AR1001 Phase 3 trial in early Alzheimer’s to begin recruiting in UK
POLARIS-AD is already enrolling patients in US, South Korea
AriBio will soon start recruiting participants in the U.K. for the Phase 3 trial of AR1001 (mirodenafil), an investigational oral therapy for early Alzheimer’s disease.
This follows a positive opinion of the U.K. Medicines and Healthcare Products Regulatory Agency. The Polaris-AD trial (NCT05531526), which is enrolling patients at 67 sites in the U.S. and South Korea, will assess the safety and efficacy of AR1001 in people with early Alzheimer’s over about one year.
“Acceptance of the POLARIS-AD clinical study in the U.K. is another achievement in the development of AR1001. This acceptance represents the third region that will be actively screening and enrolling participants,” James Rock, AriBio’s chief clinical officer, said in a company press release. “AriBio will continue to expand the study into other regions where the regulatory and commercial markets are favorable for novel Alzheimer’s disease treatments.”
Alzheimer’s disease, a progressive neurodegenerative disorder, is the most common cause of dementia. Cognitive symptoms include memory loss, confusion, and personality skills.
Although its causes are largely unknown, the disease is marked by toxic proteins clumps in nerve cells, called amyloid plaques and tau neurofibrillary tangles, that lead to their death. In its early stages, the disease causes mild cognitive impairment and memory loss, though patients are typically still independent.
Studying AR1001 in Alzheimer’s
AR1001 is an oral inhibitor of phosphodiesterase-5 (PDE5), an enzyme that helps control blood flow and smooth muscle contractions by targeting a molecule called cGMP.
In preclinical studies, AR1001 diminished neuronal death and inflammation and restored synaptic plasticity, which is the ability of synapses to strengthen or weaken over time. Synapses are the junctions between nerve cells that allow them to communicate. Neurogenesis, that is, the formation of neurons in the brain, was also enhanced, according to the company.
A Phase 2 trial (NCT03625622) that assessed the safety and effectiveness of AR1001 in those with mild to moderate Alzheimer’s later showed it was generally safe and well tolerated at 10 and 30 mg daily doses over 52 weeks.
The treatment also reduced the blood levels of phosphorylated tau 181, a primary constituent of neurofibrillary tangles, and improved cognitive performance in participants with mild Alzheimer’s. Cognitive abilities were assessed using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog 13).
The results supported evaluating early Alzheimer’s patients in the POLARIS-AD trial. The study is enrolling patients, ages 55-90, with Alzheimer’s confirmed by a positive biomarker of brain amyloid disease. Eligible participants must also have symptoms of mild Alzheimer’s, such as problems with memory, planning, and organization, but can complete most daily tasks independently.
The participants will be randomly assigned to either AR1001 30 mg or a placebo once daily for 52 weeks. The study will test AR1001 in slowing Alzheimer’s progression through several cognitive and functional assessments.
The primary study goal is to assess changes in dementia using the Clinical Dementia Rating Scale–Sum of Boxes. Changes in cognitive function measured with ADAS-Cog 13, in the ability to perform activities of daily living due to cognitive decline, and in depression will also be investigated.
Safety and changes in biomarkers in blood and cerebrospinal fluid, which surrounds the brain and spinal cord, will also be evaluated, including p-Tau, beta-amyloid, and neurofilament light, a marker of nerve cell degeneration.
After the trial, patients will be able to enter an extension study, where all will receive AR1001 30 mg once daily for a year.
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