Written by Peter G. Traber, M.D. on August 17, 2015

Galectin Therapeutics is developing a drug called GR-MD-02 which binds to and inhibits the galectin-3 protein which is important in the promotion of multiple types of disease including inflammation, fibrosis, and cancer. We have focused the use of this drug in a development program for potential treatment of patients with liver fibrosis, and specifically in those patients with NASH (non-alcoholic steatohepatitis) with advanced fibrosis or the most severe form of fibrosis, cirrhosis. There are currently no available therapies for liver fibrosis due to NASH.

A clinical development program includes a complex set of scientific experiments and human clinical trials that hopefully results in marketing approval of a drug for use in patients. One of the most important aspects of a clinical development program is specifying the indication, which guides all other decisions. In our case, we are focused on the treatment of NASH in two key target populations, NASH with cirrhosis, and NASH with advanced fibrosis, but not cirrhosis. The importance of the unmet medical need in these patients and the strength of the data from our preclinical studies with GR-MD-02 resulted in the FDA giving this development program Fast Track status. Our overall drug development program includes studies in all of the following areas:

• Pre-clinical (animal) studies to show efficacy in disease models
• Pre-clinical (animal) studies to evaluate for potential drug toxicity
• Pre-clinical (animal) studies to evaluate how the drug is distributed in the body, metabolized, and eliminated from the body
• Chemical development studies to characterize the structure and quality of the chemical or new molecular entity
• Process development studies to design and optimize the production processes
• Pharmaceutical or formulation development studies to design an appropriate form and route of administration for the final drug product
• Clinical Phase 1 studies to demonstrate safety in small numbers of healthy volunteers and patients with NASH with advanced fibrosis
• Clinical Phase 2 studies to establish efficacy and dose, as well as safety in the indicated patient population
• Clinical Phase 3 studies to confirm safety and efficacy for the intended marketing indication and target patient population

A great deal of work has already been completed on the development program for GR-MD-02. Pre-clinical animal studies have been completed that demonstrate efficacy in two different liver disease models and this work has been published in the peer-reviewed scientific literature (1, 2). Multiple studies have been done in animals to evaluate potential toxicity of GR-MD-02 and how the drug is handled in the body. Extensive work has been performed to establish the pharmaceutical quality of the drug and production processes. Several batches of consistent quality have been produced in accordance with FDA requirements for human use and administration. These studies provided the foundation for the FDA allowing us to move into human trials.

Human studies are divided into three phases. Phase 1 studies refer to the first human studies and are primarily to determine drug safety in a small number of patients, usually healthy volunteers. However, some Phase 1 trials are allowed to be performed in diseased patients in order to also evaluate whether the drug is having the intended effect. Phase 2 studies focus on evaluation of efficacy as well as safety of the drug in subjects with the target disease. This is the phase of clinical development when it is determined whether the drug doses studied may be effective in the disease indication. Phase 3 trials are larger studies that confirm the efficacy of the drug, evaluate safety in a larger patient population, and serve as the primary registration trials for marketing approval.

Galectin has completed two Phase 1 clinical trials, with one in NASH patients with advanced fibrosis and one in healthy volunteers. The Phase 1 trial in patients with NASH fibrosis was highly successful demonstrating safety, providing dosing information for phase 2, and showing an effect on markers of fibrosis. This will be the subject of its own “CEO Perspective” in the future. On the basis of these Phase 1 studies, Galectin has initiated two phase 2 clinical trials to evaluate the possible reversal of liver fibrosis in NASH, the most common form of liver disease. The NASH-CX trial will focus on reversal of fibrosis in the most severe form of fibrosis called cirrhosis and the NASH-FX trial will attempt to show reversal of advanced fibrosis in a pre-cirrhotic stage.

More information on Galectin’s clinical trials can be found at clinicaltrials.gov

• Phase 1 https://clinicaltrials.gov/ct2/show/NCT01899859?term=GR-MD-02&rank=2
• NASH-CX: https://clinicaltrials.gov/ct2/show/NCT02462967?term=GR-MD-02&rank=3
• NASH-FX: https://clinicaltrials.gov/ct2/show/NCT02421094?term=GR-MD-02&rank=4

These “CEO Perspectives” will be a regular feature of our communication activities and may contain forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events and use words such as “may”, “could”, “expect” and others. These statements include those regarding the hope that Galectin’s development program for GR-MD-02 will lead to the first therapy for the treatment of fatty liver disease with advanced fibrosis and cirrhosis. For a discussion of additional factors impacting Galectin’s business, see the Company’s Annual Report on Form 10-K for the year ended December 31, 2014, and subsequent filings with the SEC. You should not place undue reliance on forward-looking statements. Although subsequent events may cause its views to change, management disclaims any obligation to update forward-looking statements

Please look for future editions in which multiple aspects of our development programs for unmet medical needs will be addressed.

Reference List

1. Traber PG, Chou H, Zomer E, Hong F, Klyosov A, Fiel MI, et al. Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease. PLoS One 2013;8(10):e75361.
2. Traber PG, Zomer E. Therapy of experimental NASH and fibrosis with galectin inhibitors. PLoS One 2013;8(12):e83481.

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