Written by Peter G. Traber, M.D. on September 9, 2015

An important question in drug development, and the subject of U.S. Food and Drug Administration (FDA) regulations, is whether a drug candidate interacts with other medications the target patient population may also be taking. This is a critical issue, because many patients with chronic diseases are on multiple medications over long periods of time and may take other medications on an intermittent basis.

The basis of many drug-drug interactions is that the experimental new drug may use some of the same metabolic pathways that other drugs use. If this is the case, the new drug may inadvertently increase the levels of other drugs in the system, and thus alter their effect and increase their side effects. Prescribing physicians need to know about potential unfavorable interactions, if any, between an experimental new drug like GR-MD-02 and other drugs their patients may require.

In evaluating potential drug interactions, the first experiments with GR-MD-02 were done in test tubes and with cell cultures. Many metabolic pathways were evaluated in this way to determine whether there were potential interactions with GR-MD-02. Generally, the results of these experiments showed there was little to no risk of drug metabolism interactions with GR-MD-02, but the analysis of one particular metabolic enzyme, called CYP3A4, suggested there was small risk for interaction with other drugs. Therefore, the company agreed with the FDA to evaluate the possible interaction in humans of GR-MD-02 with a model drug for the CYP3A4 enzyme.  The model drug used was midazolam, which is known as Versed® and is widely used for mild, conscious sedation.

We designed, conducted, completed, disclosed publicly (see our press release dated May 14, 2015) and reported to the FDA results of a Phase 1 study in normal healthy volunteer subjects.  This study first tested drug levels of midazolam after a single intravenous (IV) dose, which served as a control. Midazolam was then administered again and drug levels were monitored following a single IV dose of GR-MD-02 (8 mg/kg) and following three weekly IV doses of GR-MD-02 (also 8 mg/kg). A total of 17 subjects completed the study, and all met the primary endpoint of no difference between midazolam levels when administered alone and in combination with single and multiple doses of GR-MD-02. Of note, 8 mg/kg of body weight of GR-MD-02 is the same dose we are testing in our current Phase 2 program in nonalcoholic steatohepatitis (NASH) patients with cirrhosis and with advanced fibrosis.

These Phase 1 results show that GR-MD-02 has no effect on the metabolism and serum levels of midazolam, and these results can be imputed to other drugs metabolized by CYP3A4 that are in common use. In fact, the CYP3A4 enzyme metabolizes about half of all the drugs currently on the market, according to published estimates. (Click here for more information on CYP3A4.)  With the successful completion of this study, the company does not anticipate further drug-drug interaction studies will be required.

So, what does this science mean for the development of GR-MD-02?  First, another 17 healthy individuals received up to three doses of GR-MD-02 without any significant adverse events, confirming the safety of the drug as seen in the first Phase 1 trial. Second, these findings allow patients on concomitant medications to be enrolled in our Phase 2 clinical trials with minimal concern for drug interactions, thus increasing the pool of potential patients that can be included in the trials. Finally, should GR-MD-02 receive marketing approval, patients and physicians will be less concerned our drug will interfere with other drugs they may be taking and we will not be faced with restrictive labeling regarding concomitant drug therapy. Therefore, successful completion of this drug interaction study in people checks another box in describing the underlying properties to support approval of GR-MD-02.

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. 

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