Galmed To Design Phase III NASH Trial With FDA After Strong Aramchol Data
Executive Summary
The Israel-based biopharma company said a Phase IIb trial of its oral treatment of non-alcoholic steatohepatitis hit the necessary endpoints to support a Phase III trial and FDA marketing application.
Galmed Pharmaceuticals Ltd. said it will soon enter talks with the US FDA on designing a Phase III trial of its liver-targeted SCD1 modulator Aramchol for treating non-alcoholic steatohepatitis (NASH) after positive Phase IIb top-line data showed it met the necessary endpoints.
The NASDAQ-listed Israeli company said the Phase IIb ARREST study of its lead drug candidate supported a pivotal trial and an FDA marketing application after the once-daily treatment for NASH produced positive top-line, 52-week results.
ARREST tested Aramchol (arachidyl amido cholanoic acid) in 247 patients with biopsy-proven, advanced NASH who were also overweight or obese and had prediabetes or type 2 diabetes. Top-line results from the study showed a statistically significant reduction in liver fat by magnetic resonance spectroscopy with its Aramchol 400mg versus placebo.
Importantly, significantly more patients treated with Aramchol 600mg versus placebo showed NASH resolution without worsening of fibrosis in the 52-week biopsy – an approvable endpoint.
Pivotal Phase III NASH Trial Next
"We are excited with the ARREST trial results that will enable Galmed to meet with the regulators as soon as possible and discuss the pivotal study design," Galmed Chief Executive Allen Baharaff told analysts on June 12 when announcing the trial's results. Aramchol has FDA fast track status for treating NASH.
Galmed said that results for the ARREST's two biopsy endpoints – which may currently constitute a primary endpoint for a Phase III trial to support an FDA marketing application – demonstrated two key things: First, concerning the two biopsy-based endpoints for NASH and for patients on 600mg Aramchol, a number of them achieved NASH resolution without worsening of fibrosis. Also, a greater proportion of them experienced stable NASH and improved their fibrosis score.
Most Analysts Applaud ARREST
Analysts at LifeSci Capital said that while liver fat content was an important consideration given it ultimately drives disease, the approvable FDA endpoints are either resolution of NASH without worsening of fibrosis, or at least one point improvement in fibrosis without worsening of NASH.
"Galmed’s data on NASH resolution without worsening of fibrosis were impressive," they concluded in a reaction note.
Galmed will now conduct a complete analysis of the ARREST data in preparation for a meeting with the FDA to determine the design of a subsequent Phase III study.
Analysts said a likely timeline is for a pivotal Phase III trial to begin in early Q1 of 2019.
Biotech analysts at H.C. Wainwright said that "long considered a steatosis-specific dark horse in the overall NASH field, Aramchol has now established, we believe, positive dose-dependent results," adding that the ARREST data was "unequivocally positive."
Datamonitor Healthcare analyst John Allen struck a cautious note, however, telling Scrip that "while it was positive to see that the treatment did result in a greater number of patients experiencing NASH resolution, I suspect based on some of the other data presented - most notably the MRS (Magnetic Resonance Spectroscopy) liver fat data, the individual responses in the trial were likely highly variable. As such while there results were positive I am cautious to say they are overwhelming."
News of the ARREST trial results sent Galmed's share price soaring. That market response was in sharp contrast to that in mid-February when panic selling of the biotech's shares followed news its ARRIVE proof-of-concept Phase IIa clinical trial of Aramchol in treating patients with HIV and non-alcoholic fatty liver disease (NAFLD) had failed to meet the primary endpoint of an improvement of liver fat at 12 weeks, due to poor trial design.
NASH is an emerging health crisis impacting an estimated 3% to 5% of the US population and an estimated 2% to 4% globally. It is the fastest growing cause of liver cancer and liver transplant in the US owing to the rise in obesity.
The disease, which is characterized by an accumulation of fat in the liver that can lead to the development of fibroids and eventually cirrhosis, currently has no treatments, but analysts estimate the market could be worth upwards of $10bn.
Aramchol is a novel fatty acid bile acid conjugate, inducing beneficial modulation of intra-hepatic lipid metabolism.
Aramchol’s ability to modulate hepatic lipid metabolism was discovered and validated in animal models, demonstrating downregulation of the three key pathologies of NASH: steatosis, inflammation and fibrosis. The effect of Aramchol on fibrosis is mediated by down-regulation of steatosis and directly on human collagen producing cells.