Schizophrenia Treatment, Brexpiprazole, Seen to Ease Agitation in Alzheimer’s Patients in Phase 3 Trial

The schizophrenia medication Rexulti (brexpiprazole) reduced agitation in patients with Alzheimer’s disease, newly released data from two Phase 3 clinical trials of the drug show.

The studies highlight that efforts are ongoing to target symptoms — other than dementia itself — to improve the quality of life of Alzheimer’s patients and their loved ones.

The treatment, developed by Otsuka Pharmaceutical and Lundbeck, was also found safe in this patient group, with a similar side effects profile as was seen in earlier trials in other patient populations.

The two studies (NCT01862640 and NCT01922258) enrolled 700 patients diagnosed with probable Alzheimer’s disease and symptoms of agitation. The studies randomized patients to receive either brexpiprazole or a placebo, with neither study staff nor patients aware of the treatment — what’s known as a double-blind setup.

Both trials investigated brexpiprazole treatment over 12 weeks, but differed in their dosing schedules. The first trial treated patients with fixed doses of either 1 or 2 mg per day, while the other used a flexible range of doses, including 0.5 mg, 1 mg or 2 mg per day.

Both, however, focused on the primary outcome measure of lower agitation, assessed using the Cohen-Mansfield Agitation Inventory. Researchers also evaluated agitation using another tool: the Clinical Global Impression-Severity of Illness (CGI-S) score. Interestingly, the first trial showed a robust effect of the treatment in lessening agitation using the first scale, but not the second. The reverse scenario was seen in the other trial.

Researchers noted that data from different countries tended to vary. This, they said in a press release, may have been linked to “differing standards of care.” Data from clinical sites in Russia had notably lower differences between brexpiprazole and the placebo.

The most common adverse events in brexpiprazole-treated patients during the two trials were insomnia, agitation, and drowsiness, which appeared in between 3.3 % and 4.7% of brexpiprazole-treated patients. Placebo-treated patients had somewhat lower rates of these effects.

Otsuka and Lundbeck now plan to meet with regulatory authorities to discuss the data, which will also be presented at scientific meetings over the coming year.

Agitation is the term physicians use to describe symptoms of restlessness, significant emotional distress, aggressive behaviors, and irritability. It affects the majority of Alzheimer’s patients.

Brexpiprazole is currently approved for schizophrenia and as an adjunctive treatment of major depressive disorder (MDD) in the U.S. and for schizophrenia in Canada, under the brand name Rexulti. The European Medicines Agency (EMA) also recently accepted for review an application to approve the drug for use in the treatment of schizophrenia.

Although brexpiprazole is approved for these conditions, with five Phase 3 clinical trials backing the approvals, the exact mechanism making patients with these conditions improve eludes scientists.

The drug is known to act on several brain receptors for the neurotransmitters serotonin, dopamine, and norepinephrine.

While the drug is approved for schizophrenia, and evaluated in Alzheimer’s disease, brexpiprazole is not to be used with patients who have dementia-related psychosis. The U.S. prescription label holds a black box warning, stating that “elderly patients with dementia-related psychosis, treated with antipsychotic drugs, are at increased risk of death.”