Clinical-stage biotechnology company PharmAust Limited (ASX: PAA) has reported the first patient of the second cohort has been dosed in its Phase 1/2 Trial testing the effects of monepantel (MPL) in individuals living with motor neurone disease (MND).
MPL was well tolerated by all MND patients at the first dosing level and pharmacokinetics (PK) confirmed drug absorption. PharmAust will continue to supply MPL tablets to all six patients in Cohort 1 that elected to remain on the treatment. The first patient to be dosed has now surpassed 140 days of MPL treatment with no material safety issues or Serious Adverse Events (SAEs).
Patients from Cohort 1 will continue to be monitored for cognitive function with ALSFRS-R (ALS Functional Rating Scale – Revised) being collected monthly. At the end of each dosing visit, all 3 scales are collected; ALSFRS-R, ALSQOL (Quality of Life Assessment Questionnaire) and ECAS (Edinburgh Cognitive and Behavioural ALS Screen).
Progression of the trial with concomitant escalation of MPL dosing is consistent with the good safety profile during the Cohort 1 stage of the study and that all of the Cohort 1 patients have elected to remain on the drug. Furthermore, the Safety Monitoring Committee has reviewed the safety data and pharmacokinetics from the first dosage level and authorised progression of the trial to the Cohort 2 stage.
PharmAust will now focus on enrolling a further five patients to complete the Cohort 2 group of six patients in its Phase 1/2 clinical trial. The outcome of this rising dose study will be a key determinant in proceeding to a Phase 2 trial in MND.
Continued safety and efficacy data from the trial will also be used to facilitate a Phase 2 study in COVID- 19 patients.
PharmAust previously announced it received a funding commitment of A$881,085 for a Phase 1/2 trial examining the effects of MPL in MND, otherwise known as Lou Gehrig’s disease or Amyotrophic Lateral Sclerosis (ALS). These funds were granted by FightMND, the largest independent funder of MND research in Australia.
The trial is overseen by Dr Susan Mathers of Calvary Health Care, Bethlehem, Statewide Progressive Neurological Disease Service, Melbourne and will include a second trial site headed by Professor Dominic Rowe of the Centre for Motor Neurone Disease Research Faculty of Medicine and Health Research at Macquarie University, Sydney. The funding agreement provides that PharmAust shall own all intellectual property generated from the trial.
The phase 1/2 clinical study is determining the tolerability, safety, pharmacokinetics and preliminary efficacy of oral MPL in MND sufferers. The trial is open label and comprises a four week escalating dose of MPL.
According to the International Alliance of ALS/MND Associations, MND affects over 350,000 people globally and kills more than 100,000 people every year. The disease is invariably fatal, with the average life expectancy of someone who has MND being just around 27 months. The MND/ALS addressable market is US$3.6Bn per annum with Riluzole already reaching ~US$1 billion in annual sales.
PharmAust demonstrated in its preclinical programs that MPL has the potential to activate molecular pathways relevant to the treatment of MND. MPL could potentially reduce the rate of degeneration and loss of motor neurons in the anterior horns and motor nuclei of the brainstem. There are also a number of surrogate clinical endpoints to be determined during the trial. PharmAust has developed and manufactured a bespoke monepantel tablet for the trial.
With success in the clinic PharmAust hopes that in due course MPL could receive orphan drug designation by the TGA and FDA for the indication of motor neurone disease. Such designations come with a number of financial and supportive benefits and this opportunity is currently being evaluated by PAA.
