Oral LPCN 1148 improves sarcopenia and hepatic encephalopathy in male patients with cirrhosis: A randomized, placebo-controlled phase 2 trial

Benjamin J Bruno; Joshua C Weavil; Jonathan Ogle; Nachiappan Chidambaram; Elizabeth J Carey; Christopher J Danford; Zarchary P Fricker; Joseph S Galati; William M Lee; Parvez S Mantry; Kirti Shetty; Anthony DelConte; Mahesh V Patel; Jennifer C Lai; Arun J Sanyal

doi:10.1097/HEP.0000000000001146

Oral LPCN 1148 improves sarcopenia and hepatic encephalopathy in male patients with cirrhosis: A randomized, placebo-controlled phase 2 trial

Hepatology. 2024 Nov 8. doi: 10.1097/HEP.0000000000001146. Online ahead of print.

Authors

Benjamin J Bruno¹, Joshua C Weavil¹, Jonathan Ogle¹, Nachiappan Chidambaram¹, Elizabeth J Carey², Christopher J Danford³, Zarchary P Fricker⁴, Joseph S Galati⁵, William M Lee⁶, Parvez S Mantry⁷, Kirti Shetty⁸, Anthony DelConte^{1

9}, Mahesh V Patel¹, Jennifer C Lai¹⁰, Arun J Sanyal¹¹

Affiliations

¹ Lipocine Inc., Salt Lake City, UT, USA.
² Divisions of Hepatology and Gastroenterology, Mayo Clinic Arizona, Phoenix, AZ, USA.
³ Transplant Services, Intermountain Medical Center, Murray, UT, USA.
⁴ Department of Gastroenterology, Hepatology, & Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁵ Liver Specialists of Texas, Houston, TX, USA.
⁶ Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
⁷ Research and Hepatobiliary Tumor Program, The Liver Institute at Methodist Dallas Medical Center.
⁸ Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁹ Department of Food, Pharma, & Healthcare, Saint Joseph's University, Philadelphia, PA, USA.
¹⁰ Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, California, USA.
¹¹ Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, VA, USA.

PMID: 39513970
DOI: 10.1097/HEP.0000000000001146

Abstract

Background aims: Sarcopenia is highly prevalent in patients with liver cirrhosis and is associated with adverse clinical outcomes including hepatic encephalopathy (HE). Androgen receptor agonists, ARAs, can address these conditions through multimodal mechanisms of action, however their safety and efficacy in patients with cirrhosis have not been well established.

Approach results: In this multicenter, double-blind, phase 2 trial, men with sarcopenia and cirrhosis awaiting liver transplant were randomized 1:1 to receive either oral ARA LPCN 1148 or placebo for 24 weeks (NCT04874350). The primary endpoint was the change from baseline to 24 weeks in skeletal muscle index measured by computed tomography scan of the L3 region (L3-SMI), analyzed with a prespecified modified intent-to-treat population. The secondary endpoint was the number of overt HE events. 29 participants (mean age=59 y, MELD=17) received at least one dose of LPCN 1148 (n=15) or placebo (n=14). Baseline characteristics were similar between groups. Primary endpoint analysis demonstrated an increase in L3-SMI in the LPCN 1148 group (n=15) compared to placebo (n=10), with a mean group difference of 4.4 cm2/m2 (95% CI, 1.3-7.4 cm2/m2, p=0.007). Participants in LPCN 1148 experienced fewer episodes of overt HE (CTCAE grade ≥2; p=0.02) than placebo. The number and severity of treatment-emergent adverse events were similar between arms.

Conclusions: LPCN 1148 treatment improved sarcopenia and reduced the number of overt HE episodes in men with cirrhosis and sarcopenia awaiting liver transplant. These findings support additional research on the efficacy of LPCN 1148 in treating sarcopenia and preventing HE recurrence.