1. CS-1 Regulatory Considerations: PDD Indication for Exelon ® (rivastigmine) Martina Struck, PhD Senior Associate Director Drug Regulatory Affairs Novartis Pharmaceuticals Corporation

2. CS-2 Exelon and PDD Indication  Parkinson’s disease dementia – Unmet medical need – Distinct disease entity  Exelon approved for dementia of Alzheimer’s type – Based on 2 well-controlled studies – 2.1 million patient yr of postmarketing experience  PDD is another type of cholinergic deficit dementia – PDD and AD both associated with cholinergic deficit Same mechanism of action

3. CS-3 Two Distinct Disorders With a Shared Cholinergic Deficit—Regulatory Considerations Supports separate indication of PDD Supports single- study approach for new indication of Exelon in PDD in addition to approved AD indication

4. CS-4 EXPRESS Study  Demonstration of effectiveness by a single study for a new use (EXPRESS in PDD), with independent substantiation from related study data (Exelon studies in AD) † – Purpose of Exelon therapy is to treat dementia symptoms due to cholinergic deficit  Adequate, well-controlled, multicenter study EXPRESS – Statistically very persuasive – Internal consistency across analysis populations and multiple endpoints from different domains † Guidance for Industry: Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products. May 1998, Clinical 6.

5. CS-5 Conclusion Exelon should be indicated for the treatment of mild to moderate dementia associated with Parkinson’s disease based on the adequate and well- controlled study EXPRESS