Tackling NASH cirrhosis
Galectin Therapeutics is one of the only biotech companies with an active Phase IIb/III clinical trial for NASH cirrhosis. Galectin recently launched a site dedicated to its study, NAVIGATE: https://navigatenash.com/. Also, the Journal for ImmunoTherapy of Cancer recently published Phase I clinical research showing belapectin, Galectin Therapeutics’ galectin-3 inhibitor, enhances tumor response in combination with anti-PD-1 therapy. Med Ad News discussed these and other topics with Dr. Pol Boudes, CMO of Galectin.
Med Ad News: Please discuss the effects of NASH cirrhosis in the United States and belapectin’s potential impact in the marketplace if approved by the U.S. FDA.
Dr. Pol Boudes: Cirrhosis prevalence in US is estimated at 2 million individuals and at 3 million in Europe. NASH is now the main etiology for liver cirrhosis and its incidence and prevalence are predicted to grow dramatically. NASH is already estimated to be the number one reason for liver transplantation in the developed world. Currently, apart from a liver transplantation, these patients have very limited options. These options are at best palliative, meaning that any treatment that can alter the progression of cirrhosis would represent a medical breakthrough in a field that has been neglected for many, many years. The belapectin program is innovative in multiple ways, notably in terms of clinical research, the science surrounding galectin-3, the mechanism of action of belapectin to inhibit galectin-3, and the clinical study design that could lead to registration of the drug.
Med Ad News: How does the new website educate patients and physicians about liver cirrhosis resulting from NASH as well as support the NAVIGATE study?
Dr. Pol Boudes: We used lay language directed at patients and their families to explain what liver cirrhosis is. For instance, cirrhosis is not a term that is part of daily conversation. It is still a technical term, and, if someone has heard of cirrhosis, it is associated with alcoholism, a negative connotation. We need to change that. The most frequent reason for having liver cirrhosis in our country today is not related to alcoholism, but to obesity.
For physicians – particularly if they are not hepatologists or gastroenterologists – we explain how simple clinical markers should raise the suspicion of cirrhosis. These markers are nearly as good as more sophisticated, and expensive, tests that are not available to family practitioners. These simple markers will help physicians, such as family practitioners, to refer their patients to the appropriate specialist. NAFLD and NASH are so prevalent that family practitioners have such patients in their consultations but do not always think about liver health, notably because these patients have more immediately evident needs, such as controlling their cardiovascular risk, their weight, or their diabetes. Cirrhosis can remain asymptomatic for many years until, all of a sudden, it decompensates, and it’s unfortunately too late to do anything but a liver transplantation, an option that is unavailable to many. So the sooner you intervene, the better.
Med Ad News: Please discuss how belapectin in combination with pembrolizumab significantly enhances tumor response to immunotherapy in patients with advanced metastatic melanoma and head & neck squamous cell carcinoma.
Dr. Pol Boudes: Based on animal model data and study in patients with refractory cancers, such as melanoma or head and neck cancers, we can explain the contribution of belapectin. Belapectin modifies the tumor micro environment by diminishing the activity of monocytes and macrophages with a resulting increased activity in lymphocytes that kills tumor cells. Basically, belapectin creates a micro environment that restores or boosts the activity of pembrolizumab. Another consequence, which we cannot explain scientifically right now, is that the combination of belapectin and pembrolizumab appears to be better tolerated than pembrolizumab alone. This is important because better tolerance means that pembrolizumab could be given for a longer period of time and at the appropriate efficacious dose, which ultimately should result in a better clinical outcome for patients.
Med Ad News: What promising clinical results has belapectin demonstrated in other therapeutic areas?
Dr. Pol Boudes: Apart from liver cirrhosis and metastatic cancers, we collected very intriguing efficacy data in psoriasis. A patient who had both a hepatic disease and a challenging psoriasis saw the latter cleared, unexpectedly. This led to a small clinical trial in psoriasis patients that confirmed this efficacy signal. The program was not pursued because so many options are now available to patients with psoriasis. However, these data support the involvement of galectin-3 in many inflammatory diseases and the potential that its inhibitory action represents for additional indications beyond liver cirrhosis and metastatic cancers.