Alterity Therapeutics (ASX:ATH) has announced positive topline data from the ATH434-202 open-label Phase 2 clinical trial in people with multiple system atrophy (MSA).
The ATH434-202 trial evaluated a patient population with more advanced disease than was studied in the company's double-blind Phase 2 trial ATH434-201.
The company said ATH434 has been shown preclinically to reduce α-synuclein pathology and preserve neuronal function by redistributing iron in the central nervous system. The topline data showed that ATH434 conferred a clinical benefit in areas of impairment in MSA and stabilised key biomarkers that underpin the disease's pathology.
It is said that the results from the ATH434-202 trial indicate that ATH434 demonstrated a clinical benefit on the Modified Unified MSA Rating Scale Part I (UMSARS I), as well as stabilisation of overall neurological symptoms. Over the 12-month treatment period, disease progression as assessed with UMSARS I was reduced by approximately half as compared to historical controls. In addition, 30 per cent of participants reported stable neurological symptoms over the course of the study.
"These outcomes are potentially promising as stabilisation of MSA symptoms is unexpected in this patient population," said Alterity. It continued, "On the important symptom of orthostatic hypotension, ATH434 on average stabilised low blood pressure symptoms in study participants. Importantly, the aggregate data indicate that ATH434 has similar clinical efficacy in this advanced MSA population as was observed in the earlier stage patients in Study ATH434-201."
Biomarker endpoints were used to evaluate the potential effect of the drug and target engagement. Alterity said neuroimaging outcomes indicate that ATH434 slowed brain atrophy in MSA-affected areas, as measured by the MSA Atrophy Index (MSA-AI), when compared to placebo-treated participants in Study 201. Moreover, the effects on brain volume were comparable to those observed in participants in the 75 mg dose group in Study 201. In addition, ATH434 led to lower iron accumulation in the putamen and globus pallidus as compared to placebo-treated patients in Study 201, providing further evidence of target engagement.
“I am very encouraged by the positive results from the ATH434-202 trial, as they reinforce the robust efficacy we observed in our double-blind study,” said Dr David Stamler, CEO of Alterity. “The data from our Phase 2 studies are consistent and strongly support advancing our ATH434 program in MSA. 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.”