Potential First in Class Treatment for Cirrhosis Shows Positive Results in Phase II Trial

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Data from a Phase II trial (NCT04874350) showed promising topline findings for Lipocine Inc’s potential first in class therapy for the clinical management of cirrhosis.¹ LPCN 1148 is an oral drug that has demonstrated positive results in preventing recurrence of overt hepatic encephalopathy (OHE) and treating sarcopenia. As a result of the trial data, Lipocine said it will meet with the FDA to develop a path to filing a new drug application for the medication.

"We are encouraged with the positive results from our Phase II study. These results demonstrate that LPCN 1148 treatment benefits patients with cirrhosis who are sarcopenic and have experienced other serious decompensation events such as OHE," Mahesh Patel, PhD, president and CEO of Lipocine Inc., said in a press release "Cirrhosis management is a significant unmet medical need with a strong pharmaco-economic rationale. We believe LPCN 1148 both ameliorates sarcopenia and decreases the recurrence of OHE. 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."¹

LPCN 1148 is comprised of the androgen receptor agonist testosterone dodecanoate with a novel, multimodal mechanism of action (MOA) that has shown the potential to manage cirrhosis, as well as the comorbidities of the condition, in prior trials.²

The current 52-week, multicenter, double-blind, placebo-controlled, Phase II trial randomly assigned on a 1:1 ratio 29 sarcopenic male patients with cirrhosis who were on the liver transplant waitlist to receive either LPCN 1148 or matching placebo for 24 weeks in Stage 1 of the study. For the Stage 2 open-label extension portion, eight patients from the placebo cohort in the first stage were switched to LPCN 1148 and 11 patients from the investigational cohort continued treatment with the novel drug.³

The trial’s primary endpoint was a change in estimated whole body skeletal muscle mass (L3-SMI) at week 24, with SMI evaluated at baseline, and again at weeks 12, 24, 36, and 52, with key secondary endpoints that included rates of hepatic encephalopathy and the safety and tolerability of the drug. All patients administered LPCN 1148 (n=15) completed 24 weeks of treatment, compared with 10 of 14 patients in the placebo cohort.

Among patients administered LPCN 1148, during the initial 24 weeks, all had at least one evaluable post-baseline CT scan and 10 patients in the placebo cohort had an evaluable post-baseline CT, which qualified them for the modified intent to treat (mITT) analysis. Patients in the LPCN 1148 cohort in Stage 1 showed a significant (p<0.01) increase in L3-SMI of 4.1 cm²/m² (8.8%) at week 24, which they were able to maintain across the additional 28 weeks of the study (week 52, 4.1 cm²/m², 8.7%). Those administered placebo before switching to LPCN 1148 experienced a significant increase in SMI as early as 12 weeks following treatment with the novel therapy (week 36, 7.4 cm²/m², 15.1%), which they were able to maintain through week 52 (8.1 cm²/m², 16.7%).

In Stage 1, there was one case of recurrent OHE in patients administered LPCN 1148 compared with six in the placebo group, which investigators said is a potential FDA-approvable endpoint. In the open-label Stage 2 portion of the trial, two cases of OHE were reported, one of which occurred in a patient administered LPCN 1148 since trial initiation and one in a patient who began treatment with LPCN 1148 at week 24. The results showed that the average time to first OHE recurrence was 183 days in patients administered LPCN 1148 compared to 35 days for patients given a placebo.

In terms of safety, LPCN 1148 was found to be well-tolerated with rates and severities of adverse events (AEs) comparable to AEs reported in Stage 1 with placebo. There were fewer severe AEs reported in those who switched from placebo to LPCN 1148 and patients in the LPCN 1148 cohort had fewer total days hospitalized and shorter hospital stays.

"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,” trial principal investigator Jennifer Lai, MD, MBA, UCSF Professor of Medicine, transplant hepatologist, said in the release. “The observed trends towards improved clinical outcomes including hepatic encephalopathy support what we know about the importance of increasing and maintaining muscle mass in patients with cirrhosis."¹

References

1. Lipocine Announces Positive Week 52 Results from LPCN 1148 Phase 2 Study in Patients with Cirrhosis. Lipocine Inc. News release. March 28, 2024. Accessed March 28, 2024. https://prnmedia.prnewswire.com/news-releases/lipocine-announces-positive-week-52-results-from-lpcn-1148-phase-2-study-in-patients-with-cirrhosis-302101966.html

2. LPCN 1148 Phase 2 Study Meets Primary Endpoint in Patients with Cirrhosis. Lipocine Inc. News release. July 27, 2023. Accessed March 28, 2024. https://www.prnewswire.com/news-releases/lpcn-1148-phase-2-study-meets-primary-endpoint-in-patients-with-cirrhosis-301886930.html

3. A Study to Assess the Efficacy, Safety, and Tolerability of Oral LPCN 1148 in Male Subjects With Cirrhosis of the Liver and Sarcopenia. ClinicalTrials.gov identifier: NCT04874350. Updated March 15, 2024. Accessed March 28, 2024. https://clinicaltrials.gov/study/NCT04874350