COMMONALITIES ACROSS TREATMENTS AND DISEASES A BRIEF OVERVIEW

COMMONALITIES ACROSS TREATMENTS AND DISEASES: A BRIEF OVERVIEW Dr Andrew Hill Department of Translational Medicine, University of Liverpool, UK World AIDS Conference, Amsterdam July 24 th 2018

Costs versus prices of medicines There are many cases of massive overcharging – drugs sold for 100 to 1000 times more than they cost to make. Some of these drugs are generics. Almost all medicines are very cheap to manufacture. Prices should be checked by country, to check on overcharging. Lists of drug costs and prices should be updated every two years, in parallel with updates of the EML. Expand analysis to include new drugs and more countries. http: //gh. bmj. com/content/3/1/e 000571 2

Active Pharmaceutical Ingredient Raw drug substance Database www. indiainfodrive. com shows exports of API from India to other countries, with costs per kilogram of API, for many drugs 3

1 year’s supply of pomalidomide (Imnovid): 1. 0 g To treat multiple myeloma Cost in the UK (NHS): £ 115, 809 per year (Celgene) Cost of production: £ 100 per year

Lowest available price for Imatinib (400 mg) in selected countries $ 120, 000 $ 106, 322 Imatinib (Gleevec) US price: $106, 322 Cost price: $180 $ 80, 000 $ 60, 000 $ 35, 216 $ 34, 482 $ 31, 867 $ 40, 000 $ 28, 675 $ 20, 877 $ 20, 000 $ 8, 370 $ 8, 192 $ 790 ut h pr ice es tim at e ic) Ge ne r a( in im um In di Ge il ( az Br (N ov ne ar ric ) tis ) ) ss ia Ru Th ai la nd (N (N ov a rti s s) ) (N ov ar tis ) tis UK Fr an ce Sp ai n (N ov ar er rti $ 180 M Af ric a( No va US A (N ov s/ Ge n ar tis ic) ) $0 So Price per year (USD) $ 100, 000 Hill et al: Target prices for mass production of Tyrosine Kinase Inhibitors: http: //bmjopen. bmj. com/content/6/1/e 009586. full

Cost-based generic price of dolutegravir (52 weeks)

Dolutegravir price versus Gross Domestic Product per capita Upper Middle-income countries References: Prices - National drug price database, drug reimbursement authorities, WHO GPRM database; GDP per capita (2016): World Bank

Widespread access to generics When patents have expired, drugs should be available worldwide, at close to the cost of production However, few national health services know these costs Lower costs for generics could drive down patented drug prices in the same therapeutic area Health and Finance Ministers would be amazed at the savings they could make, or the extra people they could treat, if they could achieve these low prices for drugs.

10000 9000 8000 Price 7000 Patent expiry Drug prices after patent expir Schematic showing price rises – what should happen 6000 5000 Reference: Hill et al, BMJ Open 2015 4000 http: //bmjopen. bmj. com/content/6/1/e 009586. full 3000 2000 Generic price Cost price 1000 0 1996 2001 Time 2006 (Year) 2011 2016 2021

Generics can be cheap worldwide

Generic TDF/3 TC/EFV should also be available for prices close to $90/year, in any country Cipla – Tenvir-EM Mylan – Revcovir-EM

Prices and costs of drugs to treat HIV, HBV, HCV and TB DRUG USA PRICE GLOBAL ESTIMATED LOWEST PRICE COST PATENT EXPIRY (US) TDF/3 TC/EFV $28, 204* $107 $82 Generic TDF/FTC $17, 258 $67 $54 Generic Entecavir $5, 915 $409 $36 Generic SOF+LDV $91, 207 $307 $79 2028 -2032 SOF+DCV TB: RHZE $142, 710 $945 $78 $27 $47 2028 -2031 $38 Generic *for TDF/FTC/EFV; HCV – per 12 -week course, TB – per 6 month course, HIV and HBV – per year. Patent expiries from US FDA Orange Book (oral dosing)

10000 9000 8000 Price 7000 Patent expiry Drug prices after patent expir – what price can happen Schematic showing rises 6000 5000 4000 New generic company takes control of Production, raises prices 3000 2000 1000 0 1996 Cost of production 2001 Time 2006 (Year) 2011 2016 2021

Prices of drugs to treat Opportunistic infections of AIDS South African price Indian price Amphotericin B + fluconazole $13, 983 $988 Valganciclovir $5973 $987 Clarythromycin + Disseminated MAI ethambutol $332 $35 MDR TB $415 $25 Disease Drugs Cryptococcal meningitis CMV retinitis Linezolid Prices per course or per month (linezolid)

Drug prices after patent expir – what can also happen 10000 9000 8000 Price 7000 Patent expiry Schematic showing price rises Generic companies never lower prices close to costs of production 6000 5000 4000 3000 Reference: Hill et al BMJ Open 2017: 7; e 011965 2000 1000 0 1996 Cost of production 2001 Time 2006 (Year) 2011 2016 2021

Insulin for diabetes Discovered in 1923 Global market: $28 billion Cost price: $1 per vial Sold for up to $240 per vial

If drug prices were lower, could pharmaceutical companies still afford to do R&D? 19

HIV drug sales, 2002 -2016 (in USD billions) 30 Billions 25 20 $200 billion in HIV drug sales 2002 -2016 15 10 5 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Gilead GSK BMS Abbvie/Abbott J&J Merck

Gilead sales and profits Cumulative sales of Sovaldi & Harvoni to 2 Q 2018: $55 billion Profits in 2015: $18 billion Reference: Gilead quarterly product sales summaries

Pharma profits and tax avoidance Main tax havens: Bermuda, Cayman Islands, BVI, Bahamas, Luxembourg, Ireland Company Profits held offshore US Taxes Avoided Pfizer $69 billion $20 billion Merck $57 billion $16 billion Johnson & Johnson $51 billion $14 billion Amgen $26 billion $9 billion Abbott $24 billion $7 billion BMS $24 billion $7 billion Source: Citizens for Tax Justice, 2016. http: //gormanandjoneslaw. com/offshore-tax-havens/ 22 http: //america. aljazeera. com/articles/2015/3/12/obama-gambit-for-corporate-cayman-cash. html

Universal Access to Essential Medicines 1. Show countries how much they could save from buying all generic drugs at close to cost prices 2. Maximise use of generics, in national treatment campaigns. Identify high quality generic suppliers 3. Re-evaluate the cost-effectiveness of all patented drugs, versus cheap generic alternatives – this should lead to a cascade of price reductions 4. If companies refuse to lower prices, use TRIPS flexibilities to ensure access – compulsory licenses, personal importation, patent challenges.