Lipocine Inc. announced positive topline results from a Phase 2 clinical study of LPCN 1148. LPCN 1148 is an oral candidate under development for the clinical management of cirrhosis, specifically prevention of OHE recurrence and treatment of sarcopenia. LPCN 1148 is targeted to be a "First in Class" product candidate with a novel mechanism of action (MOA). Lipocine plans to meet with the FDA to discuss a development path to NDA filing.

This Phase 2 proof of concept study was a randomized placebo-controlled study in sarcopenic male patients with cirrhosis on the liver transplant waitlist. In Stage 1, 29 patients were randomized 1:1 to receive either LPCN 1148 or matching placebo for 24 weeks. At Week 24, the open-label extension Stage 2 of the study commenced.

During Stage 2, 8 participants who were on placebo in Stage 1 converted to LPCN 1148, and 11 participants who started the study on LPCN 1148 continued treatment with LPCN 1148. The study's primary endpoint was a change in L3-SMI at week 24. L3-SMI estimates whole body skeletal muscle mass.

SMI was analyzed at baseline, and Weeks 12, 24, 36, and 52. Key secondary endpoints included rates of hepatic encephalopathy and the safety/tolerability of LPCN 1148. All LPCN 1148-treated participants completed Week 24 (n=15), and 10 of 14 placebo participants completed Week 24.

During the initial 24 weeks, all LPCN 1148-treated participants had at least one evaluable post-baseline CT scan and are therefore part of the modified intent to treat (mITT) analysis; 10 placebo-treated participants had an evaluable post-baseline CT. As prespecified, L3-SMI analysis was performed on the mITT population (n=25), with the last evaluable post-baseline observation carried forward (LOCF). Of those participants on placebo in Stage 1, 6 out of 8 who went on to receive LPCN 1148 starting at Week 24 had evaluable CT scans in Stage 2. Participants who received LPCN 1148 during Stage 1 had a significant (p<0.01) increase in L3-SMI of 4.1 cm2/m2 (8.8%) at Week 24, the primary analysis timepoint, and this increase was maintained through the additional 28 weeks of the study (Week 52, 4.1 cm2/m2, 8.7%).

Placebo participants who began receiving LPCN 1148 saw a marked increase in SMI as early as 12 weeks after therapy initiation (Week 36, 7.4 cm2/m2, 15.1%), and this increase was maintained through Week 52 (8.1 cm2/m2, 16.7%). Recurrent OHE is defined as an event of OHE in a participant with a medical history of HE. Most (22/29, 76%) study participants had experienced HE prior to this study, and there were similar numbers of these participants in each study arm in both Stage 1 and Stage 2. Nearly all (21/22, 95%) participants with a history of HE were on therapy for HE at baseline and during the study (lactulose and/or rifaximin).

During Stage 1, LPCN 1148 treatment resulted in significantly (p<0.05) fewer cases of recurrent OHE (1 vs 6), a potential FDA-approvable endpoint. During the open-label Stage 2, there were two cases of OHE, one in a participant who was receiving LPCN 1148 since Day 1, and one who began receiving LPCN 1148 at Week 24. The average time to first OHE recurrence was longer with LPCN 1148 treatment, at 183 days compared to 35 days for placebo.