Lipocine (NASDAQ:LPCN) announced topline results from its non-alcoholic steatohepatitis (NASH) liver fat study demonstrating relative liver fat reduction of 55% in patients with non-alcoholic fatty liver disease (NAFLD) at its conclusion. The enrollment criteria for the study included hypogonadal men, which allowed some patients without NAFLD (5% or greater liver fat) to participate. The effort was a 16-week, open-label, multi-center, single arm study that enrolled 36 hypogonadal males, and yielded 34 evaluable subjects. 21 were both evaluable and were diagnosed with NAFLD.
Ten patients achieved NAFLD resolution at the end of the study and they exhibited a mean reduction in liver fat of 55%. 21 patients achieved a minimum of 33% relative liver fat reduction, equivalent to a 4.0 percentage point reduction. Additional detail is provided in the following exhibit. Eight patients with 10% or greater liver fat at the beginning of the study experienced a 40% relative and 8.2 percentage point reduction of liver fat at the end of the study. This was an improvement from interim results which included seven subjects with a 7.6 percentage point reduction. NAFLD resolution improved dramatically from the interim results at 8 weeks increasing from 28% to 48% of the 21 subjects measured at the end of the study.
View Exhibit I – Summary of Study Data
The results from the study are positive and compare favorably with other results such as those from Madrigal with a 36 to 42% reduction and Gilead with a 29% reduction for GS-0976 and Intercept with a 17% reduction. Results from Viking were in a similar range, with a decline of 58%. These studies examined slightly different populations for a variety of study durations which makes comparisons imperfect.
We note than one of the leading players in the NASH market and Phase III candidate selonsertib failed to achieve its primary endpoint in February, moderating the competitive environment in this therapeutic area with no approved treatment or cure.
One of the strong points for LPNC 1144 is its safety profile and its history of review in many human trials in hypogonadal men. Some competing candidates, such as Intercept’s obeticholic acid is associated with elevated LDL-C, Gilead’s GS-0976 reported pruritus, upper respiratory tract infection, headache and fatigue, NGM’s NGM313 saw headache, diarrhea, loose stools and elevated LDL-C. Lipocine’s product is a prodrug of a bio-identical hormone, with good gastrointestinal tolerability. The drug has demonstrated no adverse reaction in the Hepatobilliary System Organ Class, no mean increase in LDL, and no signs of skeletal fragility or nephrotoxicity.
In a recent presentation, Lipocine provides a summary of relative change in liver fat and absolute change (which we call percentage point change) in liver fat included below. While all of these studies are examining different populations over different durations and seeking a variety of endpoints with a variety of designs, comparing the efficacy on the relative and absolute numbers is helpful in understanding how the competitors stack up. The data below for Lipocine includes the interim data. The final data will change the study duration of LPCN 1144 to 16 weeks in both charts and increase the number of observations from 7 to 10. In the “Relative Change” exhibit -38% moves to -40% and in the “Absolute Change” exhibit, -7.6 percentage points moves to -8.2 percentage points.
View Exhibit II – Relative Change of MRI-PDFF1
View Exhibit III – Absolute Change of MRI-PDFF2
While the number of patients is small, the study does provide sufficiently strong data to support progressing to the next step. We anticipate a Phase II trial to be designed that will continue to measure liver fat reduction as a primary endpoint and also fibrosis in F2 and F3 patients. There are several non-invasive fibrosis markers that can be employed, including transforming growth factor-β (TGF-β), PRO-C3 and others.
While measured in a small population, we see this proof of concept clinical study as supportive of additional research. On January 24th, Lipocine filed an investigational new drug (IND) application to start a Phase II NASH trial in biopsy confirmed NASH subjects. We expect additional details from the company regarding trial design and funding in the near term. The NASH/NAFLD space is attractive, especially for LPCN 1144 given its safety profile and apparent benefits over competitors. For LPCN’s target population, we have discussed an addressable market of $13 to $22 billion in a previous article. We currently do not include a valuation component for LPCN 1144, but expect to add upon receipt of additional details and funding for the anticipated Phase II trial.
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1 LPCN 1144 (LFS Study Interim Results); NGM282 (Harrison et al., NASH-TAG 2018): VK-2809 (Press Release, Nov 2018); MGL-3196 (Corp ppt, Evercore ISI, Nov 2018); BMS986036 (Sanyal et al., NASH-TAG 2018); NGM313 (Shankar et al., AASLD 2018): GS 0976 (Press Release, Oct 2018); OCA (Middleton et al., Gastroenterology 2017).
2 LPCN 1144 (LFS Study Interim Results); NGM282 (Harrison et al., NASH-TAG 2018); VK-2809 (Press Release, Nov 2018); MGL-3196 (Corp ppt, Evercore ISI, Nov 2018); BMS986036 (Sanyal et al., NASH-TAG 2018); NGM313 (Shankar et al., AASLD 2018): GS 0976 (Press Release, Oct 2018); OCA (Middleton et al., Gastroenterology 2017).