ASHP Midyear: New Therapies Are on the Horizon for Fatty Liver Disease, But Access Challenges Remain

The management of non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated fatty liver disease (MAFLD), has traditionally focused on lifestyle modifications and managing comorbid conditions like diabetes and cardiovascular disease, said Kathryn Litten, PharmD, clinical assistant professor at the University of Texas at Austin College of Pharmacy. The recent approval of resmiterone, which works by decreasing liver inflammation and promoting healthy liver cell growth, represents an important milestone. Additionally, GLP-1 receptor agonists have shown benefits not only for weight loss and diabetes management, but also in reversing fatty liver and reducing fibrosis. These newer medications hold promise in preventing the progression to cirrhosis and liver cancer. Yet access challenges remain, as the high costs and potential insurance requirements for these brand-name therapies can limit patient access, especially compared to older, more affordable options like pioglitazone.

Pharmacy Times: What is the current standard of care for managing MASLD, including lifestyle modifications and pharmacological interventions?

Kathryn Litten: The current statement of care for management of NAFLD has really just been lifestyle modifications and also managing those comorbid disease states, specifically cardiometabolic disease states that do have a strong conjunction with non-alcoholic fatty liver disease, or actually has now changed its name to metabolic dysfunction-associated fatty liver disease, and so managing those disease states like diabetes, hyperlipidemia, hypertension, and even [chronic kidney disease (CKD)] are so important. Lifestyle changes are a big part of those, as well as helping with liver health and so things such as weight loss and abstention from alcohol are really important.

Pharmacy Times: Are there any emerging therapies in the pipeline for MASLD?

Kathryn Litten: Oh my gosh, there are over 100 emerging therapies in the pipeline for the management of this disease state. It's been really exciting to see how many different mechanisms that people are trialing. A lot of them, unfortunately, do or have failed trials. But right now, we actually recently, in March of this year, had the first drug that was approved for this disease state. So it's definitely an emerging area where a lot of people are trying to target and find the drugs that will really help these patients.

Pharmacy Times: Do any of these novel therapies differ from existing treatments in terms of their mechanisms of action?

Kathryn Litten: Prior to this year, a lot of our management, like I mentioned, was related to treating those comorbid conditions. One of the biggest is weight loss, and so we were using a lot of the [glucagon-like peptide (GLP)-1] receptor agonists in order to help facilitate that weight loss. We're actually seeing new trials coming out that on top of helping with weight loss, and lowering blood sugar, and cardiovascular benefits that we see with these drugs, they're actually helping reverse fatty liver and so it's really great that we're seeing benefits across the board with that drug. We're familiar with that mechanism because it can help with decreasing insulin production. It can help with promoting satiety and slowing down digestion and like that. So that's its main mechanism of action. The new medication that just got approved, called resmiterone is a thyroid hormone kind of receptor works by decreasing liver inflammation related to lipid production, and it can also help with hepatic cell turnover and promoting growth of healthy liver cells, and so this is very different kind of mechanism of actions. Other drugs we're looking at pioglitazone, which is a [peroxisome proliferator-activated receptor (PPAR)], can help with liver disease, and then a lot of other mechanisms, like I said, are kind of on the horizons related to gut inflammation, lipid production, anti diabetes medications. So lots of things out there are being looked at, and so we're just waiting to find one that can really help.

Pharmacy Times: What are the potential benefits of these new therapies in terms of improving liver function and reducing the risk of liver complications?

Kathryn Litten: I think these have really great benefits. I think that liver disease is a progressive kind of chronic disease state, and so the biggest things that we can do is help prevent that progression. We're seeing drugs like GLP-1s and the resmedarone, we're seeing them actually reduce fibrosis on the liver. We're seeing them resolve the fattiness of the liver. And so those are the things that will prevent you from progressing to cirrhosis and progressing to liver cancer, and so these are all really exciting things that can help a lot of patients across the US.

Pharmacy Times: What are the potential safety concerns associated with these emerging therapies?

Kathryn Litten: So the main [adverse] effects associated with the GLP-1 and resmiterone are [gastrointestional] things like diarrhea, constipation, cramping, vomiting, nausea, those are the main [adverse] effects that we're looking out for, and we're hoping to titrate the drugs to avoid that for most of our patients. Both of these drug classes are associated with a small risk of gallbladder disease. The GLP-1s also have risks of rare risk of pancreatitis and a black box warning for medullary thyroid disease in your family or a personal history. But overall, we're seeing these drugs being really safe, really tolerable medications.

Pharmacy Times: How do the costs of these new therapies compare to existing treatments, and will the cost affect access to these treatments?

Kathryn Litten: Some of the drugs that we have a little bit of data on like pioglitazone and even vitamin E can be cheap and available to most patients, but they may not be as impactful as some of the newer agents, like the GLP-1s and resmiterone. The GLP-1s and resmiterone being brand name, products are really expensive. The GLP-1s are also only indicated for patients who have diabetes and who have diabetes and obesity. They're actually just FDA approved for those patients, and so they may have more difficulty accessing those through insurance programs. Right now, some insurances do require liver biopsies for our patients to access resmiterone, so on top of it being an expensive medication, there may be other requirements to getting access to that medication, but there are, you know, coupons and savings programs and prescription assistance programs that the manufacturers do offer. So it's important to talk to your doctor about the options and for us as pharmacists to be able to understand the requirements of these drugs and which patients would be able to access them.