Rezdiffra (resmetirom)
Research Synopsis
- Rezdiffra (resmetirom) is a new drug under investigation for treating non-alcoholic steatohepatitis (NASH), which is a serious liver condition characterized by fat accumulation, inflammation, and liver damage.
- Recent studies have indicated that resmetirom is a thyroid hormone receptor-β agonist that significantly reduces liver fat, showing a -32.9% reduction compared to -10.4% for placebo at 12 weeks, and -37.3% compared to -8.5% at 36 weeks in clinical trials.
- The drug's safety profile appears favorable, with mostly mild side effects reported during trials, bolstering its potential for broader clinical use.
- Research also highlights that resmetirom and other thyroid hormone receptor-β agonists selectively target metabolic pathways in the liver, making them promising candidates for managing NASH, which is increasingly prevalent due to rising obesity rates.
- Industry projections suggest a substantial market growth for NASH therapies, with resmetirom positioned as a frontrunner among drug candidates in phase 3 trials, alongside others like obeticholic acid and elafibranor.
- Recent reports underscore the need for effective pharmacological interventions for NASH, despite the current lack of FDA-approved drugs specifically for this condition.
- The development of resmetirom has spurred interest in thyromimetics as a therapeutic approach, with ongoing research underscoring their metabolic benefits without the adverse effects linked to traditional thyroid hormone treatments.
- Comparatively, ongoing validation of resmetirom's efficacy and safety will be crucial as researchers analyze the long-term outcomes and potential drug interactions, particularly concerning diverse patient demographics, including those with associated conditions like HIV.
Rezdiffra (resmetirom)
Liver matrin-3 protects mice against hepatic steatosis and stress response via constitutive androstane receptor.
London, UK
2 hours ago
1 Received
- Researchers are studying a liver disease called MASLD, which is getting more common because many people are becoming overweight, and they want to find better treatments.
- They looked at a protein called Matrin-3 that helps control how genes work in the liver and its role in preventing fat buildup and stress responses.
- When Matrin-3 was removed from certain mice, it made their livers worse when they ate a high-fat diet, showing that Matrin-3 is important for keeping liver health by helping a special receptor called CAR function properly.
$100 - $150
Hourly Rate
Lipid lowering in healthy volunteers treated with multiple doses of MGL-3196, a liver-targeted thyroid hormone receptor-β agonist.
London, UK
2 hours ago
1 Received
- - MGL-3196 is an oral medication targeting the thyroid hormone receptor-β, developed to treat dyslipidemia, and it was found safe in first-in-human studies, including a single ascending dose trial.
- - A two-week study showed MGL-3196 was well-tolerated at various doses (5-200 mg) without significant adverse effects, leading to a 20% reduction in free thyroxine and significant lipid improvements.
- - The highest dose of 80 mg daily produced significant reductions in LDL cholesterol (up to 30%), non-HDL cholesterol (28%), and Apolipoprotein B (24%), suggesting MGL-3196 may effectively improve lipid levels in those with mild
$100 - $150
Hourly Rate
Discovery of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile (MGL-3196), a Highly Selective Thyroid Hormone Receptor β agonist in clinical trials for the treatment of dyslipidemia.
London, UK
2 hours ago
1 Received
- The thyroid hormone (TH) has beneficial effects on lipid levels via the thyroid hormone receptor β (THR-β) in the liver, while negative effects arise from the thyroid hormone receptor α (THR-α).
- A newly identified pyridazinone compound, MGL-3196, is significantly more selective for THR-β than previous versions and is 28-fold more selective in functional assays.
- In studies, MGL-3196 demonstrated excellent safety in rats and healthy volunteers, effectively reducing LDL cholesterol and triglycerides without affecting the central thyroid axis.
$100 - $150
Hourly Rate
Therapeutics Highlights from ILC 2018, the EASL annual congress.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Phase 3 drug pipelines in the treatment of non-alcoholic steatohepatitis.
London, UK
2 hours ago
1 Received
- - Non-alcoholic steatohepatitis (NASH) is a severe liver disease that can lead to serious conditions like cirrhosis and liver failure, with liver transplantation being the only current treatment for NASH cirrhosis.
- - NASH is expected to become the leading cause of liver transplants in the USA by 2020, and while there are no approved drugs for it yet, around 196 potential therapies are under investigation, with five candidates currently in phase 3 trials.
- - The market for NASH treatments is projected to grow significantly, from $618 million in 2016 to approximately $25.3 billion by 2026, with the earliest potential drug approval expected in
$100 - $150
Hourly Rate
Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.
London, UK
2 hours ago
1 Received
- Non-alcoholic steatohepatitis (NASH) is a liver condition characterized by fat accumulation, inflammation, and liver injury, and the study focused on resmetirom (MGL-3196), a thyroid hormone receptor-β agonist, aimed at improving NASH.
- A randomized, double-blind study involved 84 participants with confirmed NASH, comparing resmetirom to a placebo over 36 weeks, assessing liver fat using MRI and liver biopsies.
- Results showed that resmetirom significantly reduced liver fat at both 12 weeks (-32.9% vs -10.4% for placebo) and 36 weeks (-37.3% vs -8.5%), with mostly mild side
$100 - $150
Hourly Rate
Improving NASH with a little help from thyromimetics.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Thyromimetics as emerging therapeutic agents for nonalcoholic steatohepatitis: rationale for the development of resmetirom (MGL-3196).
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Design, synthesis and biological evaluation of novel TRβ selective agonists sustained by ADME-toxicity analysis.
London, UK
2 hours ago
1 Received
- Triiodothyronine (T3) benefits lipid metabolism but has serious side effects like heart issues and mood disturbances, mainly due to the α isoform of thyroid hormone receptors (TRs).
- Researchers are focusing on developing selective agonists for the β isoform of TRs to gain metabolic benefits without the harmful side effects associated with T3.
- The discovery process identified new compounds, particularly derivatives 1 and 3, that showed effectiveness in reducing lipid accumulation and low toxicity during initial studies, positioning them as promising candidates for further testing.
$100 - $150
Hourly Rate
Prof Jörn Schattenberg sheds light on key treatment and diagnostic approaches to nonalcoholic steatohepatitis (NASH).
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
New Drugs for NASH and HIV Infection: Great Expectations for a Great Need.
London, UK
2 hours ago
1 Received
- There has been a rise in clinical trials for nonalcoholic steatohepatitis (NASH), but people living with HIV (PLWH) are often excluded due to drug interaction concerns with their antiretroviral therapy.
- The Steatohepatitis in HIV Emerging Research Network examines the relationship between HIV and NASH, addressing the challenges of including PLWH in these trials.
- Recent discussions focus on potential drug interactions with NASH treatments like aramchol and elafibranor, and propose a new trial design that includes PLWH as a specific subpopulation.
$100 - $150
Hourly Rate
Selective Thyroid Hormone Receptor-Beta (TRβ) Agonists: New Perspectives for the Treatment of Metabolic and Neurodegenerative Disorders.
London, UK
2 hours ago
1 Received
- Thyroid hormones (THs) are essential for growth, development, and metabolism, with their effects primarily mediated by two receptor types: TRα and TRβ.
- TRβ notably impacts liver health, while TRα is crucial for brain development; researchers strive to create TH analogs that differentiate beneficial effects from harmful ones, especially in the heart and muscles.
- Recent developments include selective thyroid hormone mimetics like Resmetirom and VK2809, showing promise as lipid-lowering agents in clinical trials, alongside newer compounds IS25 and TG68, evaluated for their effectiveness and safety.
$100 - $150
Hourly Rate
Thyroid Hormone Analogues: An Update.
London, UK
2 hours ago
1 Received
- - The development of thyroid hormone (TH) analogues aimed to enhance lipid metabolism benefits while minimizing heart-related side effects, leading to the creation of TRβ-selective compounds like GC-1 and MGL-3196 for clinical trials.
- - While some compounds successfully lowered LDL cholesterol, a phase 3 trial for eprotirome was halted due to liver complications and cartilage issues in animals, leading to the discontinuation of further projects.
- - New interest in TRβ agonists has emerged for treating nonalcoholic fatty liver disease (NAFLD), and encouraging results from clinical trials for MGL-3196 and VK2809 have been reported, alongside potential applications of TH metabolites for conditions like TH resistance and
$100 - $150
Hourly Rate
Thyroid Hormones and Thyromimetics: A New Approach to Nonalcoholic Steatohepatitis?
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis.
London, UK
2 hours ago
1 Received
- * Current guidelines suggest using pioglitazone or vitamin E for patients with NASH and significant fibrosis, but these treatments are off-label.
- * Several new medications are undergoing phase 3 clinical trials, including obeticholic acid and elafibranor, and there's hope that they may offer effectiveness similar to current treatments with fewer side effects, alongside lifestyle changes like exercise and a healthy diet.
$100 - $150
Hourly Rate
Nonalcoholic Fatty Liver Disease: A Drug Revolution Is Coming.
London, UK
2 hours ago
1 Received
- * Despite vitamin E and other medications showing some benefits, there are currently no FDA-approved drugs specifically for NASH, but several potential treatments are in phase 3 trials.
- * Future treatment approaches for NASH are likely to involve drug combinations and personalized medicine tailored to individual patient responses and different disease characteristics.
$100 - $150
Hourly Rate
Regulation of gene transcription by thyroid hormone receptor β agonists in clinical development for the treatment of non-alcoholic steatohepatitis (NASH).
London, UK
2 hours ago
1 Received
- Thyroid hormones influence metabolism in mammals, affecting cholesterol and fatty acid levels through activation of the nuclear thyroid hormone receptor (THR), with THRβ agonists showing promise for treating non-alcoholic steatohepatitis (NASH).
- The study evaluated three THRβ-agonists (GC-1, MGL-3196, and VK2809) for their selectivity and effectiveness in altering gene expression related to cholesterol and fatty acid metabolism in human liver cells and rat models.
- Results indicated that GC-1 showed comparable potency to natural thyroid hormone T3, while other compounds were significantly less effective, although VK2809's active form exhibited increased potency in certain conditions, highlighting their potential in managing metabolic
$100 - $150
Hourly Rate
Evolving Role for Pharmacotherapy in NAFLD/NASH.
London, UK
2 hours ago
1 Received
- - Nonalcoholic fatty liver disease (NAFLD) is a common and evolving condition that can progress to serious liver issues like cirrhosis and cancer, but there are no FDA-approved treatments yet, prompting active research in the area.
- - Emerging pharmacotherapies are mainly focused on improving bile acid signaling, reducing insulin resistance, and enhancing lipid management in the liver, with several drugs currently undergoing clinical trials.
- - Obeticholic acid has shown promise in phase III trials for reducing liver fibrosis in patients with nonalcoholic steatohepatitis (NASH), while other treatments are being explored in ongoing trials, highlighting the importance of tailoring therapy to specific NAFLD patient subgroups.
$100 - $150
Hourly Rate
Efficacy and safety of drugs for nonalcoholic steatohepatitis.
London, UK
2 hours ago
1 Received
- * Currently, no drugs are FDA-approved specifically for NASH, though vitamin E is recommended for non-diabetic patients, and a combination of vitamin E and pioglitazone for those with diabetes.
- * Several drugs, including obeticholic acid, are in advanced clinical trials but face setbacks, such as the recent FDA rejection of OCA due to the need for further long-term studies.
$100 - $150
Hourly Rate
Emerging therapies for the treatment of nonalcoholic steatohepatitis: A systematic review.
London, UK
2 hours ago
1 Received
- A literature search was conducted to assess the mechanism, efficacy, and safety of new agents undergoing phase 3 clinical trials for biopsy-proven nonalcoholic steatohepatitis (NASH) using specific MeSH terms and databases.
- Eleven studies were identified concerning various drugs such as obeticholic acid (OCA) and elafibranor, with OCA showing promising results for NASH resolution and a new drug approval application submitted, while elafibranor displayed no efficacy in its early trial outcomes but is undergoing further evaluation.
- The increasing prevalence of NASH and limited treatment options highlight the importance of these novel agents, which could provide effective therapies and help prevent progression to more severe liver disease.
$100 - $150
Hourly Rate