BioMed up-and-comer FivepHusion is looking to set the new standard of care for chemotherapy treatments with its flagship Deflexifol™ primed to solve a decades-long issue plaguing oncologists in their treatment of cancer patients.
A significant limitation with current chemotherapy is sub-optimal co-exposure of the drugs 5-FU and LV, which are both necessary for optimal anti-cancer activity, but are chemically incompatible.
5-FU and LV are referred to as the “backbone” of modern chemotherapy for metastatic colorectal cancer and many other solid tumours as they are standardly administered by themselves or in combination with other drugs.
However, the high alkalinity of current 5-FU formulations causes LV to precipitate, resulting in serious safety risks through potential blockage of the surgically implanted catheters utilised to administer these and other drugs to patients in chemotherapy.
Consequently, 5-FU and LV are currently sequentially administered to patients to prevent precipitation risk, leading to very limited 5-FU / LV co-exposure (less than 10%) during a typical treatment cycle.
Additionally, the high pH of 5-FU formulations results in a number of harmful side effects for patients, including phlebitis (venous inflammation), further limiting the safety and tolerability of this mainstay treatment.
“Deflexifol™ solves a forty-year-old problem with the formulation and administration of 5-FU and LV. We are not aware of any other drugs in development that solve this problem so elegantly and effectively,” FivepHusion Chief Executive Dr Christian Toouli said.
The proprietary Deflexifol™ formulation uses a cyclodextrin (sugar) excipient to co-formulate 5-FU and LV at a physiological (safer) pH so the LV won’t precipitate, allowing the two drugs to be safely administered to patients together to optimally co-expose the tumour and effectively kill cancer cells.
To date, Deflexifol™ has been used to treat 58 end-stage cancer patients and was efficacious in most patients, including those whose previous 5-FU/LV treatments had failed, indicating the potential superior efficacy of Deflexifol™ over standard formulations.
“Both trials have recruited end-stage cancer patients, who have typically been heavily pre-treated with a variety of drugs, including 5-FU and LV. Remarkably, the treating oncologists have observed responses in patients whose tumours have previously stopped responding to 5-FU therapy,” states Toouli.
“Responses after re-challenge with chemotherapy are very uncommon, supporting the view that Deflexifol™ optimises the delivery of these drugs, thus providing a superior benefit to patients above what they had experienced with the standard of care.”
Greater safety & tolerability
On top of this superior efficacy, patients have also reported that Deflexifol™ is substantially more tolerable than 5-FU, with a maximum tolerated dose of Deflexifol™ predicted to be substantially higher than the standard-of-care doses of 5-FU administered in clinical practice.
“To date, clinical trials have reported a lower frequency and severity of well-understood standard toxicities associated with 5-FU, when equivalent doses are delivered by Deflexifol,” Toouli said.
“The enhanced safety profile of Deflexifol™ has also led to greater tolerability of higher equivalent doses of 5-FU administered to patients. We are currently completing a second clinical trial that will confirm the maximum tolerated dose in patients when treated with Deflexifol in a regimen that mimics the standard of care 5-FU and LV treatment regimen .”
“This is important, as the data to date suggests that we can tolerably deliver a lot more of the active anti-cancer agent via Deflexifol™, increasing the potential of our drug to destroy the tumour.”
A New Backbone for Chemotherapy
With these results, Deflexifol™ is well-positioned to replace 5-FU+LV therapy as the new Gold Standard of Care™, providing superior efficacy and enhanced clinical benefits.
“We are developing Deflexifol™ to be the new standard of care for treating solid tumours that are currently treated with 5-FU and LV. These tumours have an incidence of up to 6 million patients per year. Deflexifol™ has the potential to provide greater safety and tolerability, and superior efficacy for these cancer patients, whilst also being “bioequivalent” to proven drugs (5-FU and LV) that oncologists are very familiar with and which they standardly use every day.”
Most interesting is that FivepHusion expects Deflexifol™ to completely replace former 5-FU/LV formulations as the new treatment “backbone” onto which other existing and new therapeutics will be combined. As a result, Toouli commented “We expect other new drugs in development to be combined with Deflexifol™ instead of 5-FU/LV. Thus, the development pipeline is not a competitor to Deflexifol™, but rather complements our vision to treat patients safely and effectively.”
FivepHusion is now well on its way towards late-stage clinical development and registration for Deflexifol™ following a successful engagement with the FDA last December. The Agency confirmed that Deflexifol™ may be immediately developed for the first-line treatment of metastatic bowel cancer patients and only one successful phase III pivotal trial is required to support its registration.
“We are raising capital now to accelerate towards initiation of a phase III registration trial in metastatic colorectal cancer, the trial that will facilitate the registration and global commercial launch of Deflexifol™. Incoming capital will be utilised for preparatory activities required for the phase III trial and also to explore the use of Deflexifol™ to treat paediatric brain cancer.”
“Metastatic colorectal cancer and paediatric brain cancer have significant unmet medical needs and thus represent very attractive market opportunities. We are planning multiple value catalysts over the next 12 months with a potential IPO planned for 2024” Toouli stated.
Deflexifol™ and Gold Standard of Care™ are trademarks of FivepHusion.