Phase III trials for experimental dementia-related psychosis treatment pimavanserin draw interest at AAIC; FDA begins consideration of the drug approval.
As many as half of the 45 million people worldwide who are living with Alzheimer’s will experience psychotic episodes, and that number is even higher among people living with some other forms of dementia. Psychosis is linked to a faster deterioration in dementia.
To date, there is no approved, safe, effective treatment for symptoms linked to dementia-related psychosis. Antipsychotics, while widely used (and alarmingly, widely misused), can lead to sedation, cause falls, and may double the speed at which brain function deteriorates. They have been linked to higher rates of hospitalization among people living with dementia, and when it comes to ICU delirium, they have been found to be ineffective. Patients, doctors and caregivers have long sought safer alternatives.
But there is growing optimism on the experimental drug front: A dementia symptoms treatment, pimavanserin, has yielded to “a robust reduction” in the severity of psychosis symptoms during a 12-week, open-label phase of a large-scale, international phase III relapse-prevention trial, according to a presentation at the Alzheimer’s Association International Conference this week. There, researchers from University of Exeter, in collaboration with ACADIA Pharmaceuticals, reported that the drug “substantially reduced” psychotic symptoms as well as reducing risk of relapse of those symptoms, compared to placebo in people with dementia.
In December 2019, Senior Director of Clinical Research at ACADIA Dr. Erin Foff discussed the trial with Being Patient: “The take-home here is that pimavanserin significantly reduced the risk of relapse by almost three fold,” she said. Further, according to Foff, more than twice the number the patients who received a placebo during the trial had a relapse into psychosis, compared to those who received the drug.
In contrast to anti-psychotics — the side-effect-laden current go-to for these symptoms — pimavanserin is said to work by blocking a specific nerve receptor (5HT2A) in the brain. Researchers report that this “can effectively reduce symptoms of psychosis in people with Alzheimer’s and other dementias, without evidence of some of the common side effects observed with other antipsychotics.”
In the latest development, the FDA is now considering pimavanserin — currently sold under the brand name Nuplazid and approved for treatment of Parkinson’s-related psychosis — be approved for dementia-related psychosis. Their decision is expected by April 3, 2021.
“Psychosis is a common and extremely disturbing symptom which has a severe impact on the lives of people affected by dementia,” Clive Ballard, Professor of Age-Related Diseases at the University of Exeter Medical School, who co-authored the research presented at AAIC. “We urgently need treatments that work.”
The trial enrolled 392 participants who were experiencing hallucinations and delusions linked to their dementia. Ballard’s team reported that pimavanserin had a consistent effect regardless of the subtype or severity of the underlying dementia. As Being Patient reported in late 2019, ACADIA is investigating whether it may also help treat schizophrenia, agitation and major depressive disorder.