Unknown MAH — Akeega EMA EPAR variation assessment report (EMEA/H/C/005932, 2023)
Johnson & Johnson · 2023 · EMA EPAR variation assessment report · company profile →
Report summary
This report details a Type II variation application for Akeega (niraparib/abiraterone acetate) to extend its indication to adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) and BRCA1/2 mutations. The application is supported by the Phase 3 AMPLITUDE study, which compared niraparib plus abiraterone acetate and prednisone (nira+AAP) to placebo plus AAP. The study demonstrated a statistically significant improvement in radiographic progression-free survival (rPFS) for nira+AAP in patients with BRCA1/2 mutations. However, no clear benefit was observed in non-BRCA patients, who also experienced increased toxicity. Pharmacokinetic analyses showed higher niraparib exposure correlated with increased hematological toxicity. Safety data indicated significantly higher rates of adverse events, particularly hematological and vascular, in the nira+AAP arm. Consequently, the CHMP recommended approval of the variation, restricting the indication to mHSPC patients with BRCA1/2 mutations due to the lack of benefit and additive toxicity in the non-BRCA population. An updated Environmental Risk Assessment for abiraterone acetate also requires further studies.
Key findings — cited to the page
| Abiraterone Acetate NOEC (Daphnia sp. reproduction, 21d) | 0.47 μg L-1 | · p.13 |
| Niraparib tosylate monohydrate NOEC (Daphnia sp. Reproduction Test) | 320 μg L-1 | · p.16 |
| Grade 5 acute myocardial infarction events | 1 | · p.113 |
| Grade 5 arrhythmia events (sudden death) | 3 events | · p.114 |
| Grade 5 hepatotoxicity events | 1 | MAGNITUDE Cohort 1 · p.112 |
| Grade 4 or Grade 5 hepatotoxicity events | 0 | · p.113 |
| Grade 5 arrhythmia events (cardiac arrest) | 2 events | · p.114 |
| Grade 5 arrhythmia events (cardiorespiratory arrest) | 1 event | · p.114 |
| patients with Grade 3 cardiac failure without pre-existing risk factors | 1 participant | · p.113 |
| Grade 5 cardiac failure events | 1 patient | · p.113 |
| Grade 4 hepatotoxicity events | 1 | MAGNITUDE Cohort 1 · p.112 |
| Grade 5 arrhythmia events (sudden death) | 1 event | · p.114 |
Source: Johnson & Johnson ↗ · 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 Oncology library →