Galmed Pharmaceuticals Ltd. reported full results from the Open-Label Part of the ARMOR study corroborating effects of Aramchol across all efficacy parameters. The study enrolled 157 subjects with biopsy-proven NASH randomized 1:1:1 into three groups differing in the timing of the post-baseline liver biopsy (Week 24, Week 48, and Week 72). Fifty-one (51) subjects underwent post-baseline biopsies prior to study discontinuation (28 subjects at <48 weeks and 23 subjects at =48 weeks).

The study was designed to assess the safety, pharmacokinetics (PK) and efficacy kinetics as a function of treatment duration. Three independent pathologists and three different histopathology reading methodologies were used to assess the antifibrotic effect of Aramchol: fibrosis stage based on NASH CRN; ranked assessment (improvement/worsening/stable) of paired (pre- and post-baseline) biopsies, blinded to sequence; and an automated and continuous score of Fibrosis Composite Severity (FCS), using FibroNest™, a quantitative AI digital pathology image analysis method. Noninvasive tests (NITs) included imaging (fibroscan) and biomarkers (liver enzymes, FIB-4, Pro-C3 and ELF).

Aramchol treatment resulted in a high proportion of subjects showing fibrosis improvement based on all three biopsy reading methodologies, with a larger treatment effect with longer duration of therapy. Following a treatment duration of 48 weeks or more, improvement in fibrosis was demonstrated in 39% of subjects according to NASH CRN and 61% of subjects according to ranked assessment. At Week 48 AI demonstrated fibrosis improvement in 100% of subjects when responders were defined by an absolute reduction of the FCS score >0.3, 65% when responders were defined by a relative reduction of >25%, and a statistically significant reduction from baseline in mean FCS score (p<0.0001).

NASH resolution without worsening of fibrosis was demonstrated in 26.5% of subjects. Fibroscan, ALT, AST, and FIB4 were analyzed using MMRM, based on all subjects (N=154). Fibroscan results were consistent, with an improvement in fibrosis showing a mean absolute reduction from baseline to week 72 of 2.5 kPa (p<0.0001).

At Week 72, ALT was reduced by 22 U/L (p<0.0001), AST was reduced by 18 U/L (p<0.0001), and FIB-4 was reduced by 0.30 (p<0.0001). Pro-C3 and ELF were analyzed for 43 subjects at week 24 showing reduction in both Pro-C3 levels (p<0.0001) and ELF (p=0.0038). The Open Label part demonstrated the good safety profile of Aramchol 300mg BID including long-term follow up.

The incidence of serious adverse events (SAEs) was consistent with the population (10.4%) and early discontinuation rates due to adverse events (AEs) were low (4.5%). ARMOR is a Phase 3 study comprised of two-parts, an open-label part and a randomized, double-controlled, placebo part, designed to evaluate the safety and efficacy of Aramchol in approximately 200 sites in the U.S., Europe and Latin America. The first part, an open-label study, was designed to evaluate treatment response kinetics, pharmacokinetics and safety of twice daily administration of Aramchol 300mg (new dosing regimen with higher exposure) in approximately 150 subjects with NASH and liver fibrosis stage 1-3 (F1 capped at 30 subjects).

Patients were randomized (1:1:1) into three groups with post-baseline liver biopsy being performed at 24 weeks, 48 weeks, or 72 weeks, respectively. In May 2022, the Company concluded that the Open-Label part of the study met its objective and discontinued the Open-Label part. The second part, a randomized, double-blind, placebo-controlled study, is designed to evaluate the safety and efficacy of Aramchol Meglumine to support regulatory approval, with both a histology-based phase and a clinically based phase.

As currently designed, a total of 2000 subjects with NASH and liver fibrosis stage 2 and 3 who are overweight and are either pre-diabetic or have type 2 diabetes are expected to be randomized 2:1 to receive Aramchol Meglumine or matching placebo. In the histology-based phase, the company intend to treat 1000 subjects with Aramchol or matching placebo for 72 weeks until the second biopsy. The histology-based data is intended to serve as the basis for the submission of a Sub-part H marketing authorization application under regulatory provisions of accelerated/conditional approval.

Following the discontinuation of the Open-Label Part of the ARMOR Study, the Company has no current plans to initiate the Double-Blind part of the ARMOR Study, the commencement of which depends on the outcome of its evaluation of strategic alternatives.