Novartis AG — Zykadia EMA EPAR public assessment report (EMEA/H/C/003819, 2015)
Novartis AG · 2015 · EMA EPAR public assessment report · company profile →
Report summary
This report summarizes the EMA's assessment of Zykadia (ceritinib) for marketing authorization in ALK-positive advanced NSCLC, specifically for patients previously treated with crizotinib. Ceritinib is a potent ALK inhibitor, demonstrating anti-tumor activity in ALK-positive and crizotinib-resistant models. Non-clinical studies identified potential for QT prolongation and gastrointestinal/biliary toxicity. Clinical pharmacology detailed its pharmacokinetics and exposure-response relationships, emphasizing biomarker analysis. Efficacy data from Study X2101 and others showed promising response rates and progression-free survival, with a recommended dose of 750 mg daily. However, safety analysis revealed high rates of gastrointestinal adverse events, transaminase elevations, hepatotoxicity, and QT prolongation, often requiring dose reductions. Despite these safety concerns and limitations in some study designs, the benefit-risk balance supported conditional marketing authorization for previously treated patients.
Key findings — cited to the page
| Patients with abdominal pain (all grades) | 30.9 % | · p.82 |
| Patients with diarrhoea (all grades) | 81.7 % | · p.82 |
| Patients with vomiting (all grades) | 60.0 % | · p.82 |
| Patients with decreased appetite (all grades) | 34.9 % | · p.82 |
| Patients with grade 3-4 ALP increased | 4.4 % | · p.82 |
| Overall intracranial response rate (OIRR) | 45.5 % | registration trial · p.69 |
| Patients with grade 3-4 GGT increased | 6.9 % | · p.82 |
| Patients with nausea (all grades) | 77.7 % | · p.82 |
| Patients with increased ALT (all grades) | 39.2 % | · p.82 |
| Patients with increased AST (all grades) | 29.1 % | · p.82 |
| Patients with grade 3-4 diarrhoea | 5.0 % | · p.82 |
| Patients with fatigue (all grades) | 29.3 % | · p.82 |
Source: Novartis AG ↗ · 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 →