Public Health and management: the challenges on access to medicines

Dr. Inthira Yamabhai

1 | Public health, innovation and intellectual property Overview

 Intellectual property (IP) and implications on access to medicine – Trade Related Aspect of Intellectual Property Rights (TRIPS) – TRIPS+ through trade agreements

 Sources of information

2 | Different forms of IP

Trademark: name under which product is marketed

Patent: compound, crystalline forms, process, method of use, etc

Protection of undisclosed data: clinical test data

Copyright: package insert

Design protection: packaging

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 There is nothing such as a worldwide !

 WIPO Patent Cooperation Treaty allows for worldwide filing, but applicant receives a bundle of national patents; same principle under European Patent Convention

 WTO TRIPS sets certain minimum standards: – Term: 20 years from filing data – Mandatory for all fields of technology – Criteria: novelty, inventive step, – Flexibilities: e.g. parallel importation and compulsory licensing

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One drug = one patent???

"…a key element of life cycle management strategies is to extent patent protection for as long as possible by filing secondary patents to keep generics off the market"

(Burdon and Sloper 2003) Sofosbuvir: Expiry without patent term extension(s) • Broad compound patent (Markush) Market 2024 • WO2005003147A2 Authorization US: 2013/14 • Compound patent on prodrug 2028 • WO2008121634A2 www.who.int/phi/impl ementation/ip_trade/ip • Crystalline forms _patent_landscapes/e n/ 2031 • WO2011123645A2

• Combination with ledipasvir 2032 • WO2013040492A

• Composition & dosage 2032 • WO2013082003A1 Incremental innovation vs life cycle management

Incremental advances for public health can include:

ƒƒ Combinations & new dosage forms with improved efficacy: co-formulation of antiretroviral drugs

ƒ Formulations with better product characteristics: vaccines stored in fridge rather than freezer

 New routes of delivery: tablets or nasal spray vs injections

 Paediatric formulations: dispersible flavored tablet of artemether-lumefantrine

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Granting patent in India: Imatinib case

 Novartis claims the drug is more easily absorbed into the blood that is enough of an improvement to warrant patent protection. India disagreed that Novartis had shown significantly increased efficacy and refused to grant a patent on Glivec (imatinib mesylate)

 Novartis file a case and India’s Supreme Court refused to grant a patent for Glivec, as it’s known in some countries

 India’s trade and industry minister, Anand Sharma, has defended the decision, and was quoted by Agence France-Presse as saying it was “absolutely justified under the law” and that India’s patent law “does not accept .”

8 | Estimated impact of evergreening

84% of patent applications during 2000-2010 are evergreening patents For 59 patented medicines, Thailand could have saved around 1,177 million THB (35 million USD) from 2000-2010

Source: Sutapak U et al (2011), Evergreening patent applications of pharmaceuticals and access to medicines

9 | Differential pricing

Sofosbuvir 12 weeks treatment course:

US: US$84,000 (reductions since Abbvie came to market)

UK: US$57,000

Egypt: US$900 (same price offered to public programme in Lao PDR; Mongolia)

Pakistan: US$1,620 (private sector)

10 | Where to draw the line?

Opposing trends:

Argentina, India and Philippines follow new approaches in the pharmaceutical area to limit secondary patents Brazil and South Africa consider similar rules (only new chemical compounds are patentable unless new form is more efficacious)

US through trade agreements endeavours to expand , e.g. secondary uses, methods of use and to prevent limitation of secondary patents

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Policy options

 Price controls: ‘Value-based pricing’; price/volume agreements; pay for performance; risk-sharing agreement / patient access schemes; reference pricing schemes…

 Differential pricing/price negotiations

 Voluntary licensing agreements

 Local production/import

 TRIPS flexibilities, including compulsory licenses

12 | Public health, innovation and intellectual property

Voluntary licenses HIV treatments (adults) INN Licensor Year Scope No countries Licsees

EFV MSD 2007 South Africa 1 (allows export to Several SSA) d4T BMS 2001 SSA, India. country list 50 Several

DDL BMS 2006 SSA; India; country list 50 Several

RAL MSD 2011 LIC; SSA 56 2 SQV Roche 2006 LDC; SSA 65 Several

DRV Tibotec (Janssen/J&J) 2012 Non-assert: LDC; SSA 65 1+non- License: India assert.

ZDV; ZDV/3TC ViiV Healthcare 2010 LDC; LIC; SSA 69 Several

TPV Boehringer-Ingelheim 2004/07 LIC; LDC; Africa, India 78 Several

NVP Boehringer-Ingelheim 2004/07 LIC; LDC; Africa; India 78 Several

DTG; DTG/ABC MPP: ViiV Healthcare 2014 Country list 73 (+ no patent MPP count.) EVG; QUAD MPP: Gilead Sciences 2011 Country list 100 Several TDF+FTC+EVG EVG13; QUAD| Public health,Gilead innovationSciences and2011 intellectual Country property list 100 + 9 semi- 4 TDF+FTC+EVG exclusive licenses for MICs ATV MPP: BMS 2013 Country list 110 (+ 34 no patent MPP count.) RPV/TDF/3TC or Tibotec (Janssen/J&J) 2011 Country list 112 5 FTC; RPV TDF Gilead Sciences 2006/11 Country list 112 Several

TDF; TAF; FTC MPP: Gilead Sciences 2011/14 Country list 112 Several Recent compulsory licenses & government use

Country Medicine Indication Measure Period Royalties Remarks Ecuador Abacavir+la HIV/AIDS Gov use 2012 5% of US Local prod. mivudine price adjusted by diff. in GDP Indonesia Seven HIV/AIDS; Gov use 2012 0.5% Local prod. products hepatitis India Sorafenib Cancer CL 2012 6% Local prod. Ecuador Ritonavir HIV/AIDS Gov use 2010 0.42% of US Import; local price prod. Thailand erlotinib; Cancer; Gov use 2006-2008 3-5% Import letrozole; heart docetaxel; disease; clopidogrel; HIV/AIDS lopinavir/rito navir Brazil Efavirenz HIV/AIDS Gov use 2007 1.5% Import & local prod.

Thailand14 | PublicEfavirenz health, innovation HIV/AIDS and intellectualGov use property 2006 0.5% Import Impact of CLs: Examples

 Brazil: – price reduction (from US$1.59 to US$0.43) – first import from India, followed by local production after two years (argument: lack of sufficient disclosure)  Ecuador: – price reduction (from US$1000 to US$800 initially; 50% reduction anticipated) – import from India (2010 CL); local production (2012 CL)  Thailand: – price reduction (3.4 to 6.4 fold for efavirenz and ritonavir) – GPO could initially not ensure local production of high quality products – import from India  India: – price reduction from Rs.280000 to 8880, plus free supply to 600 patients annually

Source: Kamp R, Doha Declaration on TRIPS & Public Health: Creating Legal Avenues for Access to Medicines, Trade and Public Health Workshop, 15 | 2016 New mega-RTAs

 Trans-Pacific Partnership (TPP)

 Transatlantic Trade and Investment Partnership (TTIP) (EU-US)

 Regional Comprehensive Economic Partnership (RCEP) (East Asia, 16 countries)

 Free Trade Area of the Asia-Pacific (FTAAP) (APEC, 21 countries)

16 | Size of new coming RTAs

Source: http://www.bilaterals.org/?businesses-believe-apec-s-free

17 | IP protection requirements: TRIP-Plus

 Expand scope of patentability – new forms of existing entities – new uses – new formulations and combinations, etc.  Data exclusivity (exclude use of registration data)  5+ years  New indication, formulation, method of administration  3+ years  Biological products8+ years  Extend patent term for regulatory delays  Patent linkage: Link drug registration and patent status  Criminal enforcement mechanisms for

18 | TRIP-Plus impedes the use of TRIP flexibilities

 IP Chapter Article 18.76: • Investment Chapter Annex 9 Special Requirements related (3B): expropriation to Border Measures – Philip Morris filed a case – German customs authorities against Australian government wrongfully seized a drug due to warnings on cigarette shipment of “Amoxicillin” on the packaging and removing suspicion that it infringed the branding from cigarette brand name “Amoxil” 4 weeks packaging its trademark and delay investment rights – Dutch customs authorities seized a shipment of abacavir sulfate while it was en route from India to Nigeria.

Sources: WTO, European Union and a Member State – Source: Seizure Of Generic Drugs in Transit, May 19, 2010. https://au.news.yahoo.com/thewest/a/29064155/tob Zarocostas, J., Brazil and India file complaint against acco-giant-sues-australia/ | EU19 over seizure of generic drugs, BMJ 2010 ;340:c2672

Sources of Information

 WHO-WIPO-WTO Study on “Promoting Access to Medical Technologies and Innovation (2013): www.wto.org/english/res_e/booksp_e/pamtiwhowipowtoweb13_e.pdf

 All you need to know about IP and health: http://www.who.int/phi/publications/category/en/

 Everything that is not happening in the WTO: www.bilaterals.org

 WTO RTA database: http://rtais.wto.org

20 | Public health, innovation and intellectual property 20 Sources of Information

 World Trade Report 2011: The WTO and Preferential Trade Agreements: http://www.wto.org/english/res_e/publications_e/wtr11_e. htm

 Texts of RTAs: www.ustr.gov www.efta.int http://ec.europa.eu/enterprise/policies/international/facili tating-trade/free-trade/index_en.htm

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Thank you

Dr Peter Beyer Senior Advisor World Health Organization [email protected] Tel. +41-22-791 25 07

Dr Inthira Yamabhai Technical officer [email protected]

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