HOW ARE NEW DRUGS DEVELOPED? Durhane Wong-Rieger, PhD Consumer Advocare Network

OVERVIEW Examples of “innovative” and “incremental” discoveries What are steps from discovery to regulatory submission? What are likelihood of success and cost through the process?

I NCREMENTAL VERSUS BREAKTHROUGH INNOVATION Breakthrough innovation is characterized by first-in-class, or new therapies Examples include: Penicillin (first antibiotic); Insulin (first animal insulins); Thorazine (first anti-psychotic); first birth control pill “A breakthrough drug product is the first one to be sold in Canada that treats effectively a particular illness or address effectively a particular indication” (PMPRB)

F OLLOW - ON ( INCREMENTAL DEVELOPMENT ) Incremental Innovation is characterized by bit-by-bit, cumulative improvement Examples include: modern day antibiotics (4 days, one pill/day); newer insulin therapies, modern birth control pills, etc. Development of follow-on drugs occurs at the same time with that of the first-in-class Therapeutic value of follow-on drugs is reflected in the percentage of priority designations, inclusion in the clinical practice guidelines, and coverage in major formularies

N EW P RODUCT D EVELOPMENT : R ISKY AND E XPENSIVE Phase II 100–300 Patient Volunteers Used to Look for Efficacy and Side Effects Phase III 1,000–5,000 Patient Volunteers Used to Monitor Adverse Reactions to Long- term Use FDA Review Approval Additional Post-marketing Testing Phase I 20–80 Healthy Volunteers Used to Determine Safety and Dosage Preclinical Testing Laboratory and Animal Testing Preclinical Testing Laboratory and Animal Testing Discovery (2–10 Years) Discovery (2–10 Years) Years Compound Success Rates by Stage 5,000-10,000 Screened 250 Enter Preclinical Testing 5 Enter Clinical Testing 1 Approved by the FDA Net Cost: $1.3 billion invested over 15 years

C LINICAL T RIALS Conducted to determine the safety and efficacy of the new health technologies Many types exist Phases: Pre-clinical Phase I Phase II Phase III Phase IV (Post-Market)

M OST PRODUCTS THAT GET TO MARKET NEVER MAKE ENOUGH TO RECOUP R&D I NVESTMENT $0 New Products Grouped in Tenths According to Financial Success

M OVEMENT OF D RUG T HROUGH R EGULATORY S YSTEM Health Canada Common Drug ReviewProvincial Regulators Is the Drug Safe & Effective? Does the drug provide value? Do we have budget to fund the drug? PMPRB - Pricing