The last participant has completed the final visit in Actinogen Medical's pivotal Alzheimer's disease trial.
The final visit took place in the United States this week. The company told investors that topline results from the XanaMIA phase 2b/3 trial remain on track for November.
The trial tests the oral drug XANAMEM (emestedastat), designed to control elevated cortisol levels in the brain. Cortisol is often called the stress hormone, and high levels in the brain are associated with the onset and progression of Alzheimer's disease. The drug works by inhibiting an enzyme that makes cortisol inside brain cells. It leaves the cortisol produced by the adrenal glands alone, which the body needs to function normally.
XanaMIA enrolled 247 people with mild to moderate Alzheimer's disease. Forty-five per cent were recruited in Australia and 55 per cent in the United States. Participants were randomly assigned in equal numbers to take either XANAMEM 10 mg or a placebo once a day for 36 weeks, and neither they nor their doctors knew which they were receiving. After that phase, all participants can move into an extension study and receive the active drug for up to 25 months.
The main measure of success is the Clinical Dementia Rating Sum of Boxes, an internationally recognised scale of dementia severity.
To select participants for the trial, the company used a clinically validated blood test for a protein called pTau181. High levels of this protein select for patients whose disease is progressing more quickly. The company said this gives the trial a better chance of detecting a treatment effect within 36 weeks. It also mirrors the profile of patients in an earlier phase 2a study, where Actinogen reported a large treatment benefit for XANAMEM.
The participants resemble those in other trials of mild to moderate Alzheimer's disease. Their average age is 75, and 49 per cent are women. Two thirds carry the ApoE4 gene variant, the main genetic risk factor for the disease. They had an average pTau181 level of 2.6 pg/mL and an average dementia rating score of 4.3 points when they joined.
The trial has already passed review by an independent Data Monitoring Committee, which assessed both safety and whether the drug had any realistic prospect of working.
Actinogen chief medical officer Dr Dana Hilt said the focus now was on the data. "XANAMEM is a unique oral therapy with the potential to become a transformational treatment option for patients and their families living with Alzheimer's disease. Our key focus is to finalise high-quality data from the XanaMIA pivotal trial for release in November while planning streamlined pathways to the fastest possible regulatory approvals for XANAMEM."
The company has now tested XANAMEM in more than 500 volunteers and patients across eight clinical trials. In a separate phase 2a trial of 167 patients with moderate, treatment-resistant depression, reported in August 2024, the drug showed clinically and statistically significant benefits in depression symptoms.
