LYSOSAFE

1. LYSOSAFE

2. What is Lysosafe? • A huge evolution in the treatment of Adrenal Cortical Carcinoma in Europe • A free of charge service associated with the use of HRA Pharma’s Lysodren (mitotane, 500 mg tablets) • The benefit of mitotane plasma level testing for all patients in Europe treated with Lysodren • The possibility to obtain mitotane plasma level results within 10 days • An answer to the recurrent demand from European Lysodren prescribers

3. Lysodren and Lysosafe

4. Lysodren (mitotane, 500mg tablets) • Therapeutic indication: • Symptomatic treatment of advanced (unresectable, metastatic or relapsed) adrenal cortical carcinoma. The effect of Lysodren on non-functional adrenal cortical carcinoma is not established • Dosage and method of administration • Treatment should be initiated by a suitably experienced specialist • Treatment should be started with 2-3 g of Lysodren per day and increased stepwise until mitotane plasma levels reaches the therapeutic window (mitotane plasma level between 14 and 20 mg/l) with acceptable safety, which usually corresponds to a cumulative dose of 75 g. The total daily dose may be divided in two or three doses according to patient’s convenience, and should be preferably taken during meals containing fat-rich food • If serious adverse reactions occur, such as neurotoxicity, treatment with mitotane may need to be transiently interrupted. In case of mild toxicity, dosage should be reduced until the maximum tolerated dosage is attained

5. Lysosafe: multiple advantages for the patient and for the prescriber Lysosafe is a valuable tool for Lysodren prescribers, which assists in: • Adapting the patient’s Lysodren dose • Obtaining plasma mitotane level results in less than 10 days • Optimizing the efficacy of treatment with Lysodren

6. Lysosafe: essential tool Why is it necessary to monitor the mitotane plasma level during treatment with Lysodren? • To reach the therapeutic level (14 to 20 mg/l) • To reduce risk of undesirable effects (above 20mg/l) • To adapt the dose in specific patient populations: • Elderly, • Paediatric, or • Patients with renal or liver impairment

7. Lysosafe and pharmacovigilance Lysodren has a narrow therapeutic window, which lies between 14 mg/l and 20mg/l. Plasma levels higher than 20 mg/l may be associated with severe undesirable effects such as neurological toxicity • In accordance with the European Union regulatory requirements, HRA Pharma is required to collect all information regarding adverse events during treatment with Lysodren. Therefore HRA Pharma works in partnership with European clinicians to enhance the likely clinical benefit to the patient and clinician • In this context, when HRA Pharma’s Pharmacovigilance department is made aware of mitotane plasma levels greater than 20 mg/L, the clinician will be contacted directly • In the event of a patient presenting any adverse reaction the clinician should spontaneously contact HRA Pharma’sPharmacovigilance departmentby email: pharmacovigilance@hra-pharma.com, by fax: +33 1 42 77 03 52, or by phone: +33 1 40 33 11 30 to offer you a close follow-up • All information concerning suspected adverse reactions reported to HRA Pharma is then collected, documented, evaluated and recorded to improve knowledge of Lysodren

8. The parties involved in Lysosafe

9. Lysosafe: 3 key players all linked Lysosafe member A unique logistical partner A unique technical partner

10. A unique technical partner: • One of the largest Contract Research Organizations (CRO) in the world • Experienced project teams perform all analyses and studies • Atlanbio provides: • A high standard of scientific and bioanalytical services • A tailor made service to meet Lysosafe requirements • A team dedicated to Lysosafe using: • A unique centralized bioanalytical center • A unique and approved GC/MS (Gas Chromatography / Mass Spectometry) analysis method

11. A unique logistical partner: • The world’s leading express and logistics company • Lysosafe uses DHL’s World Medical Express service • High quality service via dedicated and specialized networks • Outstanding security with fulfillment of stringent regulatory requirements • Total control of the sample inventory and delivery process • Lysosafe benefits from DHL’s healthcare skills and experience