1 Increasing antiretroviral treatment access in developing

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Increasing antiretroviral treatment access in developing countries Malam Aboubakar Perrine Dieusaert Jean-Luc Hitimana

A global view of HIV infection worldwide 16 000 40 million 95% 2, 7 million 2 million. More than 28% 3

Treatment coverage worldwide 6% 84% 19% 5% 2 -5% 7% 4

AIDS, a real weapon of mass destruction 75% 5

- Treatment 1987 : 1 st Nucleoside Reverse transcriptase Inhibitors (AZT) 1989 -1994 : New Reverse transcriptase Inhibitors (d 4 T, 3 TC) 1995 : Bitherapy 1996 : Protease Inhibitors (Kaletra) and tritherapy 1998 -1999 : Non nucleoside Reverse transcriptase Inhibitors ( Viramune, Efavirenz, Sustiva ) 2002 : Nucleotide Reverse transcriptase Inhibitors (Viread) 2003 : Entry Inhibitors (Fuzeon) 2006 : Tritherapy once a day (Atripla = Sustiva+Emtriva+Viread) 7

- Treatment in developed countries : DOT-HAART (Directly Observed Therapy of Highly-Active Anti. Retroviral Treatment) - Example in South Africa : first line regimen : d 4 T, 3 TC and Efavirenz second line regimen : AZT, dd. I and Kaletra Old medicines Irrational use of treatment Opportunistic infections treatment 8

CD 4 below 350 or viral loads greater than 30, 000 copies/ml of plasma. Clinical signs and symptoms : Opportunistic infections, chronic diarrhea, weight loss, neurologic complications, lowering of red/white blood cells counts… 9

- According to the WHO (World Health Organization), in developed countries, a course of 1 year’s treatment costs the equivalence of 4 or 6 months’ salary. - In developing countries, it would consume 30 years income. 10

The WHO’s 3*5 Program : 3 M people access in 2005 6 M people infected with HIV in the developing world, of which only 400, 000 had access. RESULT: « Missing the target » (1, 3 M in 2005, december) 11

- International Institutions The World Health Organization (WHO) - Published treatment guidelines - Prequalification process - Essential medicines list - National Institutions A drug had to be registered in each country A drug could be brought through an import waiver 12

- Funding The main sources of funding in 2003 were : The Global Fund The President’s Emergency Plan for AIDS Relief (PEPFAR) - Intellectual Property The standards of patent protection varied widely around the world. The 1986 -1994 of multilateral trade negociations resulted in the Agreement on Trade-Related Aspects of Intellectual Property Rights ( TRIPS) 13

The TRIPS agreement Harmonizes the patent rights • Patent protection for pharmaceutical products • 20 years protection TRIPS provided for exceptions • Compulsory Licence • Parallel Importation 14

- Distribution No physical presence No local contact No in-house expertise. - Public Perception Aids activist groups, health care providers and some governments are strong critics of pharmaceutical companies. 15

Let’s try to take the Industries’ state of mind… What are the positive and risky points? Positive publicity for the company BUT… Reputational risk Loss of profit Parallel import, market risk 16

Parallel import 17

Let’s try to take the Industries’ state of mind… What are the positive and risky points? Positive publicity for the company BUT… Reputational risk Loss of profit Parallel import, market risk Emergence of resistance worldwide Intellectual property problem Lots of difficulties … 18

Source course of Pr. Jean-Pierre Osselaere 19

GILEAD SCIENCES Research-based biopharmaceutical compagny. Area of focus : - Antiretrovirals 11 marketed products such as : - Atripla (Emtricitabine+Efavirenz+Tenofovir) : 2006 - Truvada (Emtricitabine+Tenofovir) : 2004 - Viread (Tenofovir) : 2001 20

VIREAD(tenofovir disoproxil fumarate). U. S approval 2001 Immediate success. - Once-a-day dosage - Greater effectiveness - A much improved side-effect profile. Gilead planned the drug to be global in early 2003. A high priority was to make it rapidly available to millions of people in the least developed nations. 21

Gilead Access Program (April 2003) OBJECTIVE : make available the company's new drug VIREAD at no profit to developing world. 22

TIERED PRICING QUALITY GILEAD ACCESS PROGRAM PRINCIPLES PROTECTION OF INTELLECTUAL PROPERTY PARTNERSHIPS

IMPLEMENTING THE GILEAD ACCESS PROGRAM FOR HIV DRUGS IN DEVELOPING COUNTRIES 2 KEY CONSIDERATIONS PRICING DISTRIBUTION

THE ACCESS PROGRAM First approach Gilead and AXIOS (2003 -2004) 25

Price issue Affordable price for every patient. USA / EU / JAPAN High income VIREAD priced taking into account: • Therapeutic value • Innovation Price : $360 / month 68 least developed countries Widespread poverty VIREAD priced: at NO PROFIT Price: $ 39 /month ( $1. 30/day) Gilead strategy: generate sufficient volume to bring the price down Over time GILEAD lowered price to $ 17 / month. 26

Distribution issue LOCAL AUTHORITIES GILEAD SCIENCES Import waivers • LOCAL CLINICS • TREATMENT PROGRAMS Import waivers 27

After one year. . . Gilead discovered that simply offering VIREAD at low prices did not result in orders. - AXIOS never received any large order 3 main problems : - Clinics and government regulators awareness - No working experience with the drugs -The WHO medicine lists 28

THE ACCESS PROGRAM Second approach (2005 -2007) 29

GILEAD ACCESS PROGRAM EXPANSION 30

GILEAD's tiers Economic Tier Low income Lower-middle Upper-middle High income status <$ 826 $826 -$2. 999 $ 3. 000 -$ 10. 065 > $ 10. 065 Number of countries 98 (Uganda, Bangladesh, Haïti) 23 (India, Thaïland) 13 (Brazil, Malaysia, Russia) >40 (US, EU, Japan) Price of Truvada Price of Viread $ 26. 25/mo $ 17/mo About $ 45/mo About $ 30/mo Up to a 70% discount relative to high income countries $ 934. 50/mo in the U. S $ 578. 87/ mo in the U. S • : Price calculations used 2007 average wholsale prices and the recommended dosing in the drug labels; Source: Bio. Century, The Bernstein Report on Bio. Business; September 3, 2007: 15 -26 31

Managing infrastructure development IDENTIFY AND PARTNER WITH A LOCAL DISTRIBUTOR IN EVERY COUNTRY GILEAD SCIENCES ASPEN PHARMACARE ( SOUTH AFRICA) Licence to manufacture VIREAD And Sell VIREAD to clinics in Access program countries At no profit price + 5% markup for Aspen BUILD AWARENESS IN AFRICAN AND ASIAN MARKETS 32

Managing Registration of VIREAD After AXIOS management transition: VIREAD’s country by country registration - Gilead first focused on 15 countries (PEPFAR targets) Anecdotes - Gambia: immediate approval - Botswana and Zambia: rejected application - Nigeria requested more data. - South Africa returned application : too much data. - Uganda: $ 2 million shipment refused by customs! 33

• Managing corruption Gilead as a corporate policy, refused to pay bribes! As result : - Delays in registration - Generic manufacturers influence • Managing Non Government Organization Major role influencing international policy. 2 main problems : - Gilead was late to recognize WHO as a regulatory authority. - NGOs natural suspicion on the motives of pharmaceutical companies. 34

Gilead’s third approach : Non exclusive licence - Indian generic manufacters - Free pricing - 5% royalties for Gilead’s objective : - Generate competition Bring the price down over time. 35

Thank you for your attention !