Pharmaxis Ltd (ASX:PXS) has welcomed the first public presentation of data from a preclinical study of PXS-5505 in the liver cancer, cholangiocarcinoma (CCA) at the Americas Hepato-Pancreato-Biliary Association (AHBPA) conference in Miami, USA.
A research team at the University of Rochester Medical Center in New York State under the guidance of Dr Roberto Hernandez-Alejandro, MD (chief division of transplantation/ hepatobiliary surgery) has been investigating the role of lysyl oxidase enzymes in liver cancer and whether the Pharmaxis cancer drug, PXS-5505 can improve the efficacy of current chemotherapy drugs by inhibiting these enzymes.
CCA is the second most frequently diagnosed primary liver malignancy and has nearly doubled in incidence over the last decade.
“Encouraged by the results”
Pharmaxis chief executive officer Gary Philips said: “The role of LOX enzymes in fibrosis is well established and there is a growing body of evidence that in cancers such as those of the liver and pancreas, the poor outcomes experienced with chemotherapy regimens is due to fibrotic tissue restricting drug access and stimulating growth.
“Pharmaxis is working with a number of independent research groups globally on different tumour types with our anti-fibrotic cancer drug, PXS-5505 and I’m very encouraged by the results presented today by Dr Burchard that show a potential disease modifying role for our drug in liver cancer.
“PXS-5505 is progressing well through a phase 1c/2 clinical trial looking for evidence of disease modifying effects in bone cancer myelofibrosis as a monotherapy.
“Exploring the potential of PXS-5505 to address liver cancers such as cholangiocarcinoma or other cancers where fibrosis is limiting the clinical benefit of our current chemotherapy is something we will continue to assess with our scientific and clinical collaborators.”
Results and discussion
The oral presentation by Dr Paul Burchard, MD at today’s meeting covered two main aspects of the teams’ research:
- Firstly, they examined tumour tissue specimens collected from patients at their institution over a 10-year period and found that patients with CCA have higher levels of LOX enzymes and that this also correlates with poor prognosis;
- Secondly, they examined the effect of PXS-5505 with or without chemotherapy treatment in a pre-clinical model of CCA and found that the combination of PXS-5505 and chemotherapy compared to chemotherapy alone significantly improves survival, delays tumour growth, and reduces intertumoral pressure; and
- As a consequence of their findings they propose that PXS-5505 in combination with standard chemotherapy represents an innovative therapeutic strategy with potential for clinical translation in primary liver malignancy.
Final cohort dosing in phase-1c trial
On August 4, Pharmaxis received results of data analysis from the second of three stages in its phase-1c clinical trial (MF-101) studying a potential new treatment for the bone marrow cancer myelofibrosis.
The increase in dose led to a predictable increase in drug blood levels in patients and showed the same good tolerability seen in the first dose cohort.
The third and final dose cohort of the clinical trial is fully recruited and dosing of all patients is expected to kick off at participating sites in Australian and South Korean hospitals later this week.
Following 28 days on this third dose, the safety and pharmacokinetics of the drug, PXS-5505 will be assessed before selecting the optimal dose to the used in the six-month dose expansion phase 2a to further evaluate safety as well as efficacy.
Sites in other countries including the USA and Taiwan are being engaged in anticipation of the dose expansion phase beginning recruitment to 24 patients this year.