1. Proposals for a Global Innovation System that Responds to Patients Needs and Ensures both Innovation and Access IAC –22 July 2012 The innovation & access gaps and challenges for HIV/AIDS under the Treatment 2.0 framework Mariângela Simão Rights, Gender and Community Mobilization Department UNAIDS

2. Global summary of the AIDS epidemic  2011 34.2 million [31.8 - 35.9 million] 30.7 million [28.6–32.2 million] 16.7 million [15.7–17.8 million] 3.4 million [3.1–3.9 million] 2.5 million [2.2 –2.8 million] 2.2 million [2.0 - 2.4 million] 330 000 [280 000–380 000] 1.7 million [1.6 –1.9 million] 1.5 million [1.3 –1.7 million] 230 000 [200 000–270 000] Number of people living with HIV People newly infected with HIV in 2011 AIDS deaths in 2011 Total Adults Women Children (<15 years) Total Adults Children (<15 years) Total Adults Children (<15 years)

3. People receiving antiretroviral therapy versus the 2015 target and the number of AIDS-related deaths, low- and middle- income countries, 2003–2011 AIDS-related deaths Estimated range of AIDS-related deaths People receiving antiretroviral therapy 2015 Target

4. Eligibility for antiretroviral therapy versus coverage, low- and middle-income countries, by region, 2011 The area of the larger circle represents the number of people eligible for antiretroviral therapy. The shaded circle and percentage represent coverage in 2011.

5. Prices of first-line and second-line ARV regimens for adults in low-income countries, 2008–2011 Source: Global Price Reporting Mechanism, World Health Organization, 2012. FIRST-LINE REGIMENS SECOND-LINE REGIMENS

6. The future is happening right now Migration from 1st to 2nd Line RegionAnnual Rate of Migration Africa2.6% Latin America2.6% South-East Asia1.1% Western Pacific1.1% Other Regions1.9% Countries using routine viral load monitoring 6.0% Source: Systematic review by WHO and Australian National Centre in HIV Epidemiology and Clinical Research (CROI 2010) Long term treatment programs – 25-30% patients on 2 nd line

7. Can treatment be more accessible, affordable, simple and efficient? The right drugs available at the right place and time….

8. Treatment 2.0 – a programmatic approach TREATMENT 2.0 Adapt delivery systems Mobilize communities POC and other simplified monitoring Optimize drug regimens Reduce costs Five pillars Achieve and sustain universal access & maximize the preventive benefits of ART Simplification Five pillars Achieve and sustain universal access & maximize the preventive benefits of ART Simplification

9. Reducing costs and increasing sustainability – collaboration? Role for the UN supporting countries on the use of TRIPS flexibilities, access principles – guidelines, policy papers, issues briefs Global mechanisms for IP related issues and access –Medicines Patent Pool – “ up and running” – licensing mechanisms - FDC and optimized Tx options –Ohter initiatives UNITAID, CHAI Local production and regulatory harmonization Upcoming – consultation on pricing in upper middle income countries

10. Successful country initiatives to cut the costs of ARV Note: (i) At an exchange rate of 7.40 ZAR/USD, the savings amounted to R 4.7 billion. Sources: (ii) Massive reduction in ARV prices. Johannesburg, Government of South Africa, 2010 (www.info.gov.za/speech/DynamicAction?pageid=461&sid=15423&tid=26211, accessed 15 June 2012); (iii) Mutabaazi I.I. Scaling up antiretroviral treatment using the same dollar: cost efficiency and effectiveness of TASO Uganda Pharmacy Management System of CDC-PEPFAR funded program. XIX International AIDS Conference, Washington, DC, 22–27 July 2012. Note: the content of poster discussion abstracts and poster exhibition abstracts for the XIX International AIDS Conference is embargoed until 15:00 (U.S. Eastern Standard Time) on Sunday, 22 July 2012; (iv) Viegas Neves da Silva F, Hallal R, Guimaraes A. Compulsory licence and access to medicines: economic savings of efavirenz in Brazil. XIX International AIDS Conference, Washington, DC, 22–27 July 2012. Note: the content of poster discussion abstracts and poster exhibition abstracts for the XIX International AIDS Conference is embargoed until 15:00 (U.S. Eastern Standard Time) on Sunday, 22 July2012.

11. Optimization Strategy RationaleWhat is critically needed Major challenges & risks Fixed-Dose Combinations Combining existing compatible ARV drugs in one pill or co-blister improve adherence and simplify treatment Bioequivalence studies Register results Lab-development and testing Regulatory issues Market fragmentation ARV Dose Reduction A lower dose of a given ARV drug may have the same effect on treating the disease, at lower cost /lower side effects Clinical trials (efficacy) Publish/register results Dosing guidelines Clinical trials very expensive Regulatory issues Ethical concerns Perception concerns Market confusion Reformulation (eg; extended release formulations) New formulation of an existing ARV drug can give equal level of drug in the body/blood, while taking lower dose Bioequivalence studies Register results Dosing guidelines Lab-development and testing Clinical trials less expensive Perception concerns Market confusion New Drugs & Combinations New drug with a different profile will replace a previous component in the drug regimen, with improvement of efficacy, tolerability or convenience Clinical trials (safety and efficacy)Clinical trials very expensive Market fragmentation New ART Strategies (eg: Induction- maintenance) Phased approach with a short/periodic induction using combined ARV drug regimen followed by a long term monotherapy for maintenance after stable viral suppression, with improvement of tolerability, convenience, cost and long term adherence Clinical trials (efficacy)Clinical trials very expensive Ethical concerns Perception concerns Market confusion ART Optimization

12. Addressing innovation and access to innnovation o Improving effectiveness, tolerability and resilience of 1 st line regimens o Assessing regimen switch needs: PoC VL o New drugs in the pipeline: accelerating entry into market of innovative products o Ensuring competition for innovative products: licensing mechanisms and technology transfer o Global R&D convention?

13. Pipeline for adults’ ARVs (UNITAID) Apricitabine IDX-12899 Ibalizumab Festinavir BMS-663068 Long-acting Rilpivirine Lersivirine Long-acting Dolutegravir Long-acting CMX-157 GS-7340 SPI-452 CMX-157 Therapeutic type: Attachment Inhibitor Integrase Inhibitor PK booster NNRTI NRTI PI Pre- clinical Phase I Phase IIIDiscovery Phase II Registration Market Long-acting Elvucitibine Quad EVG/COB/ TDF/FTC c. 2012 DRV/COB DRV/COB/ FTC/GS-7340 ATV/COB c. 2012 Cobicistat Jul 2011 Dolutegravir c. 2014 Elvitegravir c. 2012 Zidovudine Dose Reduction 300 mg  200 mg bid Efavirenz Dose Reduction 600 mg  400 mg bid ATV/r Dose Reduction 300/100 mg  200/100 mg bid Source: Source: Adapted from 2011 i-Base/TAG Pipeline Report (available at http://i-base.info/home/2011-pipeline-report-2nd edition-september-2011) and clinicaltrials.gov.

14. Etravirine Rilpivirine Atazanavir Dolutegravir Raltegravir Darunavir Tenofovir Maraviroc Pre- clinical Phase I Phase IIIDiscovery Phase II Registration Market Therapeutic type: Entry Inhibitor Integrase Inhibitor PK booster NNRTI NRTI PI EVG/COB Source: Source: Adapted from 2011 i-Base/TAG Pipeline Report (available at http://i-base.info/home/2011-pipeline-report-2nd edition- september-2011) and clinicaltrials.gov. Pipeline for paediatric ARVs (UNITAID)

15. What is needed to meet the challenge of scale up? o Radical simplification (Tx algorithm, drugs, services) o Innovation (in drug design, diagnostics, delivery) – shorten time between development and entry into market – registration… o Efficiency gains – service delivery o Effectiveness and impact – coverage and early diagnosis o Equity and affordability (at individual and system level) o Leadership, willingness and resources to invest

16. What do we stand for? o “No one being left behind” o Different approaches to coverage – upper middle income countries; key populations, etc o No double standards o Simpler to use, less toxic, heat stable drugs are good for patients no matter where they live o People live long and better lives o Early diagnosis. Earlier treatment initiation(?) o Better drugs and monitoring kits o …………..

17. Bridging the gap?