Esteve S A — Lysodren EMA EPAR variation assessment report (EMEA/H/C/000521, 2004)

Esteve S A · 2004 · EMA EPAR variation assessment report

Report summary

This report summarizes a Type II variation application for Lysodren (mitotane) to extend its indication to non-functional adrenal cortical carcinoma, based on the FIRM-ACT study. Although the indication extension was not approved, the CHMP updated the SmPC to include FIRM-ACT data, particularly regarding mitotane plasma levels and efficacy. The report also incorporates pharmacokinetic data from the LYS-001 study and safety information. Key safety updates include adding dysgeusia and dyspepsia as adverse reactions and emphasizing the monitoring of mitotane plasma levels, noting neurological toxicity above 20 mg/l. The FIRM-ACT study suggested improved disease control rates with levels ≥ 14 mg/l.

Key findings — cited to the page

Patients with treatment-related SAEs (high-dose regimen)	4 patients	PK FIRM ACT trial · p.18
Patients with treatment-related SAEs (low-dose regimen)	1 patient	PK FIRM ACT trial · p.18
Patients with plasma mitotane level >20 mg/l	8 patients	PK FIRM ACT trial · p.18
Patients with treatment-related gastrointestinal disorders (plasma mitotane level >20 mg/l)	3 patients	PK FIRM ACT trial · p.18
Orphan medicinal product designation date	12 June 2002	Lysodren · EU · p.2
Trial phase	III	FIRM-ACT · p.6
Target sample size	300 patients	FIRM-ACT · p.7
Actual enrolment	304 patients	FIRM-ACT · 12 countries · p.8
median progression-free survival	5.0 months	FIRM-ACT · p.9
median progression-free survival	2.1 months	FIRM-ACT · p.9
PFS Hazard Ratio	0.55	FIRM-ACT · p.9
Deaths in high dose regimen	4 patients	PK FIRM ACT trial · p.17

Source: Esteve S A ↗ · 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 →