Post Marketing Plan

Earl Sands, M.D. Vice President and Chief Medical Officer US Research and Development

Solvay Pharmaceuticals

Post Marketing Plan Agenda

RiskMAP PULZIUM Observational Study POST

RiskMAP Development
Inclusion of multiple stakeholders in US and EU
Physicians, nurses and pharmacists

Pretesting via user panels in US and EU

Iterative process; revisions made based on feedback

Objective: to provide the optimal benefit/risk balance for tedisamil by ensuring product use consistent with prescribing information
Minimizing risks Preserving benefits
3

RiskMAP Objectives
Align usage with the label Appropriate clinical setting (ECG monitoring and staff training) Appropriate patient selection Correct dose and administration Monitoring for a minimum of 2 hrs from the start of infusion and until QTc becomes normal

Risks to be Minimized
As with all antiarrhythmic drugs, tedisamil use has risks
Torsade de Pointes Bradycardia Hypotension

These risks can be minimized by addressing the potential contributory factors/causes:

Miscalculation/misadministration of dose

RiskMAP Tools
Labeling
Comprehensive, first line of risk communication Gender-specific, detailed height and weight-based dosing chart

Targeted education and outreach

A number of tools will be used in educating physicians and HCPs, which also have a reminder function and are therefore listed in the section below HCP website

Reminder systems
Physician checklist Infusion bag stickers Arrhythmia diagnostic guide QTc guide Dose guide and calculator Administration and monitoring guide 6

Selected RiskMAP Tools

Gender-specific Dosing Charts

Separate charts for males and females, which provide dose volume based on weight and height
Height Height

Weight

Weight

Outline of the Two-Bag Regimen

Infusion:
Bag 1
100 ml 10 min

Bag 2
100 ml 20 min

Step1: Infuse Bag 1 at 10 ml / min over 10 min Step 2: Infuse Bag 1 at 5 ml / min over 20 min

3 - way - cock

Pump

Multiplicity of RiskMAP Tools

Risk Minimizing Tool
Arrhythmi HCP admin Physicia Infusio a & HCP n n bag diagnostic Dose QTc monitoring websit checklist sticker guide guide guide guide e

Risk
Torsade de Pointes Ventricular tachycardia and bradycardia Miscalculation of dose by weight, height or gender Impaired electrolyte conditions, e.g. diarrhea

Drug-drug interactions and CYP2D6 inhibition

10

Post Marketing Plan

Earl Sands, M.D. Vice President and Chief Medical Officer US Research and Development

Solvay Pharmaceuticals

11

Post Marketing Plan Agenda

RiskMAP PULZIUM Observational Study POST

12

RiskMAP Development
Inclusion of multiple stakeholders in US and EU
Physicians, nurses and pharmacists

Pretesting via user panels in US and EU

Iterative process; revisions made based on feedback

Objective: to provide the optimal benefit/risk balance for tedisamil by ensuring product use consistent with prescribing information
Minimizing risks Preserving benefits
13

RiskMAP Objectives
Align usage with the label Appropriate clinical setting (ECG monitoring and staff training) Appropriate patient selection Correct dose and administration Monitoring for a minimum of 2 hrs from the start of infusion and until QTc becomes normal

14

Risks to be Minimized
As with all antiarrhythmic drugs, tedisamil use has risks
Torsade de Pointes Bradycardia Hypotension

These risks can be minimized by addressing the potential contributory factors/causes:

Miscalculation/misadministration of dose

15

RiskMAP Tools
Labeling
Comprehensive, first line of risk communication Gender-specific, detailed height and weight-based dosing chart

Targeted education and outreach

A number of tools will be used in educating physicians and HCPs, which also have a reminder function and are therefore listed in the section below HCP website

Reminder systems
Physician checklist Infusion bag stickers Arrhythmia diagnostic guide QTc guide Dose guide and calculator Administration and monitoring guide 16

Selected RiskMAP Tools

17

Gender-specific Dosing Charts

Separate charts for males and females, which provide dose volume based on weight and height
Height Height

Weight

Weight

18

Outline of the Two-Bag Regimen

Infusion:
Bag 1
100 ml 10 min

Bag 2
100 ml 20 min

Step1: Infuse Bag 1 at 10 ml / min over 10 min Step 2: Infuse Bag 1 at 5 ml / min over 20 min

3 - way - cock

Pump

19

Multiplicity of RiskMAP Tools

Risk Minimizing Tool
Arrhythmi HCP admin Physicia Infusio a & HCP n n bag diagnostic Dose QTc monitoring websit checklist sticker guide guide guide guide e

Risk
Torsade de Pointes Ventricular tachycardia and bradycardia Miscalculation of dose by weight, height or gender Impaired electrolyte conditions, e.g. diarrhea

Drug-drug interactions and CYP2D6 inhibition

20

PULZIUM Observational Study POST

A prospective observational study
1200 - 2000 patients demographic, prescribing and adverse event data 120 geographically diverse sites

The aim of the study would be to generate real-world benefit/risk data on tedisamil
detailed, real-time safety data evaluating safety and efficacy in ethnic minorities, i.e. African-Americans, Hispanics, etc. evaluating the success of the RiskMAP as a whole
21

PULZIUM Observational Study

The study would be under the auspices of an independent DSMB Data evaluated quarterly and every 300 treated patients

Periodic and real-time updates to FDA as necessary to meet the new REMS criteria*

*Source: Title II FDA Revitalization Act. Subtitle A Risk Evaluation and Mitigation Strategy (from http://help.senate.gov/minpress/2007_04_18 accessed on 9-12-07

22

Post Marketing Plan Conclusions

Targeted interventions to address known risks Key objective aligning usage with label Proactive, comprehensive program Built-in redundancy to improve effectiveness Consistent with existing clinical practice Sponsor is committed to evaluation and program revision, as needed Robust observational study to reinforce a positive benefit/risk profile
23