On June 12, 2024 Race Oncology Ltd (ASX:RAC, OTC:RAONF) reported that it has hit a new 12-month high on fielding some strong preclinical findings on the efficacy of lead asset bisantrene in treating multiple myeloma (Press release, Race Oncology, JUN 13, 2024, View Source [SID1234644290]).
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Dangerous blood cancer
Multiple myeloma is a dangerous blood cancer caused by uncontrolled proliferation of plasma cells, more common in men over 60. It accounts for 10% of blood cancers and has a 5-year survival rate of 55.6%.
Carfilzomib is an intravenous drug used for relapsed or refractory multiple myeloma, with known cardiotoxicity risks, particularly in patients with pre-existing heart conditions.
When carfilzomib is combined with bisantrene, preclinical studies showed that bisantrene slows disease progression and enhances the efficacy of carfilzomib, offering a potentially safer treatment option.
The studies, performed under contract by Labcorp USA, revealed that bisantrene, both as a single agent and in combination with the standard multiple myeloma treatment carfilzomib – under the trademark Kyprolis, Amgen – effectively slows disease progression in a mouse model.
Bisantrene demonstrated the ability to kill human multiple myeloma cells at clinically relevant concentrations in cell cultures and in mice.
In combination with carfilzomib, the drug showed enhanced activity, which points to a potentially more effective and less cardiotoxic treatment for multiple myeloma patients.
Carfilzomib, although effective, is known for its serious heart toxicity side effects, limiting its use in patients with elevated cardiac risk factors.
Protecting the human heart
In 2021, Race made the groundbreaking discovery that bisantrene can protect human heart muscle cells from carfilzomib’s toxicity.
The mouse model studies showed that bisantrene significantly slowed multiple myeloma disease progression, whereas carfilzomib alone, at the maximum tolerated dosage, showed no single-agent activity.
And the combination of bisantrene and carfilzomib was more effective than bisantrene alone, suggesting a synergistic effect that warrants further investigation as a safer treatment option for multiple myeloma patients.
Next steps
The company plans to conduct additional preclinical studies to investigate the cellular mechanisms responsible for the delayed progression of multiple myeloma and increased survival in mice treated with the bisantrene and carfilzomib combination.
It also aims to complete mouse models of carfilzomib-induced cardiotoxicity to confirm bisantrene’s cardioprotective properties and explore options for clinical studies to evaluate the combination as a more effective and safer treatment for multiple myeloma patients.
Race CEO Dr Daniel Tillett said: "It is always exciting to see the potential clinical utility of bisantrene grow.
"Carfilzomib is a highly active treatment for multiple myeloma but it comes with very serious cardiotoxicity risks.
"The potential for using bisantrene to not only better treat multiple myeloma, but also protect patients from the heart damage caused by carfilzomib, is worthy of further investigation."