Clinical stage drug development company Pharmaxis Ltd (ASX:PXS, OTC:PMXSF) has released data from a final interim analysis of 10 patients who have completed six months’ treatment with its drug PXS-5505 in an open label phase 2 clinical trial in patients with the bone marrow cancer myelofibrosis.
The data points to an excellent safety profile and promising signs of clinical activity, with 60% of patients who reached the six-month mark showing improved bone marrow fibrosis scores.
“PXS-5505 continues to show not only an excellent safety profile but also promising clinical activity,” MD Anderson Cancer Center Department of Leukemia Assistant Professor Dr Lucia Masarova said.
“The effect on bone marrow fibrosis is particularly exciting for a disease like myelofibrosis, where despite numerous years of research, we do not have any effective anti-fibrotic drugs.
“It is encouraging to see that the majority of 10 patients who completed 24 weeks of therapy also had improvements of symptoms and more importantly, stable or improved blood counts; including in those patients with severe thrombocytopenia.
“These results support plans to continue clinical investigation of the agent, including combinations with JAK inhibitors where the lack of overlapping haematological toxicity would make PXS-5505 an ideal add-on candidate.”
Only company developing pan-LOX inhibitors
“Pharmaxis is the only company with pan-LOX inhibitors in clinical development,” said Pharmaxis CEO Gary Phillips.
“The results from this trial with an oral LOX inhibitor showing significant improvements in fibrosis grade in bone marrow biopsies corroborate the findings of the trial of our topical LOX inhibitor in established skin scars where we saw a 30% reduction in collagen in skin biopsies after only three months treatment.
“Further to the published pre-clinical research showing disease modification in several different indications, this is a mechanism which is now proven to be anti-fibrotic in patients.”
Phillips emphasised that the excellent safety profile of PXS-5505 made it an ideal candidate for combination with JAK inhibitors, which are the current standard of care in myelofibrosis treatment.
“We anticipate that the impact on bone marrow fibrosis and other clinical parameters from the antifibrotic and intracellular effects of LOX inhibition should lead to improved outcomes for patients,” Phillips continued.
“We look forward to FDA feedback on our protocol and expect to start recruitment of this next cohort later this year.”
Interim result details
The phase 2 trial 'MF-101' is designed to demonstrate that PXS-5505, an inhibitor of all lysyl oxidase enzymes (LOX), 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 about one year.
A total of 21 patients were enrolled in the cohort expansion phase of the study with 10 patients having completed 24 weeks of treatment.
PXS-5505 has shown to be well tolerated, with no serious treatment-related adverse events reported, and has promising signs of clinical efficacy including improved symptom scores, stable or improved haematological parameters and reduced bone marrow fibrosis.
10 patients have dropped out of the study due to a lack of clinical response or adverse events unrelated to the drug.
Of the 10 patients completing six months treatment:
- 5/9 evaluable patients had improved bone marrow fibrosis scores of ≥1 grade with 4 out of 5 fibrosis responders demonstrating stable haematological parameters and 3 out of 5 patients reporting symptomatic improvement;
- 4 had an improvement in symptom score of >20%;
- 7 had stable/improved haemoglobin (Hb) counts;
- 8 had stable/improved platelet counts despite 3 out of these 8 patients entering the study with Grade 4 (potentially life-threatening) thrombocytopenia; and
- No spleen volume response (SVR35) was identified.