Galectin Therapeutics takes its role seriously, as perhaps the only company developing a therapy for non-alcoholic steatohepatitis (NASH) cirrhosis, an advanced form of NASH. Along with its Phase IIb/III clinical trial, it recently launched NAVIGATEnash.com.
Galectin Therapeutics takes its role seriously, as perhaps the only company developing a therapy for non-alcoholic steatohepatitis (NASH) cirrhosis, an advanced form of NASH. Along with its Phase IIb/III clinical trial, it recently launched NAVIGATEnash.com.
This new website is designed to share insights from and among physicians involved in Galectin’s clinical trials, and to educate patients about this advanced form of the disease.
The problem the website will help solve is that, “Physicians often don’t recognize NASH and NASH cirrhosis, and patients don’t know they have it,” Pol Boudes, M.D., chief medical officer for Galectin Therapeutics, told BioSpace. NAVIGATEnash.com, therefore, has two educational prongs.
One prong educates physicians and patients about the disease, diagnostic tests and treatments.
The other prong focuses on registered users – the physicians and nurses treating patients in the NAVIGATE trial.
“The clinical trial is doing something never done before, and we’re learning from each exchange. The only treatment available for NASH cirrhosis is a liver transplant,” so capturing and leveraging each insight is very important.
“Most researchers are focused on the early stages of NASH, before cirrhosis,” he said. “Cirrhosis of the liver has always been neglected. People don’t like to talk about it, even when it’s not associated with alcoholism.”
The stigma is so great that another liver disease, primary biliary cirrhosis, was given a separate name: primary biliary cholangitis.
So far, there is no approved treatment to stop the progression and more serious complications of NASH cirrhosis.
“Cirrhosis can be silent for years. There are ways to detect it, but they often are overlooked,” Boudes said.
With no effective drug therapy, liver transplants are the only treatment option for advanced patients.
Galectin hopes to change that. It is developing the first potential therapy specifically targeting NASH cirrhosis: belapectin – a galectin-3 inhibitor that is in the Phase IIb/III NAVIGATE clinical trial now.
With these advanced forms of the disease, “it’s a problem to find the right drugs,” Boudes said. Normally, the liver metabolizes any drugs given as therapies and excretes them in the bile or blood to be eliminated through kidneys into urine. “With cirrhosis, this capability decreases, so the treatments create side-effects.”
Galectin’s lead compound, belapectin, appears to largely solve that challenge as, Boudes said, “being a polycarbohydrate molecule, it appears to be very well tolerated. Galectin-3 is the molecule that fosters inflammation, which fosters fibrosis, which leads to cirrhosis in NASH.”
Belapectin binds to galectin-3, disrupting its function and possibly preventing NASH from developing into NASH cirrhosis.
Preclinical data suggests it may reverse liver fibrosis and cirrhosis and clinical data suggests it can prevent complication of cirrhosis. The company is enrolling a Phase IIb/III study now to determine its ability to prevent esophageal varices in NASH cirrhosis.
“We have a small, but significant, program in oncology, too,” Boudes said.
In cancer, galectin-3 fosters inflammation in the tumor microenvironment, thus preventing cells of the immune system from attacking cancer cells.
A Phase I study combining belapectin and pembrolizumab (Keytruda®) for advanced melanoma and head and neck cancer is underway.
“It appears to work well and be well tolerated compared to the side-effects you see with standard chemotherapy,” he said.
A paper published recently in the peer-reviewed Journal for ImmunoTherapy of Cancer provides proof-of-concept evidence that administering belapectin in combination with Keytruda® – a PD-1 inhibitor – significantly enhances tumor response in the target populations. It also offers the possibility of enhancing the safety and tolerance of immunotherapy.
In that study, an objective response was seen in 50% of the metastatic melanoma patients and 33% of the head and neck cancer patients. Patients who responded to the therapy had reduced levels of monocytic myeloid-derived suppressor cells and increased numbers of effector memory T-cell than non-responders. The group that received the combination therapy experienced fewer immune-mediated adverse events than would be expected for patients taking Keytruda® alone.
While cancer and NASH initially appear quite different, “The common theme among these programs is the science,” he explained. “When you block galectin-3 in cirrhosis, you decrease inflammation and fibrosis. When you block galectin-3 in cancer, you modify the tumor microenvironment, creating a microenvironment in which the body’s own defense mechanisms can attack and destroy the cancer cells.”
Belapectin has the potential to address multiple indications – including other fibrotic diseases – involving galectin-3.
“We are exploring multiple possibilities,” Boudes added.
The next step for the NASH cirrhosis therapy, Boudes said, is to complete enrollment on the NAVIGATE trial.
“If the safety is as good as we have seen so far and the efficacy is confirmed, we can shoot for conditional approval of belapectin,” he said. “The risk/benefit ratio could be overwhelming.”
We should have an answer on which direction to take around the end of 2023.
As a cancer therapy, Galectin plans to conduct a Phase II study. For that, he said, “It would be nice to have partners.”
