Combining Race’s bisantrene with decitabine enhances cancer-cell killing abilities, study shows- Bisantrene and decitabine used together offer significantly improved cancer cell-killing across 143 tumour cell lines than either drug used alone
- Results support the use of decitabine in combination with bisantrene as a potential new treatment for many cancers, including solid tumours
- Bisantrene/decitabine combination to be explored in upcoming Phase 1/2 investigator-initiated AML clinical trial.
Speical Report:Clinical-stage biopharmaceutical companyRace Oncology has achieved a key milestone with the potential of its lead drug bisantrene showing improved efficacy with the standard of care drug decitabine in a broad range of cancers, opening partnering opportunities.
Race Oncology (ASX:RAC)says bisantrene and decitabine used together offer significantly improved cancer cell-killing across a broad panel of 143 tumour cell lines compared with either drug used alone.
The results from recent preclinical work performed under contract at Oncolines B.V. (Netherlands) support the use of decitabine in combination with bisantrene as a potential treatment for many cancers, including solid tumours such as lung, prostate, pancreas, breast, head, and neck cancer.
In the study bisantrene was screened in combination with decitabine for enhanced anticancer activity across a broad panel of 143 cancer cell lines, representative of solid and blood cancers originating from more than 20 different human tissues.
CEO Dr Daniel Tillett says decitabine is a nucleoside analogue drug used in the treatment of some blood cancers, such as myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), but it has not shown clinical efficacy in solid tumours.
“Decitabine is a standard of care drug that has been around since the 1960s but it’s only useful in haematological (blood) cancers so leukaemia was the only type of cancer it could use on,” he says.
“It’s a good drug and works well but it has never worked in solid tumours, which is the vast majority of cancers.”
However, in the latest study, Tillett says decitabine was found to work well with bisantrene across a comprehensive range of the most common human cancer types.
Combining decitabine with bisantrene at clinically relevant concentrations significantly enhanced cancer cell-killing, with 92% (131 out of 143) of the cell lines showing improvement.
“The two drugs together worked much better in these cancers,” Tillett says.
The new body of work ishighly supportive of resultsfrom the University of Newcastle in preclinical AML models using a combination of bisantrene and decitabine.
“We’ve shown in preclinical animal work the two drugs together are much more effective at killing cancers,” Tillett says.
“The same combination we’ve seen work well with haematological cancers and we’re about to run a Phase 1/2 trial on AML using the combination.”
“We look forward to testing this combination in humans and showing whether it has application outside of mice.”
At the heart of cancer care
Bisantrene, an anthracene-based chemotherapy, was initially created by Lederle Laboratories, a small French pharmaceutical firm, during the 1970s and 1980s.
Research confirms bisantrene’s ability to lower the risk of cardiotoxicity and provide cardio-protection when used in conjunction with anthracyclines, a group of drugs used in cancer treatment.
Although effective in patients and approved for treating acute myeloid leukaemia (AML) in France, bisantrene’s complex administration prevented commercialisation.
RAC has reformulated the drug to enable easy clinical use through standard infusion via arm or leg veins.
RAC is developing bisantrene to meet the significant unmet needs of patients across multiple oncology conditions, initially focusing on metastatic breast cancer and AML.
The biotech is exploring its anticancer and cardio-protective properties alongside known standards of care.
When tested against a panel of 143 cancer cell lines representing more than 20 human tumour types, bisantrene has previously been shown to kill more than 79% of the cells at clinically achievable drug concentrations.
Further, when the cancer cells were treated with mixtures containing bisantrene and the widely used, standard-of-care chemotherapy drug doxorubicin, greater cell-killing was seen in 86% of tumour cells relative to doxorubicin alone.
In the current study, bisantrene was tested in the same 143 cancer cell panel in combination with the DNA hypomethylating agent, decitabine.
A larger market and partnering opportunities
Tillett says the new results suggest the clinical use of decitabine could be expanded beyond blood cancers to solid tumours if used with bisantrene.
“It opens up a whole new market for bisantrene and decitabine,” he says.
“What makes it interesting is Astex Pharmaceuticals, owned by Japanese company Otsuka Pharmaceutical, has made an oral version of decitabine and it has only been used for leukaemias.”
Tillett says the results may be potentially of interest to Astex because they’ve had some unsuccessful trials of their formulation of decitabine in solid tumours.
“They ran some trials and found it just doesn’t do anything, so this opens up the opportunity for partnering, which is important for a company like Race,” he says.
Tillett says Astex Pharmaceuticals and Otsuka Pharmaceuticals have always shown great interest in the work of RAC with bisantrene.
“We are currently working with Astex for the upcoming investigator-initiated AML Phase 1/2 trial so they’re supplying their drug and we’re supplying ours,” he says.
“These results just expand the combination of bisantrene and decitabine beyond leukaemia where decitabine is used, such as breast, lung, pancreatic which is where the opportunity becomes much larger.”
Tillett says the generic version of decitabine is IV administered and now off patent.
“Astex came out with a new formulation of decitabine in the form of a pill the patient could take orally and so they were able to get a new patent, and then sell it for the higher price,” he says.
“It is very similar to what we are doing with bisantrene.”
Tillett says doctors don’t often prescribe a single oncology drug on its own but rather in combination.
“This just makes the opportunity for bisantrene even larger, so we’ve done similar work with doxorubicin last year and now with decitabine,” he says.
Tillett says the aim is to get bisantrene approved for use by regulators in combination with other drugs like doxorubicin and decitabine to treat a variety of cancer indications.
“Showing effectiveness with decitabine opens a whole new market because it would be a different patient population to those that are given doxorubicin,” he says.
This article was developed in collaboration with Race Oncology, a * advertiser at the time of publishing.
This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.
https :// *. com .au/health/combining-races-bisantrene-with-decitabine-enhances-cancer-cell-killing-abilities-study-shows/
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