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Our Science
Anthracyclines have been the most widely used and most effective category of cancer chemotherapeutics for decades, however efficacy comes with serious toxicity. Patients are limited to strict lifetime limits of anthracycline doses to reduce the risk of permanent and irreversible damage to the cardiovascular system.
Bisantrene is a small-molecule anthracene that was originally developed by Lederle Laboratories (American Cyanamid) in the 1970s & 1980s with the goal of creating an alternative chemotherapeutic with a lower risk of cardiotoxicity.
The drug was approved in France for relapsed or refractory (R/R) acute myeloid leukemia (AML) in 1988, however it was not commercialised due to clinical prioritisation of mitoxantrone by Lederle.
Bisantrene has been evaluated in over 50 clinical trials with more than 1,500 patients treated, demonstrating efficacy and a well characterised safety profile.
Studies have shown bisantrene is an effective anticancer chemotherapeutic and lower cardiotoxicity than currently used anthracyclines. Recent preclinical studies have discovered that bisantrene is not only less cardiotoxic than anthracyclines, but when used in combination is able to protect hearts from anthracycline cardiotoxicity while also improving targeting of the cancer.
Reformulated bisantrene – RC220
One of the major factors contributing to Lederle abandoning clinical development of bisantrene in favour of the related anthracene chemotherapeutic mitoxantrone was the inability to deliver bisantrene via peripheral infusion. Rapid crystallisation of bisantrene at pH above 6 required that bisantrene be delivered by an invasive central line catheter. This restricted the use of bisantrene to hospital environments and cancer indications where central line administration is standard such as high intensity chemotherapy in leukaemias despite trying to reformulate the drug to improve its solubility.
Race has developed a novel formulation of bisantrene (RC220) designed to allow administration via a peripheral vein while maintaining the pharmacokinetics and anticancer activity of the historical formulation (RC110). cGMP manufacturing of RC220 was completed at Ardena in Q1 2024.
Bisantrene shows potent cell-killing activity against a diverse range of human cancers.
Figure 1. Bisantrene shows broad anti-cancer activity. The half-maximal inhibitory concentration (IC50) was determined for bisantrene against 143 cancer cell lines derived from diverse human tumour types. Boxes show the 25%-75% range, with the line within each box representing the median IC50 value. The upper and lower edges of the box represent the 75th and 25th percentiles, respectively. Whiskers show the minimum and maximum IC50 values observed for each cancer cell type.
Bisantrene significantly improves the cancer cell killing activity of doxorubicin
Figure 2. Combining bisantrene with doxorubicin increases cell-killing activity. Proportion of cell lines showing improved (i.e. lower) IC50 values when comparing doxorubicin + bisantrene treatments to doxorubicin alone. A significant difference was observed for the median IC50 of cells treated with doxorubicin + bisantrene when compared to doxorubicin alone, p<0.0001. Statistical analysis was performed using the non-parametric Wilcoxon matched-pairs signed rank test.
Bisantrene protects the hearts of mice from permanent damage caused by the anthracycline doxorubicin
Heart protection was achieved using higher levels of chemotherapy treatment with no extra toxicity observed
Heart protection was achieved using higher levels of chemotherapy treatment with no extra toxicity observed
Data supports using bisantrene with anthracyclines to protect the hearts of patients from chemotherapy
Promise of better cancer treatment with less side effects
Promise of better cancer treatment with less side effects