• PharmAust’s Phase 1 trial of lead drug candidate MPL shows positive signs of slowing MND/ALS progression
  • There are currently no effective treatments to reverse progression of this invariably fatal disease
  • PharmAust expects that MPL could receive orphan drug designation by the TGA and US FDA


PharmAust’s Phase 1 clinical trial of its lead drug candidate monepantel (MPL) in people with Motor Neurone Disease/Amyotrophic Lateral Sclerosis (MND/ALS) is offering hope it could slow progress of the lethal disease.

Clinical-stage biotech PharmAust (ASX:PAA) says results from the interim analysis show that Neurofilament Light Chain (Nfl) protein concentrations in the plasma of participants in its Phase 1 clinical trial didn’t increase following MPL treatment.

The results are a crucial as research suggests a correlation between Nfl increases and MND  progression.

PAA says only one patient in cohorts 1, 2 and 3 showed increased Nfl, while the other
11 showed no significant change in Nfl, which corresponds to stabilised MND progression.

“We are delighted with the results that 11 of 12 trial participants show no significant change in Nfl plasma concentrations and are stable,” PAA executive chairman Dr Roger Aston says.

“MPL has emerged as a  leading  candidate with enormous  potential to aid MND therapy development.

“It’s a fantastic result for PharmAust that MPL is showing a clinical benefit.”

Research has shown that Nfl increases as MND progresses in the early stages of the disease, and then plateaus after about 12 months. The patients in the trial have been monitored for the last 4-10 months and were expected to be in the “ramping up” stage of Nfl concentrations.

The data shows 11 out of 12 patients showed no significant change in Nfl when the expectation was that it should have risen significantly. Surprisingly, in one patient, it actually dropped!!

Interestingly, this Nfl endpoint was the basis of the full approval of RELYVRIO™  received by Amylyx Pharmaceuticals late last year. PharmAust’s results will likely attract some attention from some of the bigger players in the neurodegenerative space.


MPL is a promising treatment for MND

According to the International Alliance  of  ALS/MND  Associations,  MND affects  more than 350,000  people globally, with more than 100,000 people dying from the disease annually.

The MND/ALS  addressable  market is US$3.6 billion annually, with popular current treatment Riluzole reaching ~US$1Bn annual sales.

However, there is no cure and no effective treatment to reverse its progression.

MND is invariably fatal with the average life expectancy of someone with MND being around 27 months.

Independent studies have shown that one-third of patients die within 12 months after the first diagnosis.

Incredibly, patients have been dosed with MPL for up to 10 months in the clinical trial, all are still alive and showed no signs of material adverse events and 11 out of 12 appear “stable”.

The biotech has demonstrated in its preclinical programs that MPL has the potential to activate molecular pathways relevant to the treatment of MND.

MPL could reduce the rate of degeneration and loss of  motor neurons in the brainstem’s anterior horns and motor nuclei.


Orphan Drug Designation

With success in the clinic, PharmAust expects that in due course MPL could receive orphan drug designation by the FDA for the indication of motor neurone disease. Such designations come with a number of financial and supportive benefits.

The Orphan Drug Act provides for granting special status to a drug or biological product to treat a rare disease or condition upon request of a sponsor.


Positive pharmacokinetic analysis

PAA recently completed an interim pharmacokinetic analysis of plasma MPL and Monepantel Sulphone (MPLS) concentrations in cohort 3 MND patients.

Pharmacokinetics is the movement of drugs into, through, and out of the body – essentially the time course of its absorption.

The patients received MPL at 6mg/kg, and the 24-hour intensive pharmacokinetics data demonstrated the presence of MPL and MPLS in all measured patients.

MPL was more rapidly cleared from the plasma of these patients, showing some apparent faster MPLS metabolism.

The average MPLS maximum levels following dosing were ~1.8-fold increased between Cohort 1 and 3, while calculated steady-state MPLS concentrations (Css) were 2.6-fold increased.

PAA says with even higher concentrations in the blood there were still no serious adverse effects which points to a safe drug.


Strong support for trial

This Phase1/2 study is being funded by a commitment of $881,085 made by FightMND, the largest independent funder of MND research in Australia.

Founded in 2014 by former AFL player Neale Daniher, FightMND was established with the purpose of finding effective treatments, and ultimately a cure for MND.

The funding agreement provides that PharmAust shall own all intellectual property generated from the trial.


MPL also benefiting dogs and Louie the Beagle

MPL has also demonstrated objective anticancer activity in dogs, making it uniquely positioned to be commercialised for treatment of human and veterinary cancers.

PAA has been progressing through its Phase 2 B-cell lymphoma trial, which aims to prove that MPL can improve quality of life.

The trial has already seen two dogs experience a +30% reduction in cancer tumour, while another 10 have enjoyed a stable disease response.

PAA also recently highlighted the positive story of 13-year-old Beagle Louie, who has lived comfortably for a year after being treated with MPL without any side effects.



This article was developed in collaboration with PharmAust,  a Stockhead advertiser at the time of publishing.


This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.