VIEWS: 6 PAGES: 28 POSTED ON: 12/3/2009
25 Years of Biotechnology – Has It Met Its Promise? Gilad S. Gordon, MD, MBA Disclosures Consultant to: – Allos Therapeutics – Array BioPharma – Attenuon – GlobeImmune – Intarcia – Kinex – MetaBasis – OSI – QLT – Quark Pharmaceuticals 25 Years of Biotechnology – Has It Met Its Promise? Yes – Remarkable strides since human insulin approved in 1982 – Cured some diseases – Improved quality of life for many – Clearly a mature industry with hundreds of drug approvals No – No clear drug products from Human Genome Project – No clear therapeutic path to individual genomic based pharmacotherapy Biotechnology History 1953 – Structure of DNA defined – My parents get married 1957 – Lord Todd wins Nobel Prize “for his work on nucleotides and nucleotide co-enzymes” – I am born 1962 – Watson and Crick win Nobel Prize – I enter Kindergarten 1974 – Boyer and Cohen demonstrate the expression of a foreign gene in bacteria – I apply to college 1976 – Genentech, first biotech company is formed – Dr. Bill Haseltine is assigned as my tutor, I go pre-med 1978 – First successful laboratory production of recombinant human insulin – I take the MCATs Biotechnology History 1980 – Genentech goes public 1980 – First human test of recombinant insulin – I begin second year of medical school 1982 – Human insulin approved by FDA and marketed by Eli Lilly under license from Genentech – Senior year - I undertake studies on intra-nasal insulin with future Dean Dr. Jeffrey Flier 1983 – First monoclonal antibody test approved for testing for Chlamydia Trachomatis – We graduate Harvard Medical School! Biotechnology History 1985 – Genentech receives FDA approval for human growth hormone – first drug to be marketed by biotechnology company 1985 – Polymerase Chain Reaction (PCR) technology developed 1986 – Chiron receives FDA license for Hepatitis B vaccine – first recombinant vaccine 1986 – Muromonab-CD3 receives FDA approval for reversal of acute kidney transplant rejection – first monoclonal antibody approved for therapy – I finish residency in Internal Medicine Biotechnology history 1990 – First gene therapy for ADA deficiency 1990 – Jurassic Park published – public aware of risks 1991 – UCSF and Stanford earn $40 million from patents – changes way universities look at biotechnology 1991 – Alglucerase approved to treat Gaucher’s disease 1997 – First cloned sheep - Dolly 1997 – Rituximab receives FDA approval – first antibody based treatment for cancer (non-Hodgkin’s Lymphoma) 2000 – Human Genome mapped Biotechnology Companies (2006) Companies United States Worldwide Public 336 710 Total 1452 4275 Revenue* $55.4 B $73.5 B Net Loss $3.5 B $5.4 B Research and Development** $22.8 B $27.8 B # employees 130,600 190,500 *52 companies are profitable **For comparison: 2006 NIH Budget - $28.7 B Ernst & Young, 2007 Biotechnology today 2000 3 biotech product categories with over $1 billion in sales out of 36 total products with over $1B in sales 2006 18 biotech product categories with over $ 1 billion per year in sales out of 101 total products with over $1B in sales 10 biotech product categories with over $2 billion in sales out of 36 total products with over $2B in sales New Biotech Drug and Vaccine Approvals/ New Indication Approvals by Year New Biotech Drug and Vaccine Approvals/ New Indication Approvals by Year Bio, 2007 Top 10 Biotechnology Proteins Drug 2006 Sales Human insulins (diabetes)* $7.8 B Epoetin alpha (anemia)* $6.1 B Etanercept (arthritis) $4.4 B Darbopoetin (anemia)* $4.1 B Rituximab (NHL) $3.9 B Infliximab (Crohn’s, arthritis) $3.6 B Trastuzumab (breast cancer) $3.1 B PEG-filgrastim (neutropenia)* $2.7 B Bevacizumab (colon cancer) $2.4 B Adalimumab (arthritis) $2.0 B * ”Replacement therapy” Ernst & Young, 2007 Major Challenges Complexity and costs of clinical research FDA policies Pricing Financing Phases of Clinical Research Phase I – 50-100 patients – First in Man – Dose escalation – Define Maximum Tolerated Dose Phase II – 200-1000 patients – Early efficacy trials – Define therapeutic dose – Define study population Phases of Clinical Research Phase III – 500-5000 patients – Large clinical trials – Define safety and efficacy in target population – Define limitations of drug Phase IV – thousands of patients – Post-approval – Better define safety – Identify other target populations Clinical Research Timelines and Costs Overall costs – discovery to approval – Time: 4-14 years – Costs: $30-$200 million Over $800 if amortize costs of failed drugs – Number of patients: Minimum 500 for rare disease or unmet medical need 5,000 for drug for common disease, i.e. arthritis Over 60,000 for recent vaccine for RSV Clinical Research Ongoing challenges – Access to patients – Access to investigators – Availability of research personnel – Location of research United States Developed world Under-developed world FDA Policies Overall, fewer new drug approvals Balance of off-label use vs. restriction on off- label use Balance of safety vs. demand for new therapeutics – Currently weighted towards safety – Increased need for post-marketing safety studies – Demand for increased size of trials to demonstrate safety What is role of generic proteins, i.e. bio-similars? Costs of Treatment of Colon Cancer 1996 – Total costs of drugs: $500 – Expected median survival: 11 months 2007 – Total costs of drugs: $250,000 – Expected median survival: 24 months IS TREATMENT WORTH $20,000 PER ADDITIONAL MONTH OF LIFE? Ernst & Young 2007 Pricing What is a fair price? – Company perspective “Appropriate” return on investment to investors Assure future investments in the field Comparable pricing to “similar” products Favorable cost-effectiveness analyses Drug costs are still less than 10% of total costs of healthcare – Public health perspective Can payers afford $500 to $35,000 (Eculizumab for PNH) per month? Is this price-gauging? Should prices be based on “cost of goods”? What is the “value” of the drugs? Why are prices lower in other countries? Pricing - Response of Payers Governments – develop cost-effectiveness guidelines for drug pricing approval – UK – Rejected use of bortezomib, bevacizumab, and cetuximab based on price – Australia – Rejected use of Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant based on price Local Payers – Strict criteria on who gets drug Insurance companies – Increase co-pays Individuals – Decision to forego therapy Overall, should there be a “pricing policy” and what would be its implications? Financing Sources Government Venture capital Partnerships Public markets Additional Challenges Basic research Pre-clinical research Intellectual property Pharmacogenomics Individual therapeutics Early Stage Research Basic research – Harder to justify in corporate world – role of NIH – Who will fund? Pre-clinical research – Most active area of research – Need to define more appropriate pre-clinical efficacy models – Need to define more appropriate toxicology models Intellectual Property How to protect Intellectual Property? – Role of Universities – Changing rules – “first to file” vs. “first to invent” – Value of IP in developing countries Pharmacogenomics How to integrate human genome knowledge? – How to translate findings of the human genome into population based therapeutics? How to determine if specific DNA mutations cause disease? How to develop therapy for different mutations in different genes which cause the “same” disease? How to treat different mutations in the same disease-causing gene? How to develop specific therapeutics for specific DNA mutations? – Population-based genotype databases? Critical to understand disease, the effect of therapeutics, and the safety of therapeutics? How can one preserve confidentiality in age of “insurance discrimination”? Individual Therapeutics How to develop individual therapeutics? – Can genotype differences predict response to a therapeutic? i.e different responses amongst African-Americans to isosorbide dinitrate/hydralazine for heart failure – How to develop drugs for individual patients The ultimate holy-grail of medicine! Requires change in paradigm of FDA review – Are there valid “pre-clinical” models that can be used? – Need to focus on individual efficacy vs. population based safety and efficacy 25 Years of Biotechnology From Human Insulin to Today….…. Industry is certainly mature Hundreds of drugs approved Many patients have benefited Challenges remain Overall – promise of the new technology of 1983 has largely been met and even exceeded! The Future…………….
"25 Years of Biotechnology – Has"