Otsuka Holdings Co., Ltd. — Rexulti FDA Review (NDA205422, SUPPL 9, 2023)
Otsuka Holdings Co., Ltd. · 2023 · FDA Review (openFDA) · company profile →
Report summary
The FDA review recommends approval for Otsuka's Rexulti (brexpiprazole) for agitation associated with Alzheimer's dementia (AAD), citing substantial evidence from two positive Phase 3 trials (331-12-283 and 331-14-213). These studies demonstrated statistically significant improvements in the Cohen Mansfield Agitation Inventory (CMAI) total score at Week 12 for brexpiprazole (2-3 mg/day) versus placebo. While one study (331-12-284) did not meet its primary endpoint, post-hoc analyses showed efficacy in higher-dose subgroups. The drug addresses an unmet medical need, but concerns remain regarding the observed increased mortality risk in elderly patients with dementia-related psychosis, necessitating retention of the existing Boxed Warning. The safety profile was generally consistent with its known profile, with no new signals identified. An FDA Advisory Committee supported approval, finding benefits outweigh risks.
Key findings — cited to the page
| Percentage of subjects with comorbid irritability or aberrant motor behavior | 80 % | Study 331-12-283 · p.62 |
| Percentage of subjects with irritability/lability (Study 331-14-213) | 85% % | Study 331-14-213 · p.124 |
| Percentage of subjects with irritability (Study 331-14-213) | 85% % | Study 331-14-213 · p.125 |
| NPI-NH irritability/lability score LSMD | -0.94 | · p.144 |
| Mortality risk (IRR) for brexpiprazole vs placebo (all deaths across phase 3 studies) | 4.75 | · p.170 |
| Mortality risk (IRR) for brexpiprazole vs placebo (114-day sampling) | 4.16 | · p.170 |
| Agitation and irritability incidence (placebo group, Study 331-13-211) | 3.2 % | Study 331-13-211 · p.193 |
| Agitation and irritability incidence (brexpiprazole group, Study 331-13-211) | 3.4 % | Study 331-13-211 · p.193 |
| Recommended Indication | Treatment of agitation associated with Alzheimer’s dementia | Rexulti · p.2 |
| Application Type | sNDA | Rexulti · p.2 |
| Number of investigators with significant payments of other sorts | 1 | 331-14-213 · p.217 |
| Recommended Starting Dosage | 0.5 mg/day | Rexulti · p.2 |
Source: Otsuka Holdings Co., Ltd. ↗ · License: US Government public domain. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Psychiatry library →