# Presentation: 110125

## The Future of HIV Treatment 

- John C. Martin, Ph.D.
- President and Chief Executive Officer
- Gilead Sciences, Inc.

## Challenges

- New therapies are necessary to simplify treatment, decrease long term toxicities and resistance, and increase tolerability
- Late diagnosis and lack of awareness increase transmission rates and mortality/morbidity rates
- New infections are more prevalent among low income populations
- Additional challenges exist in emerging markets and least developed countries

## Development of Single Tablet Regimen

**Mar 2004   May 2004   Aug 2004  Dec 2004          Jan 2006    Apr 2006**

- U.S. DHHS announces new guidelines for expedited review of fixed-dose combinations
- BMS, Gilead, Merck announce plans to develop triple single tablet regimen

- Bioequivalence achieved

- Discussions for ex-U.S. partnerships ongoing

- Triple
- NDA
- filed

- Gilead begins formulation work for triple single tablet regimen

- Truvada
- approved

- Gilead and BMS U.S. joint venture established

- Truvada NDA filed

- FDA hosts meeting to discuss triple single tablet regimen

**Development of Single Tablet Regimen**

## How the Partnership Works

- Formulation led by Gilead scientists
- Gilead/BMS to expedite regulatory filing
- Manufacturing led by Gilead
- Combined efforts of companies’ HIV medical and sales teams to provide immediate access following approval:
- Educate physicians on product profile
- Secure formulary approvals
- Leverage best-in-class patient assistance program

## STR Addresses Treatment Challenges

- Simplifies treatment
- Simpler and more tolerable treatment regimens increase compliance by up to 30% (IJ STD & AIDS, 2003)
- In one week, an average of 17% of ARV patients missed one dose and another 17% missed two or more doses (IAPAC, 2006)
- Decreases long term toxicity and resistance profile
- Increases tolerability

## Study 934Proportion with HIV-RNA <400 c/mL (TLOVR) (n = 487)

## Study 934Adverse Events Leading to Study Drug Discontinuation Through Week 48

## Study 903: Mean (95% CI) Total Limb Fat –Years 2 through 5

**                   **

**  **

**8.0**

**8.1**

**8.1**

**Weeks**

**0**

**2**

**4**

**6**

**8**

**10**

**96**

**144**

**192                 240**

**8.2**

**0**

**4.6**

**5.0**

**5.0***

**5.5***

**d4T + 3TC + EFV**

**TDF + 3TC + EFV**

*** p < 0.001**

**Mean  Limb Fat **
**Kilograms**

## Education and Early Diagnosis are Necessary to Reduce Transmission

- Many with HIV are diagnosed late
- In the U.S., 39% of those diagnosed in 2004 received an AIDS diagnosis within a year of testing positive for HIV (KFF, 2005)
- 25% of NYC AIDS cases are diagnosed concurrent with an HIV diagnosis and these patients have a median survival of ~ 4 months (CROI, 2006)
- Need to support diverse portfolio of prevention strategies, including education
- People who know their HIV status are less likely to engage in risky behavior (JAIDS, 2005)
- Increasing routine testing initiatives will help with early diagnosis

## Early Treatment Improves Outcomes

- Early and continuous treatment with the most effective and tolerable treatments available will successfully suppress HIV
- Antiretroviral therapy coupled with prophylaxis can increase per person survival by up to 13 years (JID, 2006)
- Early, uninterrupted therapy reduces the risk of complications related to HIV (Lichtenstein, 2006)
- However, less than half of HIV infected individuals are currently on ARV therapy in the U.S. (CDC, 2005)

## Evaluating Viread as Pre-Exposure Prophylaxis

**1995****	****1996                                      2001****	**** 2003                2006**

- First human clinical data available?

- Animal data suggest Truvada has added preventive effect (CROI 2006)

- Viread approved by U.S. FDA

- Studies in monkeys demonstrate tenofovir preventive effect (Tsai)

**Evaluating Viread as Pre-Exposure Prophylaxis**

- Clinical studies of Viread as treatment begin

- CDC, NIH, UCSF, FHI, Gates Foundation and Gilead collaborate to study Viread as a preventive agent in high-risk populations on four continents;
- Protests derail two studies

## SIV Infection in MacaquesUntreated Controls

- Efficacy determined by SIV antibody titers, antigenemia, plasma and cell associated viremia and pro-viral DNA PCR.

*Science 1995*

## Tenofovir:  In Vivo Efficacy48 Hr Post-Treatment

- Efficacy determined by SIV antibody titers, antigenemia, plasma and cell associated viremia and pro-viral DNA PCR.

## Government Programs are Critical for Access

- More than half of new diagnoses were among African-Americans (CDC, 2005)
- Many patients rely on government assistance for access to treatment
- AIDS Drug Assistance Program (ADAP) provides medications to over 96,000 patients (KFF, 2006)
- Eligibility ranges from 100% to 500% of the Federal Poverty Level (FPL)
- 62% of patients are people of color
- 80% have incomes below 200% FPL
- Majority are uninsured (73%)

## Patient Assistance Provides Link to Treatment

- Gilead’s program provides same day access and reimbursement counseling
- Approximately 860 patients are receiving HIV drugs through Gilead’s Advancing Access Program (AAP)
- As of February 2006, 93% of patients on AAP transitioned to ADAP (80%) or Medicaid (13%)
- Generally, more than half of Gilead’s HIV AAP patients reside in states with ADAP waitlists

## Challenges to Access in Emerging Markets

- HIV is impacting lower income populations
- Financial resources available to treat HIV patients are limited

## Access in Emerging Markets

- Gilead has entered into a partnership with the Brazilian government, ensuring access to Viread
- Brazil’s successful National AIDS Program
- Free ARV therapy to 170,000 citizens with 20,000 expected to enter treatment this year
- Prevalence rate held at .6% since 2000
- Reduced hospitalizations by $2.2 billion over 8 years (NEJM, 2006)

## Access in Emerging Markets

- In China, 650,000 people were living with HIV in 2005 (UNAIDS, 2006)
- 20,000 patients are currently receiving treatment; need access to first-line therapy
- Gilead is in ongoing discussions with the Chinese government to make Viread and Truvada available
- Other emerging markets can make progress by prioritizing HIV/AIDS

## Global Access in Least Developed Countries

- Approximately 30 million infected HIV individuals reside in the developing world, representing 70 percent of all HIV infected people (UNAIDS, 2006)
- A total of 1.3 million patients receive ARVs in the developing world (WHO, 2006)
- Many patients eventually fail therapy and develop resistance (Yeni, 2004)

## Progress and Lessons Learned

- President’s Emergency Plan for AIDS Relief (PEPFAR)
- Provides direct assistance
- Ensures access to FDA-approved products
- Serves as the largest international donor
- Multiple industry sponsored access programs
- Gilead Global Access Program
- Provides no-profit pricing to 97 least developed countries
- On average, more than 45,000 patients receive drug through program
- Gilead is considering other models to access

## Moving Forward with New Approaches 

- Partnering with Indian generic manufacturers by offering voluntary licenses for API and tableting
- Multiple manufacturers will ensure competitive prices and the broadest access possible
- Technology transfer enables production and improves quality
- Protects IP

## The Future of HIV Treatment

- Simplified regimens will
- Provide better outcomes
- Help address access