Approval Probability
TA Base Rate
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ML Risk
Label indication REZDIFFRA is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic nonalcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). This indication is approved under accelerated approval based on improvement of NASH and fibrosis [see Clinical Studies (14) ] . FDA label
Also known as MGL-3196, MGL-3196 Tablet, MGL-3196 (resmetirom)
Resmetirom · 17 trials · 12 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.
Physical examination findings will be assessed by the Investigator and include general appearance, skin, head and neck, heart, lungs, abdomen, extremities, and neuromuscular assessments. After Screening and successful Randomization, physical examinations may be targeted to evaluation of new symptoms or signs.
Body temperature will be measure in °C, resting heart rate in beats per minute, respiratory rate in breaths per minute, systolic blood pressure in mmHg, and diastolic blood pressure in mmHg
Resting heart rate will be measured in beats per minute (bpm)
Respiratory rate will be measured in breaths per minute.
Resting seated systolic blood pressure will be measured in millimeters of mercury (mmHg)
Resting seated diastolic blood pressure will be measured in millimeters of mercury (mmHg)
Hematology laboratory parameters include hemoglobin, hematocrit, red blood cell count, white blood cell count, platelet count, red blood cell indices, and differential leukocyte counts. The number of participants with clinically significant abnormalities, as determined by the Investigator, will be summarized by treatment group.
Blood chemistry laboratory parameters include measures of hepatic function, renal function, glucose metabolism, pancreatic function, electrolytes, bilirubin, and serum proteins. The number of participants with clinically significant abnormalities, as determined by the Investigator, will be summarized by treatment group.
Urinalysis parameters include pH, specific gravity, protein, glucose, ketones, bilirubin, blood, nitrite, urobilinogen, and leukocyte esterase. The number of participants with clinically significant abnormalities, as determined by the Investigator, will be summarized by treatment group.
Cmax after administration
Tmax after administration
AUC(0-Last) after administration
t1/2 after administration
AUC (0-last) after administration
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 |
| Arm 1 - Resmetirom | EXPERIMENTAL | Participants will receive resmetirom orally once daily for 24 weeks. Resmetirom dose will be based on actual body weight: 80 mg once daily for participants weighing \<100 kg and 100 mg once daily for participants weighing ≥100 kg. Dose reduction by 20 mg will be implemented for concomitant use of a moderate CYP2C8 inhibitor, as specified in the protocol |
| Arm 2 - Placebo Comparator | PLACEBO_COMPARATOR | Participants will receive matching placebo orally once daily for 24 weeks. |
| 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 oral small molecule being studied for metabolic dysfunction-associated steatohepatitis (MASH), previously called NASH. It is also being evaluated in heterozygous familial hypercholesterolemia, hepatic impairment, renal impairment, and in patients with MASH and heart failure with preserved ejection fraction. It has received FDA breakthrough therapy, accelerated approval, and priority review designations.
Resmetirom targets thyroid hormone receptor beta (THRB) and acts as an agonist. By activating THRB, it is designed to influence pathways involved in liver fat metabolism and cholesterol regulation. This mechanism is being explored in conditions such as MASH and heterozygous familial hypercholesterolemia.
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 and related conditions.
Resmetirom is in clinical development, with trials across Phase 1 and Phase 2. It is not approved for any indication. The program includes completed Phase 1 studies and ongoing Phase 2 studies in MASH, including pediatric and post-liver transplant populations.
Resmetirom is being studied in several clinical trials, including NCT07830758 in patients with MASH and HFpEF, NCT07763015 in children and adolescents with MASH, NCT07335601 in post-liver transplant patients with MASH, and NCT06397872 in subjects with severe renal impairment. These trials are evaluating safety, pharmacokinetics, and tolerability.
Yes, resmetirom is also known as MGL-3196. Other alternative names include 100 mg Resmetirom Tablet, MGL-3196 Tablet, and MGL-3196 (resmetirom). These names refer to the same investigational drug candidate.