Clinical stage drug development company Pharmaxis Ltd announced further positive results of data analysis from a phase 1c clinical trial (MF-101) studying its drug PXS-5505 in patients with the bone marrow cancer myelofibrosis for 28 days at three dosage levels.
Assessment with Pharmaxis’ proprietary assays of the highest dose has shown inhibition of the target enzymes, LOX and LOXL2, at greater than 90% over a 24-hour period at day 7 and day 28. The trial safety committee has reviewed the results and having identified no safety signals, has cleared the study to progress to the phase 2 dose expansion phase where 24 patients will be treated at the highest dose twice a day for 6 months.
Pharmaxis CEO Gary Phillips said, “We are very pleased to have completed the dose escalation phase of this study with such clear and positive findings. We will now immediately progress to the phase 2 dose expansion study where we aim to show PXS-5505 is safe to be taken longer term with the disease modifying effects that we have seen in the pre-clinical models. The trial infrastructure and funding is in place and we are on track to complete the study by the end of 2022.”
Independent, peer-reviewed research has demonstrated the upregulation of several lysyl oxidase family members in myelofibrosis. The level of inhibition of LOX achieved in the current study at all three doses significantly exceeds levels that caused disease modifying effects with PXS-5505 in pre-clinical models of myelofibrosis with improvements in blood cell count, diminished spleen size and reduced bone marrow fibrosis. LOXL2 was inhibited to a similar degree and based on pre-clinical work such high inhibition is likely replicated for other LOX family members (LOXL1, 3 and 4). [1] Study data can be viewed in the full announcement.
Commenting on the results of the trial, Dr Gabriela Hobbs, Assistant Professor, Medicine, Harvard Medical School & Clinical Director, Leukaemia, Massachusetts General Hospital said, “Despite improvements in the treatment of myelofibrosis, the only curative therapy remains an allogeneic stem cell transplantation, a therapy that many patients are not eligible for due to its morbidity and mortality. None of the drugs approved to date consistently or meaningfully alter the fibrosis that defines this disease. PXS-5505 has a novel mechanism of action by fully inhibiting all LOX enzymes. An attractive aspect of this drug is that so far in healthy controls and in this phase 1c study in myelofibrosis patients, the drug appears to be very well tolerated. This is meaningful as approved drugs and those that are undergoing study, are associated with abnormal low blood cell counts. Preliminary data thus far, demonstrate that PXS-5505 leads to a dramatic, >90% inhibition of LOX and LOXL2 at one week and 28 days. This confirms what’s been shown in healthy controls as well as mouse models, that this drug can inhibit the LOX enzymes in patients. Inhibiting these enzymes is a novel approach to the treatment of myelofibrosis by preventing the deposition of fibrosis and ultimately reversing the fibrosis that characterizes this disease.”
The phase 1c/2a trial MF-101 cleared by the FDA under the Investigational New Drug (IND) scheme aims to demonstrate that PXS-5505, the lead asset in Pharmaxis’ drug 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. Trial sites will now open to recruit myelofibrosis patients into the 6-month phase 2 study in Australia, South Korea, Taiwan and the USA.
An effective pan-LOX inhibitor for myelofibrosis would open a market that is conservatively estimated at US$1 billion per annum.
While Pharmaxis’ primary focus is the development of PXS-5505 for myelofibrosis, the drug also has potential in several other cancers including liver and pancreatic cancer where it aims to breakdown the fibrotic tissue in the tumour and enhance the effect of chemotherapy treatment.
Trial Design |
|
Name of trial |
PXS5505-MF-101: A phase 1/2a study to evaluate safety, pharmacokinetic and pharmacodynamic dose escalation and expansion study of PXS-5505 in patients with primary, post-polycythaemia vera or post-essential thrombocythemia myelofibrosis |
Trial number |
NCT04676529 |
Primary endpoint |
To determine the safety of PXS-5505 in patients with myelofibrosis |
Secondary endpoints |
|
Blinding status |
Open label |
Placebo controlled |
No |
Trial design |
Randomised, multicentre, 4 week duration phase 1 (dose escalation) followed by 6 month phase 2 (dose expansion) |
Treatment route |
Oral |
Treatment frequency |
Twice daily |
Dose level |
Dose escalation: three escalating doses Dose expansion: one dose |
Number of subjects |
Dose escalation: minimum of three patients to maximum of 18 patients Dose expansion: 24 patients |
Subject selection criteria |
Patients with primary or secondary myelofibrosis who are intolerant, unresponsive or ineligible for treatment with approved JAK inhibitor drugs |
Trial locations |
Dose escalation: Australia (2 sites) and South Korea (4 sites) Dose expansion: Australia, Korea, Taiwan, USA |
Commercial partners involved |
No commercial partner |
Reference: (1) doi.org/10.1002/ajh.23409 |
AUTHORISED FOR RELEASE TO ASX BY:
Pharmaxis Ltd Disclosure Committee. Contact: David McGarvey, Chief Financial Officer and Company Secretary: T +61 2 9454 7203, E david.mcgarvey@pharmaxis.com.au
CONTACT:
Media: Felicity Moffatt: T +61 418 677 701, E felicity.moffatt@pharmaxis.com.au
Investor relations: Rudi Michelson (Monsoon Communications) T +61 411 402 737, E rudim@monsoon.com.au