PAA has released positive interim results from its ongoing OLE study. Pic: Getty Images
Health & Biotech
Special Report: PharmAust has released promising interim results from its ongoing open-label extension study of its lead drug monepantel to treat Amyotrophic Lateral Sclerosis.
PharmAust (ASX:PAA) says the study showed that monepantel, or MPL, administered at a daily dose of 10mg/kg, continues to be well tolerated and slows disease progression while improving survival rates.
Compared to untreated ALS patients from a historical database, those on MPL experienced significantly longer survival, an 80.3% reduced risk of death, and a 43.2% slower rate of functional decline.
Crucially, PAA said 56% of the patients showed no functional decline at all.
PAA said some patients have been on MPL for up to 23 months, and the ongoing positive results are encouraging for the upcoming Phase 2/3 study within the HEALEY ALS Platform Trial, which is expected to start enrolling participant’s next quarter.
The company announced in July MPL was selected for inclusion in the prestigious HEALEY ALS Platform Trial in the US under a Clinical Research Support Agreement with Massachusetts General Hospital, the largest teaching hospital of Harvard Medical School.
The OLE study investigates the long-term safety, tolerability, and efficacy of MPL in patients with ALS with 10 of the 12 patients who previously completed the Phase 1 MEND study last year successfully enrolled.
Of the two patients who didn’t enrol in the OLE study, one died due to disease progression while on the compassionate use program, and the other did not meet the study’s inclusion criteria due to elevated liver enzymes and has since died from ALS progression.
PAA said a third patient died after starting the OLE study, from complications associated with pneumonia unrelated to treatment with MPL. Nine of the original 12 patients who started the Phase 1 MEND Study remain in the OLE study and continue to receive MPL treatment.
Eligible patients in the OLE program receive a daily dose of 10 mg/kg body weight of MPL for 12 months.
The OLE study is being conducted at two clinical sites in Australia including Calvary Health Care Bethlehem, led by Associate Professor Susan Mathers, and Macquarie University, led by Professor Dominic Rowe.
PAA’s statistical partners Berry Consultants have provided an updated survival probability analysis to quantify the survival benefit of MPL treatment compared to untreated matched controls from the PRO-ACT historical control database.
As of August 24, 2024, patients have been treated with MPL for varying durations, ranging from 11.3 to 22.7 months (median of 18.5 months) and at varying dose levels (2 to 10 mg/kg/day).
Using disease onset location, pre-baseline ALSFRS-R slope, baseline ALSFRS-R score, and time since disease onset, Berry Consultants matched untreated PRO-ACT controls to each MPL-treated patient.
The PRO-ACT database is the largest publicly available repository of merged ALS clinical study data.
The Kaplan-Meier curves shown below illustrate the differences in estimated survival probability across four different analysis datasets, from least (overestimating survival) to most conservative (underestimating survival).
PAA said regardless of the dataset used, MPL treatment significantly extended survival compared to untreated matched controls from the PRO-ACT database.
PAA said disease progression in the OLE study is being tracked by assessing each patient’s ALS Functional Rating Score-Revised (ALSFRS-R) score bimonthly.
The ALSFRS-R is a tool used to measure the functional status of individuals with MND/ALS, assessing various aspects of daily functioning, including mobility, self-care, speech, and swallowing.
The chart shows the mean rate of decline and each individual patient’s ALSFRS-R score at baseline, months two and four visits.
The mean rate of decline over the four months for the nine patients treated daily with MPL was 0.41 ALSFRS-R points per month compared to an estimated 0.71 ALSFRS-R points per month by Berry Consultants.
PAA said this corresponds to a 42% slowing in ALSFRS-R decline in just over four months.
Additionally, five out of nine patients (56%) treated with MPL showed no decline in motor function over the four months from baseline.
Meanwhile PAA said its application submitted in March for FightMND grant funding to help cover the costs of its planned Phase 2 study was unsuccessful.
However, the company said FightMND has played a vital role in the early clinical development of MPL, fully funding the successful Phase 1 MEND study.
PAA since the grant application was made, MPL secured selection for inclusion in the HEALEY ALS Platform Trial, which does not allow for study sites in Australia and its application was therefore no longer eligible for funding.
However, the company said inclusion in the HEALEY ALS Platform Trial offers substantial financial and operational advantages for PAA, providing the company with the most cost-efficient and safest accelerated pathway to bring MPL to all patients.
PAA managing director Dr Michael Thurn said the latest results are “extremely encouraging” and continue to emphasise the excellent long-term safety profile and potential of MPL to increase the life expectancy of the very vulnerable patient population.
“In October, we will reach the two-year anniversary since the first patients started treatment with MPL,” he said.
“We have made incredible progress over this period, including engaging with the US FDA regarding the development pathway for MPL via a Pre-Investigational New Drug meeting, being granted Orphan Drug Designation from the US FDA, and more recently, having monepantel selected for inclusion in the prestigious HEALEY ALS Platform Trial.
“We’re very excited about the path ahead and the potential to help more patients.”
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.
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