Otsuka Holdings Co., Ltd. — Rxulti EMA EPAR public assessment report (EMEA/H/C/003841, 2018)
Otsuka Holdings Co., Ltd. · 2018 · EMA EPAR public assessment report · company profile →
Report summary
The EMA's assessment report for Otsuka's RXULTI (brexpiprazole) for adult schizophrenia treatment led to a positive marketing authorization opinion in May 2018. The report details the regulatory process, quality aspects, and extensive non-clinical and clinical data. Brexpiprazole's pharmacological profile involves serotonin and dopamine systems, with preclinical studies identifying potential risks like CNS depression and QT prolongation. Non-clinical safety showed some animal effects, but these were generally not clinically relevant. Pharmacokinetics revealed CYP2D6 and CYP3A4 metabolism, necessitating dose adjustments for certain patient populations. Clinical efficacy was demonstrated in short-term studies, with 2mg and 4mg doses showing superiority over placebo in PANSS and CGI-S scores, though not consistently across all trials. A long-term relapse prevention study significantly delayed relapse. Common adverse events included headache, akathisia, and weight gain. Safety concerns also encompassed extrapyramidal symptoms, metabolic changes, hyperprolactinemia, and QT prolongation. Despite these, the CHMP concluded a positive benefit-risk balance, recommending authorization.
Key findings — cited to the page
| Exposure margin for female reproduction NOAEL (AUC) | 0.3 | Brexpiprazole · p.47 |
| NOAEL for female reproduction | 0.3 mg/kg/day | Brexpiprazole · p.47 |
| NOAEL for female rat reproduction | 0.3 mg/kg/day | · p.37 |
| Exposure margin for female rat reproduction NOAEL (AUC) | 0.3 | · p.37 |
| Impact of patient exclusion from Arad, Romania site on efficacy reanalysis | no impact | brexpiprazole schizophrenia clinical program · Romania · p.14 |
| Impact of patient exclusion from Arad, Romania site on safety profile | remains unchanged | brexpiprazole schizophrenia clinical program · Romania · p.14 |
| Legal basis for Marketing Authorisation Application (MAA) | Article 3(2a) of Regulation (EC) No 726/2004 | RXULTI · European Union · p.14 |
| Marketing authorization application submission date | 28 February 2017 | RXULTI (brexpiprazole) · Europe · p.8 |
| Indication sought | treatment of schizophrenia in adult patients | RXULTI (brexpiprazole) · Europe · p.8 |
| CHMP positive opinion date for marketing authorization | 31 May 2018 | RXULTI (brexpiprazole) · Europe · p.9 |
| Brexpiprazole D3 receptor affinity (Ki) | 1.1 nM | · p.19 |
| Brexpiprazole molecular mass | 433.57 g/mol | · p.15 |
Source: Otsuka Holdings Co., Ltd. ↗ · License: EMA - reuse permitted with acknowledgement. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Psychiatry library →