Novartis AG — Glivec EMA EPAR variation assessment report (EMEA/H/C/000406, 2001)
Novartis AG · 2001 · EMA EPAR variation assessment report · company profile →
Report summary
This report details a Type II variation application by Novartis for Glivec (imatinib) to extend its indication for pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) integrated with chemotherapy. The application included updates to the SmPC and Package Leaflet. Clinical efficacy data from studies STI571I2301 and STI571AIT07 demonstrated significantly improved event-free survival and overall survival rates compared to historical controls. While imatinib increased overall toxicity, it did not introduce new safety concerns, and death rates were lower than with chemotherapy alone. Safety concerns, including second malignancies and pregnancy tolerability, were addressed with proposed pharmacovigilance activities. The CHMP recommended approval for this extension of indication.
Key findings — cited to the page
| Daphnia sp. Reproduction Test NOEC for imatinib | 5.6 mg/L | Imatinib/Glivec · p.7 |
| fraction of imatinib metabolised to CGP74588 | 13% | · p.10 |
| DT50, whole system for imatinib | 83 -137 days | Imatinib/Glivec · p.6 |
| Activated Sludge, Respiration Inhibition Test EC10 for imatinib | 65.0 mg/L | Imatinib/Glivec · p.7 |
| imatinib clearance for Ph+ ALL patients compared to Ph+ CML | 9.7% less | · p.10 |
| fraction of imatinib metabolised to CGP74588 | 0.13 | · p.10 |
| Algae, Growth Inhibition Test NOEC for imatinib | 0.96 mg/L | Imatinib/Glivec · p.7 |
| DT90, whole system for imatinib | 309-552 days | Imatinib/Glivec · p.6 |
| imatinib dose range in CSTI571A2110 | 260 mg/m2 to 340 mg/m2 daily | CSTI571A2110 · p.8 |
| Fish, Early Life Stage Toxicity Test NOEC for imatinib | 10 mg/L | Imatinib/Glivec · p.7 |
| clearance for a subject with BSA=1.73 m2 | 9.06 L/h | · p.10 |
| recommended dose for paediatric Ph+ CML | 340 mg/m2 daily | Glivec · p.5 |
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 →