Alterity reports positive results from open-label phase II trial of neurological disease drug

Alterity Therapeutics reports positive topline results from open-label phase II clinical trial of lead drug ATH434 in multiple system atrophy.

ATH434 continues to show promise for treating MSA. Pic: Getty Images

Special Report: Alterity Therapeutics has reported positive topline results from its open-label phase II clinical trial of lead drug ATH434, offering encouraging signs for the treatment of multiple system atrophy (MSA). 

• Alterity reports positive topline data from open-label phase II trial of ATH434 in multiple system atrophy
• ATH434 demonstrated clinical benefit on Unified MSA Rating Scale and global measures of neurological symptoms
• Neuroimaging biomarkers showed target engagement and slowed brain atrophy with drug well tolerated and having a favourable safety profile

The study, conducted in a patient population with more advanced disease than in the Alterity Therapeutics’ (ASX:ATH) double-blind phase II trial, showed ATH434 was well tolerated and provided measurable clinical benefits, including stabilisation of neurological symptoms and slowed brain atrophy.

Over the 12-month treatment period, results indicated patients treated with ATH434 showed ~50% less disease progression on the Modified Unified MSA Rating Scale (UMSARS I) compared to historical controls.

Notably, 30% of participants reported stable or improved symptoms – an uncommon result in this advanced patient group. 

In further encouraging results, 30% of participants also stabilised or improved on the Patient Global Impression of Change (PGIC) scale, which asks the patient to evaluate their overall neurological symptoms as compared to immediately before starting therapy.

ATH434 also helped stabilise symptoms of orthostatic hypotension, a common and serious drop in blood pressure when standing, in study participants. 

Notably, the overall results suggest that ATH434 was just as effective in this more advanced group of MSA patients as it was in earlier-stage patients from the previous phase II double-blinded trial. 

Neuroimaging data provided further support, showing a slowing of brain volume loss in MSA-affected regions and reduced iron accumulation – both consistent with the proposed mechanism of ATH434, which targets excess brain iron thought to drive MSA pathology.

Novel approach could provide much-needed therapy

Alterity’s lead indication, MSA, is a rare and aggressive parkinsonian disorder with up to 50,000 patients in the US, driven by excess iron and aggregation of a protein called alpha-synuclein in the central nervous system.

ATH434 takes a novel approach to MSA by addressing iron imbalance and protein aggregation, offering what could be the first disease-modifying therapy. 

The drug has been granted both fast track and orphan drug designations by the US Food and Drug Administration, as well as orphan drug status in the EU.

Backed by promising phase II and open-label phase II results, Alterity is chasing a market opportunity exceeding US$1.1 billion with ATH434. 

About the open-label study

The phase II open label trial (ATH-434-202) was an open-label study in advanced MSA.

The trial enrolled participants diagnosed with MSA using a multimodal approach (clinical, neuroimaging, fluid biomarkers), who were treated with oral ATH434 75mg twice daily for 12 months. 

The study assessed the safety and efficacy of ATH434 treatment on clinical and biomarker endpoints. 

The pre-specified key clinical endpoints included the modified UMSARS I, the clinical global impression of change, and the patient global impression of change.

Enrolled participants were more advanced than those in the double-blind ATH434-201 phase II trial based on baseline variables including duration of motor symptoms, UMSARS I score, frequency of severe orthostatic hypotension, and plasma NFL levels.

Based on the observed clinical and neuroimaging data, ATH434 improved overall neurological symptoms and slowed disease progression compared to historical data.

‘Strongly support advancing our ATH434 program’

CEO Dr David Stamler said he was very encouraged by the positive results from the ATH434-202 trial, as they reinforce the robust efficacy we observed in its phase II study. 

“The data from our phase II studies are consistent and strongly support advancing our ATH434 program in MSA,” he said. 

“With the favourable clinical and biomarker outcomes we have seen, we continue to believe that ATH434 has the potential to slow the progression of this devastating disease. 

“We are committed to bringing this new therapy to patients as soon as possible.”

The trial’s lead investigator, professor Daniel Claassen from Vanderbilt University Medical Centre said the results were very helpful in establishing the clinical response to therapy. 

He said the consistent changes in UMSARS, along with quantitative measures in imaging, support the findings noted in the phase II trial. 

“Currently, there are no disease modifying medications for the treatment of MSA, and these data encourage the continued development of ATH434 to treat this disease,” he said. 

“We are indebted to the study participants and their families who contributed to this study.”

This article was developed in collaboration with Alterity Therapeutics, 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.