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Also known as MGL-3196, MGL-3196 Tablet, MGL-3196 (resmetirom)
Resmetirom · 16 trials · 11 indications
Any event of all-cause mortality, liver transplant, ascites, hepatic encephalopathy, gastroesophageal variceal hemorrhage, and confirmed increase of MELD score from \<12 to \>/= 15 due to liver disease
1. Proportion with resolution of NASH (ballooning 0, inflammation 0,1) associated with at least 2-point reduction in NAFLD Activity Score (NAS) without worsening of fibrosis stage OR 2. Proportion with at least a 1-point improvement in fibrosis stage with no worsening of NAS
The Composite Clinical Outcome is composed of all-cause mortality, liver transplant, and significant hepatic events (including hepatic decompensation events \[ascites, encephalopathy, or gastroesophageal variceal hemorrhage\], histological progression to cirrhosis, and a confirmed increase of MELD score from \<12 to ≥15).
Safety and tolerability will be assessed by the incidence and severity of adverse events, serious adverse events, clinical laboratory evaluations, vital signs, 12-lead electrocardiograms, physical examinations, and other protocol-defined safety assessments.
To determine the effect of MGL-3196/Resmetirom versus matching placebo on percent change from Baseline to Week 28 in hepatic fat fraction by magnetic resonance imaging proton density fat fraction (MRI-PDFF) in patients with baseline MRI-PDFF ≥8%.
LDL-C was determined by ultracentrifugation or direct measure. Least-squares (LS) mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.
The primary endpoint was relative change in MRI-PDFF assessed hepatic fat fraction compared with placebo at Week 12 in participants who had both a baseline and Week 12 MRI-PDFF. Least squares (LS) mean was provided for the statistical comparison of MGL-3196 versus placebo.
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comparison between MGL-3196 capsules and MGL-3196 tablets
Measurement of the total radioactivity collected from blood, urine, and feces
| Arm | Type | Description |
|---|---|---|
| Resmetirom | ACTIVE_COMPARATOR | 80 mg daily |
| Placebo | PLACEBO_COMPARATOR | matching placebo daily |
| Double-blind 80 mg Daily | EXPERIMENTAL | For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 80 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52 |
| Double-blind 100 mg Daily | EXPERIMENTAL | For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 100 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52 |
| Open-label | EXPERIMENTAL | For patients assigned to open-label treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, open-label resmetirom at same dose as MGL-3196-14 for an additional 52 weeks. NASH cirrhosis patients may receive open-label resmetirom for up to an additional 66 months (ie, 52 weeks in MGL-3196-14 and up to 66 months in MGL-3196-18). |
| Open-Label 80 mg | EXPERIMENTAL | For patients with NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 80 mg for up to 66 months. |
| Open Label 100 mg | EXPERIMENTAL | For patients without NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 100 mg for 52 weeks |
| Open-Label 40 mg | EXPERIMENTAL | For NASH cirrhosis patients who enter MGL-3196-18 directly or were screen failures from MGL-3196-19, open-label resmetirom 40 mg for up to 66 months. |
| Open label: resmetirom | EXPERIMENTAL | 100 mg daily |
| Double blinded: matching placebo | PLACEBO_COMPARATOR | Placebo daily |
| Double blinded: resmetirom 80 mg | EXPERIMENTAL | 80 mg daily |
| Double blinded: resmetirom 100 mg | EXPERIMENTAL | 100 mg daily |
| Matching Placebo | PLACEBO_COMPARATOR | Placebo Daily |
| 80 mg MGL-3196 | ACTIVE_COMPARATOR | 80 mg daily |
| 100 mg MGL-3196 | ACTIVE_COMPARATOR | 100 mg daily |
| Adolescent Dose-Escalation Cohort 1 | EXPERIMENTAL | Adolescents participants 12 to 17 years of age receive the first planned dose level of oral resmetirom once daily for approximately 14 days |
| Adolescent Dose-Escalation Cohort 2 | EXPERIMENTAL | Adolescent participants 12 to 17 years of age receive the second planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data. |
| Adolescent Dose-Escalation Cohort 3 | EXPERIMENTAL | Adolescent participants 12 to 17 years of age receive the third planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data. |
| Adolescent Dose-Escalation Cohort 4 | EXPERIMENTAL | Adolescent participants 12 to 17 years of age receive the fourth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data. |
| Adolescent Dose-Escalation Cohort 5 | EXPERIMENTAL | Adolescent participants 12 to 17 years of age receive the fifth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data. |
| Child Dose-Escalation Cohort 6 | EXPERIMENTAL | Children participants 6 to 11 years of age receive the first planned dose level of oral resmetirom once daily for approximately 14 days. |
| Child Dose-Escalation Cohort 7 | EXPERIMENTAL | Children participants 6 to 11 years of age receive the second planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data. |
| Child Dose-Escalation Cohort 8 | EXPERIMENTAL | Children participants 6 to 11 years of age receive the third planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data. |
| Child Dose-Escalation Cohort 9 | EXPERIMENTAL | Children participants 6 to 11 years of age receive the fourth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data. |
| Arm 1: Resmetirom 80 or 100 mg daily - Cohort 1 | ACTIVE_COMPARATOR | - |
| Arm 2: Resmetirom 80 or 100 mg daily - Cohort 2 | ACTIVE_COMPARATOR | - |
| Arm 3: Placebo - Cohort 1 | PLACEBO_COMPARATOR | - |
| Arm 4: Placebo - Cohort 2 | PLACEBO_COMPARATOR | - |
| MGL-3196 | EXPERIMENTAL | Study Drug |
| Severe renal impairment | EXPERIMENTAL | - |
| Normal Healthy Match | EXPERIMENTAL | Matched to severe renal impairment |
| MGL-3196 100 mg tablet plus Clopidogrel 75 mg tablet | EXPERIMENTAL | - |
| MGL-3196 100 mg tablet plus Pioglitazone 15 mg tablet | EXPERIMENTAL | MGL-3196 administered orally plus Pioglitazone administered orally on 2 separate days |
| 40 mg MGL-3196 Tablet | EXPERIMENTAL | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
| 60 mg MGL-3196 Tablet | EXPERIMENTAL | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
| 80 mg MGL-3196 Tablet | EXPERIMENTAL | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
| 100 mg MGL-3196 Tablet | EXPERIMENTAL | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
| Capsule then Tablet | ACTIVE_COMPARATOR | MGL-3196 Capsule on Day 1 followed by MGL-3196 Tablet on Day 5 |
| Tablet then Capsule | ACTIVE_COMPARATOR | MGL-3196 Tablet on Day 1 followed by MGL-3196 Capsule on Day 5 |
| Treatment | EXPERIMENTAL | MGL-3196 |
| Name | Type | Description |
|---|---|---|
| Resmetirom | DRUG | Randomized 80 mg |
| Placebo | DRUG | randomized matching placebo |
| MGL-3196 | DRUG | Tablet |
| Liver Biopsy | PROCEDURE | A procedure in which a needle is inserted into the liver to collect a tissue sample |
| MGL-3196 (resmetirom) | DRUG | Oral |
| 100 mg Resmetirom Tablet | DRUG | Once daily oral dose for 6 days |
| Clopidogrel | DRUG | After one-day washout period after Day 1, loading dose of 300 mg clopidogrel administered on Day 3 and then, at approximately the same time each morning, 75 mg clopidogrel administered on Days 4 to 11 |
| Pioglitazone 15mg | DRUG | Pioglitazone 15 mg tablet administered orally on 2 separate days, initially on one day alone and again after MGL-3196 has been dosed to steady-state |
| MGL-3196 Tablet | DRUG | MGL-3196 in Tablet form |
| MGL-3196 Capsule | DRUG | MGL-3196 in Capsule form |
| Atorvastatin | DRUG | - |
| Simvastatin | DRUG | - |
| Rosuvastatin | DRUG | - |
Inclusion Criteria: * A clinical diagnosis of NASH cirrhosis * At least 3 metabolic risk factors * Historical liver biopsy read as consistent with NASH cirrhosis. * Historical biopsy consistent with NASH with significant fibrosis, now with progression to cirrhosis. Or, no historical biopsy, with a ...
Resmetirom is an investigational small molecule being developed for MASH (metabolic dysfunction-associated steatohepatitis), formerly called NASH, and related liver conditions including non-alcoholic fatty liver disease and NASH cirrhosis. It is also being studied in patients with renal impairment and in children and adolescents with MASH.
Resmetirom targets THRB, the thyroid hormone receptor beta. It acts as an agonist at this receptor. By activating thyroid hormone receptor beta, resmetirom is designed to influence metabolic and liver-related pathways relevant to MASH and NASH.
Resmetirom is being developed by Madrigal Pharmaceuticals, Inc., which trades under the ticker MDGL. The company is the sponsor of the clinical trials evaluating resmetirom in MASH, NASH, and related conditions.
Resmetirom is in clinical development, with trials across Phase 1, Phase 2, and Phase 3. The Phase 3 MAESTRO-NASH-OUTCOMES study is active but not recruiting, and two Phase 2 studies in children and post-liver transplant patients are currently recruiting. It has received FDA designations including Breakthrough Therapy, Accelerated Approval, and Priority Review.
Resmetirom is being evaluated in several trials, including NCT07763015, a Phase 2 study in children and adolescents with MASH; NCT07335601, a Phase 2 study in post-liver transplant patients with MASH; NCT06397872, a completed Phase 1 study in severe renal impairment; and NCT05500222, the Phase 3 MAESTRO-NASH-OUTCOMES study in well-compensated NASH cirrhosis.
No, resmetirom is a drug candidate, not a disease. NASH, now referred to as MASH, is the liver condition that resmetirom is being developed to treat. Resmetirom is an investigational therapy, not a synonym for the disease.