1. The DMO: Improving the Quality, Quickness and Quantity of Access to Alzheimer’s Disease Treatments By Whitney Davis 2011 WISE Intern University of Arkansas August 4, 2011

2. US Food and Drug Administration  FD&C Act passed in 1938 (safety)  Kefauver Harris Amendment in 1962 (efficacy)  Only entity legally responsible for approval of:  Medical devices, food, vaccines, veterinary treatments, radiation-emitting products, cosmetics, tobacco products, and drugs for all diseases, conditions, and products

3. Drugs Food Medical Devices Cosmetics Vet Products Vaccines Tobacco Products Radiation -emitting Products Dietary Supplements Infant Formulas Biologics Animal Feed Tanning Products Food Additives Blood Products Hepatitis Xray Systems HIV Breast Implants Defibrillator Addison’s Disease Cancer Wheel - chairs Catheter Hearing Aids Lou Gehrig’s MS Small- pox Imaging Systems Heart Monitors Cardiov ascular Disease Asthma Fertility Drugs Arthritis West Nile Virus Pacem akers SARS Artificial Hearts Lupus Heart Valves Influenza Alzheimer’s Disease

4. Overview: Alzheimer’s Disease  A progressive, degenerative disorder that attacks the brain's nerve cells, or neurons, resulting in behavioral changes and loss of memory, thinking, and language skills  6 th Leading Cause of Death in US  Average life expectancy after diagnosis is 8 years  Age is greatest risk factor  5.4 million people live with AD

5. Economic Impact of AD  Total cost for care: $183 billion  Annual cost of care: $18,500 - $36,000  Unpaid care in 2010: 14.9 million family & friends provided 17 billion hours = $202.6 billion  Costs US businesses $60 billion a year  Medicare payments are 3x higher  Medicaid payments are 9x higher

6. Current FDA Challenges To Develop A Drug: o Average Time: 10 years o Average Cost: $1 billion o User Fee: $1 million Safety Efficacy Safety & Efficacy Phase IV: Safety & Efficacy

7. Current AD Treatments Name:Phase:Use:Success:Completed: Methylene Blue 2 Prevent aggregati on of tau protein fibers PositiveYes PBT-22 Prevent aggregati on of beta- amyloid into plaques PositiveYes Solanezumab3 Lab- produced antibody to beta- amyloid N/ANo

8. Government Reactions  Fast Track  product must concern a serious or life-threatening condition and has to have potential to address an unmet medical need  allows manufacturers to submit sections of their NDA to the FDA as they are ready rather than submitting a complete application at one time  can meet with FDA so that components of clinical study design and presentation can be clearly defined  Accelerated Track  accelerates approval of a drug that provides a “meaningful therapeutic benefit…over existing treatments”  approval based ongoing clinical trials  instead of survival rates or disease progression, a “surrogate endpoint that is reasonably likely…to predict clinical benefit” is used  Priority Review  Intended for products believed to address unmet needs  shortens the approval decision from 10 months to 6 months

9. Results o Manufacturers have requested Fast Track designation for 569 drugs since the Fast Track program was set into law o 74.5% of those drug requests were granted o Of products with Fast Track designation, 10.6% of the drugs were approved

10. Current FDA Challenges  Economically Unmanageable Amount of Responsibility  Single Option for Drug Developers  Inefficient In Accurately Perceiving Demand  Can’t specify around a particular disease  Blanket “safety” definition

11. Economically Unmanageable Amount of Responsibility o Needs funds to match human resources & facilities to responsibility o Financial resources get spread thin o More funds with little production Economically Unmanageable Amount of Responsibility

12. Single Option  Highly restricted early access except through clinical trials  No personalization  No incentive to improve:  Trials  Cost  Access

13. Inefficient In Accurately Perceiving Demand  Revenue not directly affected by demand  Revenue always guaranteed

14. The DMO: Direct Market Option  After submitting an IND, drug developer will have option to pursue DMO parallel to the conventional FDA approval track  Can legally gain approval by free market organization  Only requirement: drug developer must enter into a contract with organization in which the drug developer possesses liability for unknown or unlisted adverse effects  Drug developer can run clinical trials set under different conditions and methods by a free market organization  Organization responsible for:  post-market research  fining the company for false labeling and advertising as seen fit.

15. Open More Options  More approved drugs  Better specialize  tradeoff of risk vs. benefit  potentially earlier access to drugs  More competition to meet demand  more efficient trials  faster access  cheaper drugs  cheaper user fees

16. More Accurately Meet Demand  Revenue directly affected by demand  Can specialize & require less resources  Focus funds for better quality

17. Questions? Whitney Davis IEEE – WISE Intern wxd003@uark.edu