Otsuka Holdings Co., Ltd. — Rxulti EMA EPAR variation assessment report (EMEA/H/C/003841, 2018)
Otsuka Holdings Co., Ltd. · 2018 · EMA EPAR variation assessment report · company profile →
Report summary
Otsuka Holdings Co., Ltd. submitted a Type II variation for Rxulti (brexpiprazole) to extend its indication for treating schizophrenia in adolescents aged 13-17. The submission is supported by a comprehensive clinical development program, including Phase 1 and 3 trials, and pediatric extrapolation studies. These studies demonstrated comparable pharmacokinetic and exposure-response profiles between adolescents and adults, supporting the extrapolation of adult efficacy data. While a 6-week Phase 3 trial (331-10-234) showed a statistically significant but modest improvement in PANSS total score over placebo, particularly in the 15-17 age group, an ongoing long-term open-label trial (331-10-236) indicated sustained symptom improvement. Safety findings, including adverse events like nausea, headache, akathisia, weight gain, and metabolic changes, were generally consistent with adult populations. The CHMP recommended approval for the extended indication, acknowledging the efficacy and safety profile of brexpiprazole in this pediatric population.
Key findings — cited to the page
| Incidence of irritability in long-term open-label trials (all Brex) | 2.2 % | · p.95 |
| CGI-I response rates | 1.55 (95% CI 1.09,2.20) | Trial 331-10-234 · p.84 |
| Incidence of nausea in short-term controlled trials (all Brex) | 5.9 % | · p.93 |
| Treatment-emergent suicidal ideation | 15 subjects | · p.112 |
| Discontinuations due to AEs | 9 subjects | 331-10-236 · p.55 |
| Deaths | 0 | 331-10-236 · p.55 |
| Discontinuation due to lack of efficacy in long-term open-label trials | 2.2 % | · p.90 |
| Incidence of nausea in short-term controlled trials (Placebo) | 4.3 % | · p.93 |
| Incidence of akathisia in short-term controlled trials (all Brex) | 4.2 % | · p.93 |
| Incidence of akathisia in short-term controlled trials (Placebo) | 2.6 % | · p.93 |
| Incidence of headache in short-term controlled trials (all Brex) | 5.9 % | · p.94 |
| Baseline PANSS Total Score | 101.4 (14.7) | Trial 331-10-234 · p.82 |
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 →