Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

This week’s study is…

Randomized, controlled trial of the FGF21 analogue pegozafermin in NASH

We previously published about this research in a story titled “Pegozafermin: This Novel Treatment Could Improve Liver Health in NASH” which can be found here. The study was originally published in the research publication The New England Journal of Medicine. You can read the abstract of the study here. 

This study was conducted by the University of California San Diego School of Medicine.

What Happened?

Pegozafermin is an experimental treatment that functions as an analogue of fibroblast growth factor 21 (FGF21), a peptide secreted by the liver. FGF21 controls the metabolism of lipids in the liver, as well as energy use in the body overall. Prior research has shown that it is capable of reducing liver fat and body weight. In addition, FGF21 can lower insulin and glucose levels in the blood.

In this phase 2b clinical trial, the research team sought to understand if treatment with pegozafermin could have beneficial effects on patients living with nonalcoholic steatohepatitis (NASH), an advanced form of fatty liver disease characterized by fibrosis, or scarring. 222 patients participated in the study, and all had biopsy confirmed NASH and moderate to severe (stage F2 to F3) liver scarring. The principal endpoint for this trial was improvement in fibrosis, which was defined as reduction by at least one stage on a scale ranging from zero to four, with a higher number indicating worse severity. Meanwhile, other effects of the disease couldn’t worsen. The other endpoint was resolution of NASH without worsening fibrosis. These endpoints were evaluated at 24 weeks of treatment.

Patients received either a placebo or a subcutaneous dose of the drug at doses of 15mg or 30mg each week; or a 44mg dose every two weeks. The patients that received a high dose of pegozafermin (44mg) saw a 27% improvement in scarring, while only 7% of the placebo group saw improvement. The 15mg group saw a 22% improvement and the 30mg group saw a 26% improvement. As for safety concerns, nausea was the most widely reported side effect.

The research team concluded that pegozafermin demonstrated significant benefit for the participants and could lead to improved outcomes in people living with nonalcoholic steatohepatitis.

About Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a type of liver disease in which fat is deposited in the liver independent of excessive alcohol consumption. This disease can progress rapidly. Risk factors include metabolic syndrome and insulin resistance. There also appears to be some genetic component to the disease as well. This condition also increases the risk of other health problems and liver cancer. Men also seem to be at greater risk, getting the disease as almost twice the rate that women do. Symptoms of nonalcoholic steatohepatitis include jaundice, malaise, fatigue, and abdominal pain or discomfort. Without treatment, the liver can become scarred, and the patient may need a liver transplant. However, the condition can also be managed with proper diet, the use of certain medications, and exercise. To learn more about nonalcoholic steatohepatitis, click here.

Why Does it Matter?

Nonalcoholic fatty liver disease (NAFLD) is currently on the arise around the world. According to the National Institutes of Health (NIH), almost a quarter of the US population (~24%) have NAFLD, and six percent have nonalcoholic steatohepatitis. With these conditions constituting an emerging global health problem, the need for new therapies to treat them is becoming more urgent. The US Food and Drug Administration (FDA) hasn’t approved any treatments for NASH. Therefore, the promising findings from this trial could be of utmost importance in helping improve the lives of patients:

“NASH can adversely impact the quality of life in patients and can progress to cirrhosis. Its complications can lead to death or liver transplantation. Our findings will further the science of this disease and provide a potential new treatment option to those affected by NASH-related fibrosis.” – Rohit Loomba, MD, first author, Chief of the Division of Gastroenterology and Hepatology, UC San Diego School of Medicine

Pegozafermin appears to have the ability to be a decisive, disease-altering treatment so far, meaning that it could help patients avoid the worst effects of NASH:

“The study’s results show that the new potential treatment not only improves fibrosis but also improves inflammation and liver injury along with significant improvements across multiple non-invasive biomarkers of NASH activity and scarring,” – Loomba

This drug will continue to be evaluated in a future phase 3 trial, which will be international in scope, have a longer treatment duration, and include a much larger and more diverse patient population.