearly half, or 48%, experienced reductions of at least 30%, while 93% improved or remained stable. Additionally, 67% moved into a lower predefined liver stiffness category.
A separate analysis using Trio Health data examined 195 patients with paired measurements and found that 45% achieved reductions of at least 25%, while 38% achieved reductions of at least 30%.
Overall, 88% of patients in that analysis experienced improvement or stabilization.
Among another 347 patients with documented fibrosis stages in the Trio Health dataset, 44% improved by at least one stage.
A study involving 112 patients from Gastro Health and Latica found that 47% achieved liver stiffness reductions of at least 25%, while approximately 38% achieved reductions of at least 30%.
About 89% experienced improvement or stabilization. Among 46 patients whose initial liver stiffness measurements ranged from 10 to less than 20 kilopascals, 32 subsequently recorded measurements below 10 kilopascals.
At Methodist Dallas Medical Center, a smaller study of 35 patients found that 37% achieved reductions of at least 25% and 26% achieved reductions of at least 30%.
Approximately 83% of patients in that study improved or remained stable.
The consistency of the findings across separate clinical settings was a central consideration for researchers evaluating the drug’s performance outside clinical trials.
“Not every medicine delivers the same results in real-world clinical practice that we see in carefully controlled clinical trials, particularly when treating a complex, chronic disease like MASH,” stated Parvez Mantry, MD, of The Liver Institute at Methodist Dallas Medical Center.
The findings rely on noninvasive measurements associated with liver health rather than directly establishing reductions in long-term complications such as cirrhosis, liver failure or liver-related mortality.
Rezdiffra’s approved indication is based on improvements in MASH and liver fibrosis, with additional studies underway to confirm its clinical benefit.
Madrigal also examined treatment outcomes among patients with type 2 diabetes, obesity and cardiovascular conditions, including those receiving GLP-1 receptor agonists or cholesterol-lowering statins.
A subgroup analysis drawn from 2,488 patients in the Truveta dataset found statistically significant improvements in average liver stiffness and liver fat measurements across groups defined by diabetes, obesity, GLP-1 medication use and statin use.
Across those subgroups, approximately 89% to 98% of patients with paired measurements experienced improvement or stabilization in liver stiffness.
As many as 53% of patients in the reported analyses were receiving GLP-1 therapies alongside Rezdiffra.
The broader Truveta analysis found that average liver stiffness declined by 2.5 kilopascals after 12 months.
Average alanine aminotransferase, or ALT, a marker of liver injury, decreased by 16.2 units per liter.
Patients also recorded average reductions of 15.5 milligrams per deciliter in LDL cholesterol and 41 milligrams per deciliter in triglycerides.
In the Trio Health analysis, 54% of patients achieved a reduction in liver fat exceeding 40 decibels per meter using the controlled attenuation parameter measurement.
Another 48% experienced an ALT reduction of at least 20% from baseline.
An additional analysis using Optum Market Clarity data identified statistically significant reductions in liver enzymes and selected cardiometabolic measurements after 12 months.
Separate studies examined whether patients continued taking Rezdiffra after starting treatment.
Three analyses used pharmacy and administrative claims data to evaluate treatment persistence and adherence, including a retrospective study involving 11,469 patients from the CVS Healthspire database.
Across the studies, persistence reached as high as 89% at six months and 72% at 12 months.
The one-year persistence measure allowed treatment gaps of up to 60 days, meaning the reported rates reflect the studies’ definitions rather than uninterrupted daily medication use.
Adherence among patients continuing treatment was also reported to be high.
David Soergel, MD, Madrigal’s chief medical officer, described the results as evidence that treatment effects observed in the company’s Phase 3 clinical trial are also appearing in routine care.
“Across multiple studies and diverse patient populations, we are seeing robust improvements in noninvasive measures of liver health consistent with the positive results observed in the pivotal Phase 3 trial of Rezdiffra,” Soergel stated.
The real-world safety findings were generally consistent with the drug’s established clinical trial profile.
In one analysis, 11% of patients experienced at least one reported adverse event.
Diarrhea was reported in 7% of patients, nausea in 4%, itching and vomiting in 2% each, and fatigue in 1% or fewer.
Rezdiffra is prescribed alongside diet and exercise for adults with MASH and moderate to advanced liver fibrosis who do not have cirrhosis.
MASH can progress to cirrhosis, liver failure, liver cancer and the need for liver transplantation. The disease is also associated with increased cardiovascular risk.
Patients with moderate to advanced fibrosis face substantially higher risks of liver-related complications than those without fibrosis.
Rezdiffra carries warnings about potential liver injury and gallbladder-related complications, including gallstones and gallbladder inflammation.
Patients are advised to inform their healthcare providers about other medications they take because Rezdiffra can interact with certain drugs.
The medication is not recommended for patients taking gemfibrozil, and additional precautions apply to medications including clopidogrel and statins.
Its most common side effects include diarrhea, nausea, itching, abdominal pain, vomiting, dizziness and constipation.
The new findings expand the available evidence on Rezdiffra’s use in clinical practice as Madrigal continues studying the treatment’s long-term benefits for patients with MASH and liver fibrosis.
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