High Design Of Purest Gold A Critical History Of The Pharmaceutical Industry

High Design Of Purest Gold A Critical History Of The Pharmaceutical Industry Presented by: Graham Dutfield Date: 17 February2021 Understanding The Pharmaceutical Industry Co-Evolutionary Phenomenon - Science and technology - Business motivations, opportunities, practices - Regulatory frameworks - Law, especially relating to innovation and market exclusivities - Non-business advocacy groups and professional associations could be seen as forming a fifth element How Does The Industry Make Its Money? Motivations, Challenges, Responsive Practices, Social Consequence Motivations - Maximize shareholder value by making as much money from sales as possible employing all means possible, including: • Competitive research and development spending on discovery, testing, optimization and manufacturing; outsourcing and in-licensing • Marketing and pricing strategy to generate profits • Expanding use of approved medicines by seeking to add new indications Challenges - Commercial, Scientific, Regulatory And Behavioral - Need to satisfy shareholders and investors by providing sustainably-high income streams - Temporary nature of market exclusivity - generic market entry leading to lower prices - The 'low-hanging fruit' problem - arguably, results of cheaper and easier research have already been 'harvested' - Pharmaceutical research and development for new treatments expensive and risky massive failure rates, including at late-stage - Unpredictability and variability in patient responses (from 'exceptional responders' to fatal adverse drug reactions) - complex diseases lacking known and safe molecular targets - Few firms capable of internally integrating 'drug discovery to marketing approval' process on regular basis; and it's getting harder - Unharmonized regulations and intellectual property laws in overseas markets - Large corporations tend to be conservative, slow to change - small companies often spun out of universities more innovative, but lack money to get their products to market - The pursuit of profits not best motivation for radical discovery - hence continued dependence on curiosity- driven, non-profit research prevalent at universities - Lack of transparency makes it hard for companies to learn from other companies' failures - widespread duplication - hence massive wastage of time and money -"people don't 't publish their failures" (Prof Bounta, Oxford University) Responsive Practices - Building innovation networks involving universities, research institutions, funding bodies, and other company growing interest in 'open innovation' - Applying new technologies and methods including antibody drugs, artificial intelligence, Big Data collection management (what I call 'bio digital convergence') and - Tendency to focus on: • Variations on a theme' aiming at unambitious - but still potentially lucrative incremental innovations ' • Treatments for:  Reducing risk of future ill-health;  Non-communicable chronic and other non-lethal conditions requiring continuous consumption, but  Not for cures that entail temporary consumption • Medicines that maximize revenues in rich country markets taking advantage of regulatory norms and medical practices favoring 'medicalization' of existing conditions, or • Newly defined ones aided by 'pharmaceuticalization' phenomenon concentrating on those products most susceptible to strategic use of regulatory and property-related market exclusivities - Lifecycle management practices using intellectual property and regulatory exclusivities to • Extend effective monopolies • Shift patients onto new patented and branded products that provide marginal therapeutic advantages, while taking the old medicine out of production (sometimes referred to as 'line-extensions' or 'product-hopping') - Lobbying to harmonize patent and test data exclusivities worldwide - industry associations operating as political and quasi diplomatic actors Positive Social Consequences - More medicines for complex diseases like cancer - Shift towards personalized and precision medicine ("magic bullet") approaches better targeted towards the individual patient - More public-private partnerships and commercial collaborations across national frontiers - these should be more efficient and may encourage more open and transparent innovation Negative Social Consequences - Astronomically high prices on some medicine many of these publicly funded, and may not patent - Tendency in some countries to oversubscribe medicines and target medical conditions not necessarily requiring pharmaceutical response - this is wasteful, and may be harmful (e.g. Adverse drug reactions, addiction) - Marketing of classes of new drugs that may not be better than generic old ones (e.g. Ssris for mental health problems) - Neglect of therapeutic areas deemed unprofitable even though social welfare benefits would be enormous, e.g. Antibiotics, neglected tropical diseases - Anti-competitive behaviors such as much secondary patenting, certain strategic uses of trademarks covering pill shapes, colors and slogans - Regulatory 'gaming', i.e. Taking anti-social advantage of loopholes or weaknesses in regulatory regimes to acquire undue exclusivities, such as through orphan drug regulations - Harmful access and availability outcomes arising from effective lobbying of governments to adopt developed-country laws and regulations extending effective drug exclusivities The Glivec story - Novartis initially reluctant to market Glivec due to small numbers of CML patients - 2001 - US FDA & EMA approve Glivec as an orphan drug for treatment of Chronic Myeloid Leukemia. Subsequently priced in US at $2,000 to $2,400 per patient per month - 2003 - Glivec reaches $1 billion in annual sales. Yet orphan drug exclusivities not intended for blockbuster drugs - 2002-2006 Glivec approved for 8 additional rare (orphan) medical indications - And yet, the large corporations continue to under- invest in tyrosine kinase inhibitors are patents failing to incentivize innovation in the right areas? (Edwards et al 2011; Nicholas Lydon to author Sept. 2014) If Intellectual Property Rights Cannot Strike Balance Be Business Interests In Health Innovation And Social We Optimization, What Are The Alternatives? - Above all, this is a regulatory issue - intellectual property can be reformed, but this will not solve everything. We need to correct weaknesses in the whole regulatory system taking into account 1. Biomedical science's possibilities and limitations, and the impacts of new and emerging technologies and non-traditional market actors 2. The need for companies to make fair profits, 3. The regulatory regime, 4. The law governing the industry and dealing with market exclusivities and competition (i.e. Intellectual property). - These factors have a co-evolutionary relationship