The first approved drug for agitation in Alzheimer’s patients has been approved by the US Food and Drug Administration, with Otsuka Pharmaceuticals’ brexpiprazole being given the nod last week.
The decision came after an advisory panel in April voted 9-1 that the company had enough data to identify the population in which benefits from the treatment outweigh its risks, reports Reuters.
Patients with Alzheimer’s sometimes show signs of extreme aggression or become restless and anxious as their brain loses its ability to negotiate with new stimulus.
US patients, currently, are calmed down using non-pharmacological strategies first, to be followed by off-label treatment with anti-psychotics and anti-depressants only in worse scenarios.
The approval of brexpiprazole is based on two late-stage studies, which showed significant improvement in calming agitated patients with Alzheimer’s, compared with a placebo.
Brexpiprazole, co-developed with Danish drugmaker Lundbeck, was previously approved to treat adults with major depressive disorder and schizophrenia.
The first study – Trial 213 – was designed to assess the safety, tolerability and efficacy of two fixed doses of brexpiprazole (2 mg/day or 3 mg/day) in the treatment of patients with agitation in Alzheimer's dementia.
The trial consisted of a continuous, 12-week double-blind treatment period with a 30-day follow-up, among 345 male and female patients, aged 55-90 (inclusive), with a diagnosis of probable Alzheimer’s disease, and meeting criteria of agitation as defined by the International Psychogeriatric Association (IPA).
The primary outcome was the change in the CMAI total score at week 12 for all patients treated with brexpiprazole vs those treated with placebo. The key secondary outcome was the change in the Clinical Global Impression – Severity of Illness (CGI-S) score, as related to symptoms of agitation.
The improvements from baseline on the primary endpoint of CMAI for patients receiving brexpiprazole or 2 mg/day or 3 mg/day were statistically greater than for those receiving placebo (p=0.0026). This result was supported by a statistically superior improvement on the key secondary endpoint of CGI-S, as related to agitation (p=0.0055).
Brexpiprazole was generally well tolerated, and no new safety signals were observed. The only treatment-emergent adverse event (TEAE) with more than 5% incidence in patients treated with brexpiprazole was headache (6.6% vs. 6.9% for placebo).
The following TEAEs occurred at an incidence of at least 2% in the brexpiprazole treatment group and greater than that of placebo: somnolence, nasopharyngitis, dizziness, diarrhoea, urinary tract infection, and asthenia.
There was one death observed in the 3 mg/day treatment group, assessed as not related to treatment by the investigator.
Full study results from the second trial were not available.
See more from MedicalBrief archives:
Alzheimer's: Benzodiazepine and related drugs raise mortality by 40%
Non-drug care the ‘first choice’ in dementia
Concern over FDA’s fast-track approval of Alzheimer’s drugs
Common meds linked to dementia risk