Lipocine's LPCN 1144 Met Non-Alcoholic Steatohepatitis ("NASH") Resolution Regulatory Endpoint in Phase 2 LiFT Study

Histological Analysis Demonstrates Treatment Potential of LPCN 1144 in NASH

- Both LPCN 1144 treatment arms met with statistical significance the pre-specified histology based regulatory endpoint of NASH resolution with no worsening of fibrosis

- Treatment effect observed on fibrosis improvement needs confirmation in a larger study

- Changes in key liver enzymes and body composition support beneficial treatment effects of LPCN 1144

- LPCN 1144 was well tolerated with an overall safety profile comparable to placebo

- Positive topline results support LPCN 1144 development for regulatory approval

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SALT LAKE CITY, Aug. 25, 2021 /PRNewswire/ -- Lipocine Inc. (NASDAQ: LPCN), a clinical-stage biopharmaceutical company focused on metabolic and endocrine disorders, today announced positive topline 36-week results from its Phase 2 proof of concept LiFT ("Liver Fat intervention with oral Testosterone") clinical study, NCT04134091, investigating LPCN 1144 in men with biopsy-confirmed NASH. Currently, there are no approved treatments for NASH, a leading cause of liver failure and liver transplantation globally. LPCN 1144 comprises an orally delivered prodrug of endogenous testosterone ("T").

The LiFT clinical study, a prospective, multi-center, randomized, double-blind, placebo-controlled, multi-arm, multi-site trial in the United States, enrolled biopsy-confirmed hypogonadal or eugonadal male NASH subjects with stage F1-F3 fibrosis and a NAFLD Activity Score ≥ 4 for a 36-week treatment period.   Subjects with advanced fibrosis (F2-F3) and steatohepatitis (inflammation on liver biopsy) were also eligible.  Subjects were randomized 1:1:1 to one of three arms (Treatment A, a twice daily oral dose of 142 mg testosterone equivalent; Treatment B, a twice daily oral dose of 142 mg testosterone equivalent formulated with 238 mg of d-alpha tocopherol equivalent; and the third arm, a twice daily matching placebo). 

The primary endpoint of the LiFT clinical study was change in hepatic fat fraction via MRI-PDFF post 12 weeks of treatment. Additionally, key secondary endpoints post 36 weeks of treatment include assessment of histological change for NASH resolution and/or fibrosis improvement. The LiFT clinical study was not powered to assess statistical significance of any of the secondary endpoints. 

At 12 weeks, treatments with LPCN 1144 resulted in statistically significant liver fat reduction, assessed by MRI-PDFF, meeting the pre-specific primary endpoint of the LiFT clinical study.  Statistically significant reduction in liver fat was observed compared to placebo: up to a mean of 9.2% absolute reduction and a 46.8% relative reduction in liver fat. 

Liver biopsies were performed at baseline ("BL") and after 36 weeks of treatment ("EOS"). Prespecified biopsy analyses include NASH Clinical Research Network ("CRN") scoring as well as a continuous paired ("Paired Technique") and digital technique ("Digital Technique-Fibronest").  All biopsy analyses were performed on the same slides and the reads for the three techniques were done independently. Analysis sets included the NASH Resolution Set (all subjects that have BL and EOS biopsy with NASH at BL [NAS ≥4 with lobular inflammation score ≥ 1 and hepatocyte ballooning score ≥1 at BL] (n=37)), the Biopsy Set (all subjects with baseline and EOS biopsies (n=44)), and the Safety Set (all randomized subjects (n=56)).  

Both LPCN 1144 treatment arms met with statistical significance the pre-specified accelerated approval regulatory endpoint of NASH resolution with no worsening of fibrosis based on NASH CRN scoring.  Additionally, both treatment arms showed substantial improvement of the observed NASH activity in steatosis, inflammation and ballooning.

Key results are presented in the following table:

Both LPCN 1144 treatment arms showed significant improvement in NASH without worsening of fibrosis using Paired Technique, which concurred with the NASH CRN scoring findings (per Biopsy Set; NASH Improvement responders: Placebo – 13%, Treatment A – 60%, Treatment B – 57%; NASH Improvement with No Worsening of Fibrosis responders:  Placebo – 13%, Treatment A – 60%, Treatment B – 57%). 

The treatment effects on fibrosis improvement need confirmation in a larger study.

Key fibrosis improvement results are presented in the following table:

In both treatment arms substantial reductions in markers of liver injury compared to placebo were observed post four weeks of treatment and were sustained through EOS.  Using all available Safety Set data, alanine aminotransferase ("ALT") decreased up to a mean of 23.4 U/L at EOS from all group mean baseline of 51.5 U/L and aspartate aminotransferase ("AST") decreased up to a mean of 13.3 U/L at EOS from all group mean baseline of 31.9 U/L.

Positive effects in appendicular lean mass and whole-body fat mass, an indicator overall tissue quality, based on dual-energy X-ray absorptiometry scans were noted in both LPCN 1144 treatment arms.

During the 36 weeks of treatment, LPCN 1144 was well tolerated with an overall safety profile comparable to placebo. Frequency and severity of treatment emergent adverse events, TEAEs, in both treatment arms were comparable to placebo. Study drug related TEAEs were mild to moderate. Four subjects discontinued due to TEAEs in the placebo arm vs one subject in total across the treatment arms. Cardiovascular events were balanced among groups with hematocrit increases averaging