Actinogen Medical Ltd (ASX:ACW, OTC:ATGGF) earlier this week completed the final patient visit in its pivotal XanaMIA Phase 2b/3 Alzheimer's disease trial, putting the company on course to report top-line results in November.
CFO Will Souter told Proactive that reaching the final patient visit represented "a major milestone in any clinical trial", following an interim analysis earlier in the year and three meetings of the independent data monitoring committee.
Souter said the milestone also provided greater certainty around the timing of the final results after patients had been on treatment for 36 months.
A key feature of XanaMIA is the use of the p-tau181 blood biomarker to select patients. Souter explained that analysis of participants in a prior Actinogen Medical study had identified a positive trend towards Xanamem being an effective treatment among patients with elevated levels of the biomarker, who were considered more likely to have Alzheimer's disease.
For XanaMIA, participants were tested for elevated p-tau181 before entering the study. Souter said this meant the study cohort was more likely to have Alzheimer's disease and more likely to progress during the treatment period.
The November readout therefore represents a major potential catalyst for Actinogen Medical. The company is looking for evidence that patients treated with Xanamem deteriorate more slowly than those receiving placebo, with Souter saying patients could potentially stabilise.
He said the company was targeting an effect close to twice that demonstrated by existing antibody drugs, adding that achieving this would represent "a major achievement and a significant outcome" for patients and Actinogen Medical.
A positive readout could also set up the company's next clinical and regulatory steps. Souter said Actinogen Medical was already actively planning a final Phase 3 study, which would be larger and extend across more jurisdictions, geographies and demographics.
The current trial covers 35 sites across Australia and the US.
Souter said Actinogen Medical had confirmed with both the US Food and Drug Administration and the European Medicines Agency that one further pivotal trial would be needed to reach marketing approval.
He added that sufficiently strong XanaMIA results could prompt discussions with the FDA about accelerated approval. Souter characterised that prospect as "a long shot", but said it was not out of the question and that the company would return to regulators immediately if the results were particularly positive.
Interview highlights
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Actinogen Medical has completed the final patient visit in its pivotal XanaMIA Phase 2b/3 Alzheimer's disease trial, with top-line results expected in November.
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Souter described the milestone as significant following an interim analysis and three independent data monitoring committee meetings.
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The trial uses the p-tau181 blood biomarker to help identify participants more likely to have Alzheimer's disease and to experience disease progression.
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Actinogen Medical is assessing whether patients receiving Xanamem deteriorate more slowly than patients receiving placebo, with stabilisation also a potential outcome.
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Souter said the company is targeting an effect close to twice that of existing antibody treatments.
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Actinogen Medical is already planning a final Phase 3 trial if the XanaMIA results are positive.
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The proposed Phase 3 study would be larger and cover more jurisdictions, geographies and demographics than the current study, which spans 35 sites in Australia and the US.
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Souter said the company has confirmed with the FDA and EMA that one further pivotal trial would be required to reach marketing approval.
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Actinogen Medical also intends to discuss potential accelerated approval with the FDA if the results are sufficiently strong, although Souter described this possibility as "a long shot".
Proactive: Actinogen Medical has completed the final patient visit in its pivotal XanaMIA Phase 2b/3 Alzheimer's disease trial, keeping top-line results from the closely watched study on track for release in November. Here to discuss the trial and what to expect next is CFO Will Souter. Will, good to see you again. It's always a pleasure. Talk us through what completing this final patient visit means for the trial.
Will Souter: It's a major milestone in any clinical trial to reach that final patient visit. It means that things have gone well. We've been able to progress, in our case, through an interim analysis earlier, back in January this year. We've had three meetings of our independent data monitoring committee, confirming safety along the way, as well as the interim assessment of efficacy.
It's a very significant milestone. It's also a significant milestone for the team that has been involved in this. Having patients on treatment for 36 months is a relatively long trial, especially for a small company like Actinogen. So, it's a huge amount of time, effort and energy that's gone into getting to this point.
But it also means we now know, with a much higher degree of certainty, when our final results will be coming out, which is November.
Proactive: We'll get to November in a second. Can you talk me through why the p-tau181 biomarker used to select patients for the trial is important?
Will Souter: We had the benefit of being able to look at the prior Alzheimer's disease trial that Actinogen did in a larger cohort of people, where we weren't able to take a blood sample and do a blood test at the time of enrolling those patients.
We were able to go back and identify, from that cohort of patients, using this new blood biomarker, which patients had elevated levels of this protein in the blood, p-tau181.
When we looked at that group of patients from that prior trial — the ones that were therefore more likely to have actually had Alzheimer's disease — we showed a really positive trend towards Xanamem being an effective treatment.
What we've done is test all of the people coming into this current trial to confirm that they do have that elevated level of p-tau181.
That's become quite a common biomarker to use now to diagnose, with a high degree of sensitivity and specificity, Alzheimer's disease. That means the cohort we've got in this current trial is more likely, if not certain, to have Alzheimer's disease and also more likely to progress more quickly.
Over that 36-month treatment period, we want to see some patients who are on placebo deteriorating as normal, and other patients who are on our drug not deteriorating, or perhaps even stabilising. That's what we're looking for in this trial. By enrolling using that biomarker, that enhances the chances of that being successful.
Proactive: You've pretty much answered my next question there — what you're looking at in those top-line results expected in November.
Will Souter: Obviously, there are some other treatments for Alzheimer's disease available on the market. These antibody treatments show a very, very modest effect. They have been statistically significant but perhaps not clinically significant.
When we talk to doctors in the field, others who are involved, caregivers and so on, it's clear that there's a need for another type of treatment.
Our trial is designed to be better than those antibody drugs that are on the market. It's a relatively low bar for success. If we do a bit better than them, we don't have to stabilise patients. We don't have to cure Alzheimer's disease. We just have to do a bit better than those existing treatments on the market to have a very positive result.
That's what we're targeting. We're targeting close to two times better than those antibody drugs. That would be a major achievement and a significant outcome for patients and, obviously, for the company.
Proactive: Finally, should results be positive, what are the next steps?
Will Souter: We're very actively planning a final Phase 3 trial, which would follow positive results. That would be a bigger trial. It would be across more jurisdictions, geographies and demographics.
At the moment, we are covering a fairly broad group of people across 35 sites in Australia and the US. The final trial would be bigger than that and broader.
We've confirmed with the FDA and with the European EMA that we only need to do one more pivotal trial to get to a marketing approval.
It is possible with the FDA that we may be able to get an accelerated approval if our results are really good, so we will be discussing that with the FDA. That's a long shot, but it's not out of the question.
That will be one of the things that we would do. We'd go back to the regulators immediately, particularly if the results are really positive. But, as I say, the planning is underway for that final Phase 3, and we will get straight into that.
Proactive: Plenty to look forward to. Thanks for the insight today, and we'll talk again very shortly.
