LPCN 1148 Achieves Phase 2 Study Endpoints in Cirrhosis Management

Jennifer Lai, MD, MBA

Credit: UCSF Health

New topline results from a phase 2 study revealed LPCN 1148, an oral drug candidate, achieved its primary end points in the clinical management of cirrhosis, specifically the prevention of overt hepatic encephalopathy (OHE) recurrence and the treatment of sarcopenia.¹

LPCN 1148 is targeted to be a first-in-class product candidate with a novel, multimodal mechanism of action for cirrhosis. According to these data, individuals on LPCN 1148 therapy demonstrated an increase in Skeletal Muscle Index (SMI) at 24 weeks, with maintenance through 52 weeks, and fewer OHE events, than placebo-treated patients.

Encouraged by these positive results, Lipocine Inc. has announced plans to meet with the US Food and Drug Administration (FDA) to evaluate a development path to filing a New Drug Application (NDA).

“The rapid and sustained increases in muscle mass seen in this study with LPCN 1148 are very exciting, especially as there are currently no FDA-approved pharmacotherapeutics for sarcopenia in cirrhosis,” Jennifer Lai, MD, MBA, professor of medicine, University of California-San Francisco, and the study's principal investigator, said in a statement.¹

LPCN 1148 is comprised of testosterone dodecanoate, a unique androgen receptor agonist.² The product is targeted as a modified intervention option to create potential benefits for managing cirrhosis and any associated comorbidities.

The multi-center, phase 2 study enrolled and dosed 29 patients across 8 centers in the US, intending to evaluate the efficacy and safety of LPCN 1148 in men with cirrhosis and sarcopenia. Primary endpoints included a change in L3-SMI, measured at baseline to week 52, with a primary measurement at week 24. Key secondary endpoints included rates of hepatic encephalopathy and the safety and tolerability of LPCN 1148.

Upon analysis, all LPCN 1148-treated participants (n = 15) and 10 of 14 placebo participants completed week 24 of the study, with ≥1 available post-baseline CT scan. Analysis revealed those who received LPCN 1148 had a significant (P <.01) increase in L3-SMI of 4.1 cm2/m2 (8.8%) at Week 24. The increase was maintained until week 52 (4.1 cm2/m2) in the open-label extension period.

Individuals who received placebo and began receiving LPCN 1148 also exhibited a notable increase in L3-SMI as early as 12 weeks after initiation (Week 36, 7.4 cm2/m2; 15.1%) with maintenance through Week 52 (8.1 cm2/m2; 16.7%).

“The stability of improvement in sarcopenia and encephalopathy provides proof of concept that sarcopenia correction with LPCN 1148 may provide benefit to patients with decompensated cirrhosis and reduce the risk of breakthrough encephalopathy,” Arun J. Sanyal, MD, director, Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, added in a statement.¹

Regarding key secondary endpoints, most participants (n = 22; 76%) had experienced HE before the study, with similar numbers of these participants in each study arm. At Week 24, LPCN 1148 treatment was linked to significantly (P <.05) fewer cases of recurrent OHE (1 versus 6), a potential FDA-approvable endpoint.

In the open-label period, two cases of OHE were observed, including one that received the product since day 1 of the study and one that began receiving the product at week 24. The average time to first OHE recurrence was longer with LPCN 1148 treatment than with placebo (183 days vs. 35 days).

Across the study period, LPCN 1148 was well-tolerated. Individuals who switched from placebo to LPCN 1148 experienced fewer severe adverse events, and all participants on LPCN 1148 experienced shorter hospitalization. Two deaths were reported in placebo-treated participants and one death in LPCN 1148-treated participants in the study period.

Lipocine has announced plans to share additional results on other secondary endpoints at upcoming annual scientific meetings.

“Cirrhosis management is a significant unmet medical need with a strong pharmaco-economic rationale,” Mahesh Patel, president and CEO of Lipocine, added in a statement.¹ “...If approved, this treatment is a compelling opportunity with the potential to be the standard of care as a mono or adjunct therapy in managing advanced cirrhosis.”

References

1. _{Lipocine announces positive Week 52 results from LPCN 1148 phase 2 study in patients with cirrhosis. Lipocine Investor Room. March 28, 2024. Accessed March 28, 2024. https://ir.lipocine.com/2024-03-28-Lipocine-Announces-Positive-Week-52-Results-from-LPCN-1148-Phase-2-Study-in-Patients-with-Cirrhosis.}
2. _{LPCN 1148. Lipocine. September 29, 2021. Accessed March 28, 2024. https://www.lipocine.com/pipeline/lpcn-1148/.}