PharmAust’s monepantel study shows 58% slowdown in MND progression

A Phase 1 trial into the effects of lead candidate monepantel (MPL) on patients with motor neurone disease MND / amyotrophic lateral sclerosis (ALS) has delivered top-line results for clinical-stage biotech PharmAust (ASX: PAA).

The multi-centre, open-label trial involved a 24-hour escalating single-dose pharmacokinetic (PK) study and a four-week repeated escalating dose study to establish the safety, tolerability and PK parameters of MPL when administered orally to patients.

A total of 12 participants were enrolled in cohorts of six across two sites.

Cohort 1 was administered dose levels of 2 milligrams per kilogram body-weight per day and 6mg/kg/day, while Cohort 2 was administered 4mg/kg/day and 10mg/kg/day.

Participants continued to receive MPL treatment until they were offered dose escalation or until the end of treatment.

Preliminary efficacy data showed a 58% reduction in the rate of disease progression for Cohort 2 using the US Food and Drug Administration’s (FDA) primary efficacy endpoint ALS functional rating scale-revised (ALSFRS-R).

Safety and tolerability

The Phase 1 study showed that MPL displays superior safety and tolerability compared to the leading FDA-approved drug Relyvrio, which is a prescription oral therapy for adults living with ALS and has been shown to help slow disease progression.

The results included no treatment-related deaths, with all patients completing the study and zero dose-limiting toxicities reported.

A total of 56 treatment-emergent adverse events were recorded, with three of them (namely raised liver enzymes, increased hair growth and constipation) considered to be in the “mild” category and possibly related to MPL.

Patients remained on daily treatment for up to 16 months.

On completing the study, all participants continued receiving MPL via a special access scheme and opted to enrol in a 12-month open-label extension.

Cerebrospinal fluid reduction

An analysis of biomarkers among consenting patients also provided evidence that MPL slows disease progression with a large reduction in cerebrospinal fluid neurofilament light chain, a measure of neuronal damage.

Concentrations of MPL sulfone (or MPLS, the active metabolite of MPL) increased proportionally with higher doses of MPL.

MPLS was found in the cerebrospinal fluid indicating that both drugs have the ability to cross the blood-brain barrier.

Exciting milestone

PharmAust chief executive officer Dr Michael Thurn said the positive Phase 1 results were an “exciting milestone” for the company.

“The release of these top-line MEND study results is […] a significant step towards helping people diagnosed with this rare and incurable disease.”

“The 58% slowing in ALSFRS-R decline amongst Cohort 2 participants clearly demonstrates the potential to provide meaningful clinical benefit to people living with MND and ALS,” he said.

“To know that we have potentially prolonged the lives of 12 patients is extremely satisfying and humbling [and] we now look forward to advancing discussions with strategic partners who share our vision for monepantel.”