Australian clinical-stage drug development company Pharmaxis (ASX:PXS) has concluded an interim analysis of data from six patients who have completed six months of treatment with PXS-5505 in its open-label phase 2 clinical trial in patients with the bone marrow cancer myelofibrosis.
The phase 2 trial known as MF-101 was cleared by the US FDA under the Investigational New Drug (IND) scheme.
Pharmaxis said the study aims to demonstrate that PXS-5505, which it describes as the lead asset in its discovery pipeline, is safe and effective as a monotherapy in myelofibrosis patients who are intolerant, unresponsive or ineligible for treatment with approved JAK inhibitor drugs.
These patients have very limited treatment options and a life expectancy of approximately one year.
A total of 15 patients have been enrolled in the cohort expansion phase of the study with six patients having completed 24 weeks of treatment. Four patients have dropped out of the study due to a lack of clinical response.
The company said that PXS-5505 has been well tolerated with no serious treatment-related adverse events, two of the six patients have a clinically important improvement in symptoms, five of the six have either stable or improved bone marrow fibrosis scores, and the same number have stable or improved platelet and/or haemoglobin scores. No reductions were seen in spleen volume.
Dr Gabriela Hobbs, assistant professor of medicine at Harvard Medical School and clinical director of the Leukemia Service at Massachusetts General Hospital, said, “PXS-5505 continues to be very well tolerated in the clinic with no serious treatment-related adverse events reported. Though still early in the dose expansion phase of the study, PXS-5505 appears to be stabilising and in some cases, improving the hemoglobin and platelet counts, which has also been associated with symptom improvements in those patients that were treated to 24 weeks.
“This is encouraging given the poor prognoses seen after ruxolitinib discontinuation with a median overall survival of only 11-14 months, typical of this study population. These results support further clinical investigation of PXS-5505 in myelofibrosis.”
Pharmaxis said that a total of 18 clinical trial sites are now actively recruiting in Australia, South Korea, Taiwan and the US with two more sites due to open this year. Recruitment is expected to complete by the end of 2022 with top-line results available in 2023.
CEO Gary Phillips said, “We are confident that these results, if repeated in the whole study population, will satisfy regulatory requirements to continue the development of PXS-5505 in myelofibrosis and also excite clinicians, patients and industry groups who are closely following our progress with this novel mechanism. The excellent target enzyme inhibition and safety profile seen in previous studies has been maintained when the treatment periods have been extended to 6 months and the signs of efficacy to date are compatible with the disease-modifying effect witnessed in the pre-clinical studies.
“This study is recruiting patients who have already failed on a JAK inhibitor or been deemed to be ineligible. We have ended up with a very heterogeneous group of patients who have often run out of treatment options. This is an excellent context for demonstrating the safety profile of PXS-5505 in a wide range of circumstances, but is challenging when looking for consistent results in efficacy when the baseline assessments are so varied. We anticipate that with longer treatment periods or combination with a JAK inhibitor in patients with less severe disease we will see further improvements in bone marrow fibrosis and blood cell counts as well as the subsequent reductions in spleen volume that would result from this disease-modifying mechanism.”
The company said the development of PXS-5505 for myelofibrosis is its primary focus but that it also has potential in several other cancers including liver and pancreatic cancer where it aims to break down the fibrotic tissue in tumours and enhance the chemotherapy treatment.
An investigator-led phase 1c study in newly diagnosed hepatocellular cancer patients, where PXS-5505 will be used in addition to immunotherapy standard of care, is due to commence recruitment at Rochester University New York in late 2022.