Clinical-stage biotechnology company PharmAust (ASX: PAA) has dosed the first patient in an Open-Label Extension (OLE) study at Calvary Health Care Bethlehem, Melbourne.
The OLE study will investigate the long-term safety, tolerability, and efficacy of monepantel (MPL) in patients with Motor Neurone Disease (MND)/Amyotrophic Lateral Sclerosis (ALS) who previously completed the Phase 1 MEND Study.
In December 2023, the company announced the completion of the Phase 1 MEND study, involving two cohorts of six patients, each progressively receiving higher dose levels of MPL in a staggered design approach over time.
All 12 patients have elected to continue treatment with MPL through a compassionate-use program and are now willing and able to participate in the 12-month OLE study. Patients will receive a daily dose of 10 mg/kg body weight of MPL for an additional 12 months during the OLE study, to further test if MPL will safely reduce disease- associated protein accumulation in motor neurons and provide therapeutic benefits for patients with MND/ALS.
The OLE study involves two sites in Australia, Calvary Health Care Bethlehem, led by Associate Professor Susan Mathers and Macquarie University, led by Professor Dominic Rowe.
Survival estimations/statistical review
To assess the likelihood of a 100% survival rate among the 12 Phase 1 MEND patients without treatment, statistical consultant specialists and PharmAust partner Berry Consultants utilises baseline survival rates derived from historical control data within the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.
After adjusting for differing diagnosis durations, Berry’s analysis involved comparing patients in the PRO-ACT database with similar characteristics to those in PharmAust’s Phase 1 study. Berry’s conservative sensitivity analyses identified the one-year study survival rate estimate of 67.7% with a 95% Confidence Interval. Considering differential diagnosis durations, the probability estimates of all 12 Phase 1 MEND patients surviving today without treatment are less than 0.1% (less than 1 in 1,000).
The PRO-ACT database is the largest publicly available repository of merged ALS clinical study data. Clinical study data were pooled from 16 completed Phase 2/3 ALS/MND clinical studies and one observational study.
Over 8 million de-identified longitudinally collected data points from more than 8,600 persons with ALS were standardised across studies and merged to create the PRO-ACT database. This database includes demographics, family histories, and longitudinal clinical and laboratory data.
