Lipocine announced top-line results from the 16-week Liver Fat Imaging Study ("Liver Fat Study") with LPCN 1144. The Liver Fat Study was designed to assess the therapeutic potential of LPCN 1144 in non-alcoholic steatohepatitis ("NASH") with liver fat changes assessed using magnetic resonance imaging, proton density fat fraction ("MRI-PDFF") technique, a non-invasive quantitative biomarker of liver fat content. NASH is an advanced form of non-alcoholic fatty liver disease ("NAFLD") and occurs when fat accumulates in liver cells due to causes other than excessive alcohol use and a patient has hepatitis (inflammation of the liver) and liver cell damage. Currently there are no approved treatments for NASH. NASH is a silent killer that affects ~30 million Americans.
The Liver Fat Study was an open-label, multi-center, single arm study evaluating 16-week LPCN 1144 treatment in a cohort of 36 hypogonadal males. There were 34 evaluable subjects that had at least one post-baseline MRI-PDFF visit. Sixty-two percent (62%) of the evaluated subjects had NAFLD, defined as baseline liver fat of at least 5%.
Treatment results at End of Study ("EOS") with LPCN 1144 demonstrated that 48% of the treated NAFLD subjects had NAFLD resolution, defined as liver fat <5% post treatment, an improvement over the 28% percent observed after ~8 weeks of treatment. Additionally, 100% subjects experiencing NAFLD resolution had at least a 35% relative liver fat reduction from baseline with a relative mean liver fat reduction of 55% in this group.
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"The results from the Liver Fat Study are striking because both the proportion and degree of improvement in steatosis rivals or exceeds those seen with other drugs currently in development. Furthermore, the extent of NAFLD resolution provides a strong rationale for additional studies in both hypogonadal males with NASH as well as more unselected populations of men with NASH," said Dr. Arun Sanyal, Professor in the Virginia Commonwealth University (VCU) Department of Internal Medicine and Education Core Director in the VCU Center for Clinical and Translational Research.
Reportedly, sarcopenia, skeletal fragility, sexual/mood disorder, and anemia, all symptoms of low testosterone, are strongly associated with liver disease, likely due to compromised androgen signaling. Testosterone deficiency is also known to further exacerbate liver disease symptoms.
"We are encouraged by the Liver Fat Study results, especially the extent of the observed NAFLD resolution which improved over eight-week interim results with potential for further improvement upon longer treatment," said Dr. Mahesh Patel, Chairman, President and Chief Executive Officer of Lipocine. Dr. Patel further stated, "We look forward to conducting further clinical testing with LPCN 1144, in biopsy confirmed NASH subjects."
NASH is a more advanced state of NAFLD and can progress to a cirrhotic liver and eventually hepatocellular carcinoma or liver cancer. Twenty to thirty percent of the U.S. population is estimated to suffer from NAFLD and fifteen to twenty percent of this group progress to NASH, which is a substantially large population that lacks effective therapy. NAFLD/NASH is becoming more common due to its strong correlation with obesity and metabolic syndrome, including components of metabolic syndrome such as diabetes, cardiovascular disease and high blood pressure. In men, especially with comorbidities associated with NAFLD/NASH, testosterone deficiency has been associated with an increased accumulation of visceral adipose tissue and insulin resistance, which are factors contributing to NAFLD/NASH.
LPCN 1144 is a product targeted for treatment of pre-cirrhotic NASH comprising an oral prodrug of bioidentical testosterone, an androgen receptor agonist. Based on the multiple clinical studies with up to 52-week exposure, LPCN 1144 is well tolerated, exhibited no adverse drug reaction in the Hepatobilliary System Organ Class (e.g., peliosis hepatitis, hepatic neoplasms, cholestatic hepatitis and jaundice), exhibited no observed increase in mean LDL, exhibited no increase in mean serum hormone binding globulin ("SHBG"), exhibited no deaths or MACE events, and exhibited no drug related SAEs. Moreover, LPCN 1144 has shown good gastrointestinal tolerability with no signs of skeletal fragility (adverse muscle mass or bone density effects) or nephrotoxicity. LPCN 1144 recently completed a proof-of-concept clinical study demonstrating the potential utility in treatment of NASH. The U.S. Food & Drug Administration ("FDA") has indicated that a Phase 2 clinical study of LPCN 1144 in NASH with biopsy confirmed NASH subjects may proceed.