LPCN 1148 – Management of Liver Cirrhosis
Novel Multi-Modal-MOA
Fewer decompensation events
Enhancing quality of life while awaiting transplant
Product Candidate: LPCN 1148
Shaping a stronger future for cirrhosis patients
Product Attributes:
LPCN 1148 is an oral androgen receptor agonist comprising testosterone laurate (TL), a unique prodrug of an endogenous hormone. It is intended for use as a monotherapy and as an adjunct to current standard of care for prevention of Overt Hepatic encephalopathy.
LPCN 1148 is targeting indications for: a) Prevention of recurrent Overt Hepatic Encephalopathy (OHE) and b) Treatment of Sarcopenia in Cirrhosis (Fast Track Designation) . In a phase 2 trial, LPCN 1148 has demonstrated improvement in sarcopenia, lower number of incidents of recurrent OHE events, and prolonged time to first recurrent effect. This study had no restrictions on use of background therapy for hepatic encephalopathy (rifaximin and/or lactulose).
About Indication:
Liver cirrhosis is the histological development of regenerative nodules in the liver surrounded by fibrous bands. Patients with cirrhosis typically have a years-long silent, asymptomatic phase (compensated cirrhosis) until decreasing liver function and increasing portal pressure move the patient into the symptomatic phase (decompensated cirrhosis). Transition to decompensated cirrhosis is marked by clinical events including ascites, encephalopathy, jaundice, and/or variceal hemorrhage. Decompensated subjects survive on average less than two years. Common causes of liver cirrhosis include alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), chronic hepatitis B and C, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and some patients have liver disease of unknown cause (cryptogenic).
Each year, cirrhosis caused more than one million deaths globally, with an estimated over 500,000 people living with decompensated cirrhosis in the U.S. Males account for 62% of those on the liver transplant (“LT”) waitlist and the economic burden (approximately $812,500/transplant) is high and continues to increase. Each year about half of the approximately 17,000 people in U.S. on the LT waitlist undergo transplant, while nearly 3,000 patients either die or are removed from the list because they were “too sick to transplant.”
Sarcopenia in Cirrhosis
Sarcopenia, the progressive loss of skeletal muscle mass, is a common and serious complication in patients with decompensated cirrhosis, affecting 30–70% of cases. Sarcopenia significantly worsens clinical outcomes and increases risks of hepatic encephalopathy, infections, prolonged hospitalizations, and mortality.
Despite its rising global burden, decompensated cirrhosis remains a condition with limited therapeutic options. Currently, liver transplantation is the only definitive intervention, yet it is constrained by organ scarcity, high cost, stringent eligibility criteria, and high waitlist mortality.
Among the most pressing unmet need in this population are interventions that reduce the frequency and severity of hepatic encephalopathy (HE) and preserve or restore muscle mass. The current standard of care for HE involves rifaximin and/or lactulose, which primarily work by reducing the amount of ammonia absorbed by the gastrointestinal (GI) tract.
Despite standard of care use, many patients continue to experience recurrent or persistent episodes of HE (i.e., breakthrough HE). These therapies have also shown reduced efficacy in patients with higher MELD scores, highlighting limitations in addressing the underlying pathophysiology of HE.
Furthermore, sarcopenia is highly prevalent in cirrhosis, contributing to clinical deterioration, including increased HE risk, impaired liver transplant outcomes, and reduced survival. Muscle plays a key role in ammonia metabolism, providing a mechanism by which improving sarcopenia may reduce the risk of HE recurrence. Currently, there are no FDA-approved therapies specifically indicated for sarcopenia in men with cirrhosis, underscoring a critical gap in the treatment landscape.