Hey rakeshnirzari1, and anyone else who reads this,
I've been wanting to find some time to sit down and go over these presentations and give you my response to the presentations which to me are extremely impressive and positive. Please note the following is my opinion only (MOO), please do your own research.
Dr Stamler's opening line, '
The aggregate data from our double-blind trial continue to demonstrate the potential of ATH434
as a disease modifying therapy for MSA'said David Stamler, M.D., Chief Executive Officer of Alterity - Accurate in every level when reading the information provided from the presentations that follow in the release.
ATH434 Slowed Disease Progression in a Phase 2 Study in Multiple System Atrophy:UMSARS I is the key outcome measure of interest to regulatory authoritiessuch as the FDA - Regulatory authorities (plural), more than just the FDA, therefore the EU is definitely not excluded.
baseline data revealed that severe OH was substantially higher in the 75 mg group (29.2% vs 4% in 50 mg and 4.5% in placebo) at enrollment, a new analysis of the USMARS I was conducted that included the baseline OH systolic blood pressure change as a covariate - covariate meaning -
an independent variable that can influence the outcome of a given statistical trial, but which is not of direct interest.When this variable was included in the analysis of the UMSARS I at 52 weeks, the efficacy signal in 75 mg dose group strengthened to -2.8 points for a relative treatment effect of 35%. This baseline difference in severe OH largely explains the different responses in 50mg and 75 mg treatment groups. Notably, ATH434 demonstrated a beneficial effect on OH symptoms as assessed with the OH Symptom Assessment, a patient reported outcome -It was extremely pleasing to see an increase in the improvement of the OH number from this ongoing data analysis, giving strength to ATH434 and further support for the administration of 75mg over 50mg (OH = Orthostatic hypotension).
Increased activity in the outpatient setting, as measured by wearable movement sensors, was observed at both dose levels as compared to placebo, with clinically meaningful improvements in step count, total walking time, bouts of walking, and total standing time - Further confirmation of independent patient-based improvement over the placebo group, significantly strengthens the need for ATH434 in this neurodegenerative parkinsonian group, which had been stated by the team, will be a highlight for the FDA to see actual patient improvement other than just biomarker improvements.
Regarding neuroimaging data in 61 participants, ATH434 demonstrated target engagement by reducing iron accumulation at both dose levels compared to placebo in the globus pallidus, and in the putamen and substantia nigra at the 50 mg dose level. In addition, ATH434 demonstrated trends in reducing brain atrophy at both dose levels compared to placebo. ATH434 was well tolerated with similar adverse event rates compared to placebo and no serious or severe adverse events attributed to ATH434 - Viewing the images in (Figure 1) from
The MSA Atrophy Index (MSA‐AI): An Imaging Marker for Diagnosis and Clinical Progression in Multiple System Atrophy - Trujillo - 2025 - Annals of Clinical and Translational Neurology - Wiley Online Library paper from the biomuse study and comparing MSA-P to MSA-C, it was mind blowing to see the amount of atrophy that occurs at these areas of the brain. Although I am not going to highlight every single aspect of the paper, the conclusion provided a strong desire and requirement for a much larger study group to confirm imaging findings, which to me appears extremely sound in the current findings and use throughout phase 3.
Relationship Between Alpha-Synuclein Aggregation Profiles, Imaging Biomarkers, and Disease Severity in a Phase 2 Study of ATH434 in MSADr. Bradbury’s presentation the imaging biomarkers utilized in the ATH434-201 trial presented supportive features of MSA in 96.1% of the 77 enrolled subjects as compared to 78.9% for α-synuclein aggregation profiles in cerebrospinal fluid (CSF) alone (60 of 76) - Which correlates to the conclusion statement above.
Of the 11 participants with an α-synuclein aggregation profile consistent with Parkinson’s disease and/or dementia with Lewy bodies, 80%
demonstrated supportive imaging features of MSA. Two of the 5 participants without evidence of α-synuclein aggregation had imaging consistent with MSA. Therefore, the presentation concludes that a multimodal approach combining α-synuclein aggregation profiles with clinical and imaging data may enhance diagnostic accuracy in MSA - I feel this segment bodes very strongly for the use of ATH434 in the given neurodegenerative diseases (PD & DLB), as both show relatively high levels of a-syn biomarkers, in which ATH434 has successfully shown to reduce (value numbers and % has not yet been released), therefore should assist Alterity reach, or eventually reach AA approval for these diseases, than other iron related diseases (ferroptosis) which
@pivalde has been mentioning. Reading papers on ferroptosis, there is definitely a very strong growing correlation with excess iron related disorders where hopefully and eventually ATH434 can fit in perfectly, particularly, as mentioned several times before no other iron chelating drugs have been able to achieve successful iron from cells without worsening the disease, especially when there are only 3-4 iron chelating mediations available which 2 are the mainly used for haemochromatosis.
Differences Between Clinical and Imaging Phenotypes in Phase 2 Study of ATH434 in Multiple System AtrophyDr. Trujillo’s presentation assessed the two main clinical phenotypes of MSA in Alterity’s ATH434
201 trial: the parkinsonian (MSA-P, n=47) and cerebellar (MSA-C, n=25) - Again the images from the paper highlighted above in figure 1 is quite amazing to see the differences between MSA-P and MSA-C.
results show that quantitative MRI largely complements clinical classification (90% concordance), reinforcing its role as an objective biomarker. The observed discordance (10%) suggests MRI may capture underlying pathology not evident clinically, highlighting its value in refining diagnosis and tracking disease evolution - The high level of clarification than also the 10% capture of underlying pathology that has not been able to be clinically identified, finds this tool incredibly useful in providing the pieces of accurately diagnosing MSA, which will than accurately increase the number of MSA patients, which would also than lead to ATH434 administration.
Overall, reading this presentation release than the associated imaging paper, has shown just how incredibly fruitful and accurate Dr Stamler has been to really drive home the reasons for the way they have conducted the trials, and what an absolute pleasure it is, and should be for everyone to be a part of it. I'm not sure who made this statement, but to a point I definitely agree, that if ATH434 can reach the highs of treating/controlling an uncontrollable disease, then other ferroptosis related illnesses which
@pivalde has mentioned, I do believe this could be in line with a meritorious recognition to Dr Stamler.
Although we all wait with bated breath and at times great annoyance, we need to be assured from these latest presentations, we are on a steadfast track to a meeting with the FDA and commencement of phase 3. What happens there after is just a waiting game and release of information to see where Alterity head.
Again, patience is key, I expect big news by the end of the year which is 10wks away. Remember 2 more presentations to come within the next 5wks.
Anyways, best be off, remember the above is MOO, please DYOR.
