Could a breast cancer candidate treat COVID-19? Polyphor's drug shows dual action in early studies

As scientists around the world continue to search for effective COVID-19 treatments, a Swiss biotech is stepping up to suggest that one of its clinical candidates, currently in late-stage development for breast cancer, may represent a relevant option.

The drug, called balixafortide, reduced viral load of SARS-CoV-2—the coronavirus that causes COVID—as well as COVID-related inflammation markers in hamsters, Swiss company Polyphor said.

The company is now considering starting a phase 2 proof-of-concept study to test the drug in patients with confirmed COVID-19 infections. Polyphor doesn’t anticipate any additional research requirements will be needed to launch the trial but will evaluate the feasibility from regulatory, strategic and operational standpoints, Polyphor CEO Gökhan Batur said via email.

Balixafortide is an inhibitor of CXCR4, the protein receptor for a member of the CXC chemokine family. It’s expressed on most immune cells and is known as an entry point that HIV uses to infect T cells. It is also over-expressed in multiple cancers and linked to tumor proliferation and growth.

In COVID-19, early evidence has pointed to increased activation of bystander CXCR4-expressing T cells in the lungs as a contributor to the worsening of symptoms.

Polyphor tested the drug’s activity against SARS-CoV-2 in cell cultures in collaboration with the University of Basel. Under an assay that evaluates the protection of cells against viral infection, the drug showed “a clear effect … which was different from” Gilead Sciences’ FDA-approved Veklury (remdesivir), the company described in a statement.

Encouraged by the findings in cell cultures, the company worked with academic institutions on animal tests. In hamsters, balixafortide also showed a statistically significant reduction of coronavirus viral load.

Inflammation associated with SARS-CoV-2 infection is a key driver of COVID severity. In the hamster study, the researchers noted balixafortide reduced several inflammation markers in the lung, including the expression of the ISG15 gene, which is involved in respiratory failure during viral infections, according to Polyphor.

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Balixafortide is the latest example of an existing med being repurposed for COVID-19, as scientists try to improve upon the efficacy seen with Veklury and anti-coronavirus antibodies from the likes of Eli Lilly and Regeneron.

A group of scientists at the Chinese Academy of Sciences’ Shenzhen Institutes of Advanced Technology recently found that Acrotech Biopharma’s lymphoma drug Folotyn (pralatrexate) inhibited SARS-CoV-2 more strongly than remdesivir did in a hybrid of computational models.

Another study by researchers from the Icahn School of Medicine at Mount Sinai and the University of California, San Francisco pointed to Spanish company PharmaMar’s plitidepsin—approved in some countries as a multiple myeloma treatment—as a more potent coronavirus killer than remdesivir in cell cultures.

As Polyphor considers testing balixafortide in COVID-19, it is nearing a readout from a phase 3 clinical trial dubbed FORTRESS, which is testing the med in combination with Eisai’s Halaven (eribulin) in patients with metastatic HER2-negative breast cancer.