Non-Cirrhotic NASH – LPCN 1144
Product Candidate: LPCN 1144
A differentiated approach for favorable benefit to risk profile in treatment of MASH.
Product Attributes:
LPCN 1144 comprises a novel androgen receptor agonist prodrug for oral administration that targets the underlying causes of Metabolic Dysfunctional-Associated Steatohepatitis (MASH). It is under development for treatment for pre-cirrhotic MASH. US FDA has granted Fast-Track Designation for development of LPCN 1144.
LPCN 1144, through its bioidentical active, is expected to have a favorable benefit-to-risk profile with superior MASH resolution and/or fibrosis improvement with good Tolerability for chronic use. Furthermore, It has the potential to address sexual and mental dysfunctions and improve body composition (improve muscle mass with loss of fat mass), common comorbid conditions of MASH.
The key outcomes from a Phase 2 paired biopsy clinical study are the following:
- Met the pre-specified histological regulatory endpoint of MASH resolution with no worsening of fibrosis
- Changes in liver fat, key liver enzymes, body composition support beneficial treatment effects
- Treatment effect and safety consistent in hypogonadal and eugonadal men
- OLE trial demonstrates safety and efficacy with 72 weeks of LPCN 1144 treatment
- Well-tolerated with an overall safety profile comparable to placebo
About Indication:
MASH (Metabolic Dysfunction-Associated Steatohepatitis) refers to a more advanced stage of MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease). This condition indicates a condition of damage to the liver with inflammation and is often accompanied by fibrosis (scarring).
MASH is an advanced state of non-alcoholic fatty liver disease (“NAFLD”) that can progress to a cirrhotic liver or liver failure, require liver transplant, and can result in hepatocellular carcinoma/ liver cancer and death. Progression of NASH to end-stage liver disease is one of the leading causes of liver failure requiring liver transplantation. Importantly, beyond these critical conditions, NASH and NAFLD patients additionally suffer heightened cardiovascular risk and die more frequently from cardiovascular events than from liver disease.
NAFLD/NASH is becoming more common due to its strong correlation with obesity and metabolic syndrome, including components of metabolic syndrome such as diabetes, cardiovascular disease and high blood pressure.
Stem Cell Res Ther. 2025 Mar 11;16(1):130. doi: 10.1186/s13287-025-04238-0. https://stemcellres.biomedcentral.com/articles/10.1186/s13287-025-04238-0.
Prevalence: 20% to 30% of the U.S. population is estimated to suffer from NAFLD, with a large portion of that group, 15% to 20%, progressing to MASH. Approximately 50% of MASH patients are adult males. In men, especially with comorbidities associated with NAFLD/MASH, testosterone deficiency has been associated with an increased accumulation of visceral adipose tissue and insulin resistance, which could be factors contributing to NAFLD/MASH.
MASH is a chronic disease with few to no overt symptoms. Currently, available options present tolerability challenges with low efficacy. There remains an unmet need for a treatment option for chronic use that is oral, patient-friendly, with a favorable benefit-to-risk profile acceptable risk-benefit profile and also addresses some of the sexual, mental, and muscle disorder comorbidities in patients with MASH.
A healthy liver contains less than 5% fat, but a liver in someone with MASH can contain more than 20% fat. Both LPCN 1144 treatment arms met with statistical significance the pre-specified accelerated approval regulatory endpoint of MASH resolution with no worsening of fibrosis based on MASH CRN scoring. Additionally, both treatment arms showed substantial improvement of the observed MASH activity in steatosis, inflammation, and ballooning.
In November 2021, the FDA granted Fast Track Designation to LPCN 1144 as a treatment for non-cirrhotic MASH. The Fast Track program is designed to accelerate the development and expedite the review of products, such as LPCN 1144, which are intended to treat serious diseases and for which there is an unmet medical need.