Galectin Therapeutics (Nasdaq:GALT), the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, announces details of the design of its Phase 2 program with GR-MD-02 in patients with advanced fatty liver disease, or nonalcoholic steatohepatitis (NASH) with cirrhosis.
The program includes two clinical studies. The first is a multicenter, randomized, placebo-controlled, double-blind, parallel-group Phase 2 trial to evaluate the safety and efficacy of GR-MD-02 for the treatment of liver fibrosis and resultant portal hypertension in patients with NASH cirrhosis (the NASH-CX trial). This trial is expected to commence in the second quarter of 2015 with data readout expected in the fourth quarter of 2017. In addition, the Company will conduct a smaller trial of shorter duration in NASH patients with advanced fibrosis (the NASH-FX trial).
The NASH-CX trial was designed with guidance from the U.S. Food and Drug Administration (FDA) received during an End-of-Phase 1 meeting. The NASH-CX trial will include 45 sites (and up to 60 sites, if necessary) in the U.S. and Canada and will enroll a total of 156 patients. It will be comprised of three parallel treatment arms of 52 patients each, with one arm receiving 8 mg/kg of GR-MD-02, the expected therapeutic dose, one arm receiving 2 mg/kg of GR-MD-02 and a third arm receiving placebo. Patients will receive a total of 26 infusions every other week for one year and will be evaluated to determine the change in the hepatic venous pressure gradient (HVPG) as compared with placebo.
The FDA has indicated that HVPG may serve as a surrogate primary endpoint for NASH cirrhosis. HVPG will be correlated with secondary endpoints of fibrosis on liver biopsy as well as with measurement of liver stiffness (FibroScan®) and assessment of liver metabolism (13C-methacetin breath test, Exalenz), which are non-invasive measures of the liver that may be used in future studies.
Galectin is finalizing a submission to the FDA by the end of February for a Special Protocol Assessment (SPA) to accept this trial, if positive, as one of the required trials to support approval of the drug candidate. The FDA has previously agreed to review this study protocol for acceptance under an SPA.
Peter G. Traber, M.D., Galectin’s chief executive officer, president and chief medical officer, said, “We are very excited to begin testing our drug candidate in a larger patient population, and we look forward to working with PPD, our contract research organization. There are no approved drugs to treat NASH, and fatty liver disease and NASH are stealth diseases that advance from early stages through to advanced disease without symptoms. When symptoms of any significance do occur, the disease is already full-blown cirrhosis of the liver and the damage is currently considered to be irreversible and the treatment is liver transplant. We are hopeful that GR-MD-02 will prove to be a solution to this significant health problem. As many as 28 million Americans are afflicted with NASH, of which up to 6 million have advanced fibrosis.”
Dr. Traber added, “Our successful Phase 1 program showed GR-MD-02 to be safe and well-tolerated, and reached the targeted therapeutic range in the 8 mg/kg dose cohort. Patients in this group showed encouraging effects on a relevant biomarker of fibrotic liver disease and a potential signal indicating a reduction in liver stiffness. These findings are even more notable in light of the short, four-dose treatment regimen tested.”
The NASH-FX trial is a 30-patient, randomized, placebo-controlled, blinded study to be conducted at Brooke Army Medical Center with enrollment expected to begin in mid-2015. Patients with NASH with advanced fibrosis will be randomized with 20 receiving 8 mg/kg GR-MD-02 and 10 receiving placebo every other week for 16 weeks, for a total of nine doses. Following the treatment period, the safety and the efficacy of GR-MD-02 on liver stiffness will be evaluated as assessed by magnetic resonance-elastography and FibroScan score, and on imaging of liver fibrosis using multi-parametric magnetic resonance imaging (LiverMultiScan®, Perspectum Diagnostics). Top-line data is expected to be available in mid-2016.
“We believe that this smaller study will provide important information that could inform future larger trials that ultimately may widen the target market for GR-MD-02,” continued Dr. Traber. “This study will evaluate three promising non-invasive tests for assessment of liver fibrosis, while offering shorter treatment in a population of patients with advanced fibrosis, but not necessarily cirrhosis.”
More details on the clinical trials can be found in Galectin’s Corporate Presentation on our website, www.galectintherapeutics.com. Galectin anticipates that the cost of completing both studies will be approximately $20 million over the two and one-half year duration of the trials. As of December 31, 2014, Galectin had cash and cash equivalents of $29.1 million.
GR-MD-02 is a complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of fatty liver disease and fibrosis. Galectin-3 plays a major role in diseases that involve scaring of organs including fibrotic disorders of the liver, lung, kidney, heart and vascular system. The drug binds to galectin proteins and disrupts their function. Preclinical data in animals have shown that GR-MD-02 has robust treatment effects in reversing liver fibrosis and cirrhosis.
About Fatty Liver Disease with Advanced Fibrosis and Cirrhosis
Non-alcoholic steatohepatitis (NASH), also known as fatty liver disease, has become a common disease of the liver with the rise in obesity rates. NASH is estimated to affect up to 28 million people in the U.S. Fatty liver disease is characterized by the presence of fat in the liver along with inflammation and damage in people who consume little or no alcohol. Over time, patients with fatty liver disease can develop fibrosis, or scarring of the liver, and it is estimated that as many as 1-2 million individuals will in the U.S. have cirrhosis, a severe liver disease for which liver transplantation is the only treatment available. Approximately 6,300 liver transplants are performed annually in the U.S. There are no drug therapies approved for the treatment of liver fibrosis.
Shares of Galectin Therapeutics (GALT) closed yesterday at $3.81 . GALT has a 1-year high of $19.11 and a 1-year low of $3. The stock’s 50-day moving average is $3.57 and it’s 200-day moving average is $4.45.
On the ratings front, Galectin Therapeutics has been the subject of a number of recent research reports. In a report issued on January 6, MLV & Co. analyst Vernon Bernardino maintained a Buy rating on GALT, with a price target of $16, which represents a potential upside of 319.9% from where the stock is currently trading.
Galectin Therapeutics Incis a development-stage company engaged in drug research and development to create new therapies for fibrotic disease and cancer.