Sponsored Insight
How can we harness the power of science to change the lives of people with cardiometabolic diseases?
It is a question we need to keep asking ourselves across the biopharmaceutical industry.
Despite advances in prevention and treatment, cardiometabolic diseases remain the leading cause of death in the U.S. Key risk factors for developing these conditions (fatty liver disease, hyperlipidemia, atherosclerosis, and abdominal obesity, etc.) can include uncontrolled high blood pressure or high levels of low-density lipoproteins (LDL) cholesterol, as well as smoking.1 Among cardiometabolic diseases, two diseases – non-alcoholic steatohepatitis (NASH) and severe hypertriglyceridemia (SHTG) – have no or limited treatment options. People with these conditions are waiting for new hope, and we at 89bio are pushing for answers.
Going where the need is significant
As an industry, we can and must do better for patients with NASH and SHTG – the need is urgent. NASH, a severe form of fatty liver disease, is a chronic and progressive condition. As fat accumulates in the liver, it can become inflamed leading to scarring, or fibrosis. In later stages, NASH can cause cirrhosis, liver failure and liver cancer.2 But its impact is not limited to the liver, NASH raises the risk of cardiovascular disease, too, which can be fatal.3
The consequences of NASH have not been studied enough, especially considering the number of cases continues to rise, fueled by the obesity epidemic. By 2030, NASH is projected to affect 27 million Americans, a large rise from 16.5 million in 2015.4 Despite the significant individual, societal and economic impact of NASH, there are no FDA-approved treatments. Instead, patients must rely on lifestyle changes, including diet, exercise and medications to induce weight loss.5
There is a similar situation happening for patients with SHTG. Although the industry has made significant advances in the treatment of high LDL cholesterol, treatments for SHTG continue to elude science. A severe form of elevated triglycerides, which are a type of fat or lipid in the blood, SHTG is another harmful cardiometabolic disease that impacts up to four million adults in the U.S.6
The condition is defined as having a fasting triglyceride level of 500 mg/dL and higher as measured by a simple blood test. The standard of care for SHTG, which includes lifestyle changes and treatment with fish oils (icosapent ethyl and omega-3 ethyl esters), fibrates, niacin, and statins, is often suboptimal. Existing therapies do not provide broader metabolic benefits or may even worsen other co-morbid risk factors for cardiovascular disease.
Even with treatment, studies suggest about half of people with SHTG are unable to lower their triglyceride level under that threshold. With ineffective treatment options, people are left at risk to develop acute pancreatitis and cardiovascular diseases.
Developing breakthrough medicines
Science is the key to breaking this cycle of suboptimal treatments and to closing the gaps in cardiometabolic care among people with NASH and SHTG. 89bio is dedicated to the development of therapies that will provide true medical innovation. We knew the road to developing an effective treatment for cardiometabolic diseases like these wouldn’t be easy. But we won’t let the fact that it hasn’t been done before deter us from doing what is needed. In the last four years alone, we have shown proof of concept and advanced two indications to the point of late-stage clinical studies, and this is just the beginning.
We believe the answer for an effective treatment option could be our lead investigational medicine, pegozafermin, which is a specially engineered glycoPEGylated analog of fibroblast growth factor 21 (FGF21). FGF21 is an endogenous hormone that regulates energy expenditure and glucose and lipid metabolism. FGF21 plays multiple roles in the body, such as reducing the formation of new fat in the liver and lowering systemic levels of triglycerides in the blood. A treatment that targets FGF21 could have diverse, beneficial biological effects on the liver, fat, muscles, and more.
Data from our Phase 1b/2a proof-of-concept study in patients with NASH or presumed NASH suggests pegozafermin can meaningfully reduce fat in the liver, improve key markers of liver injury (ALT), and improve lipid levels and glycemic markers that are indicative of the multiple co-morbidities that worsen the disease.7 Additionally, results from an open-label expansion cohort of patients with biopsy-proven NASH in the same study demonstrated that treatment with pegozafermin had clinically meaningful changes in histology endpoints, including improved fibrosis and NASH resolution.8 Combining strong efficacy and a favorable tolerability profile with weekly or every-two-week dosing convenience, pegozafermin has the potential to be a mainstay treatment for NASH. We are looking forward to seeing the results from our ongoing Phase 2b trial, ENLIVEN later this quarter.
Given the positive impact we saw pegozafermin had in meaningfully reducing triglycerides and providing other metabolic benefits, we also made the decision to develop this metabolic hormone for the treatment of SHTG. Results from our Phase 2b study, ENTRIGUE, in patients with SHTG showed that treatment with pegozafermin may offer robust and durable reductions in triglycerides while addressing other metabolic issues common in patients with the condition, including improvements in key markers of cardiovascular risk, reductions in liver fat and improvements in glycemic control markers.9 Based on these positive results, we are pleased to be advancing pegozafermin into a Phase 3 program in SHTG this year.
Based on all the evidence and promise we have observed so far, we are confident in the progression of the clinical development of pegozafermin. Our team won’t stop until we have better medicines – and new hope – for people with NASH, SHTG, and other serious cardiometabolic disorders.
1. Fryar CD, Chen T-C, Li X. Prevalence of uncontrolled risk factors for cardiovascular disease: United States, 1999–2010 pdf icon[PDF-494K]. NCHS data brief, no. 103. Hyattsville, MD: National Center for Health Statistics; 2012. Accessed May 9, 2019.
2. Benedict M, Zhang X. Non-alcoholic fatty liver disease: an expanded review. World J Hepatol. 2017; 9:715-732. doi:10.4254/wjh.v9.i16.715.
3. Patil, R., & Sood, G. K. (2017, May 15). Non-alcoholic fatty liver disease and cardiovascular risk. World journal of gastrointestinal pathophysiology. Retrieved January 31, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437502/
4. Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018;67(1):123-133. doi:10.1002/hep.29466.
5. Dajani A, AbuHammour A. Treatment of nonalcoholic fatty liver disease: Where do we stand? an overview. Saudi J Gastroenterol. 2016;22(2):91-105. doi:10.4103/1319-3767.178527.
6. Karalis DG. A review of clinical practice guidelines for the management of hypertriglyceridemia: a focus on high dose omega-3 fatty acids. Advances in Therapy. 2017; 34:300-323. doi:10.1007/s12325-016-0462-y.
7. Loomba R, Lawitz EJ, Frias JP, et al. Safety, pharmacokinetics, and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study. Lancet Gastroenterol Hepatol. 2023;8(2):120-132. doi:10.1016/S2468-1253(22)00347-8
8. Data on file. 89bio. January 24, 2022.
9. Pegozafermin for the Treatment of Severe Hypertriglyceridemia: A Randomized, Double-blind, Placebo-controlled Phase 2 Study (ENTRIGUE STUDY). Presented at the Cardiometabolic Health Congress October 19-22, 2022.