AIDS Vaccine R&D (post-AIDSVAX®)

• R&D challenges

• Products in development

• Funding AIDS vaccine R&D

• Access and advocacy

Today, deaths to AIDS account for more than half of all deaths in 7 African countries

AIDS deaths as a percentage of total deaths, 2001Source: US Census Bureau

50% 100%

Even in the US, HIV transmission is on the rebound where once it showed significant signs of slowing

32% of gay black men ages 15-22 are HIV-infected

Even in the US, HIV transmission is on the rebound where once it showed significant signs of slowing

32% of gay black men ages 15-22 are HIV-infected

To end this epidemic, treatment, behavioral

intervention, and prevention technologies must all be pursued aggressively.

Why is developing an AIDS vaccine so difficult?

• Traditional vaccine approaches too risky(live attenuated, whole killed)

• Huge variability of HIV genetic structure (role of subtypes?)

• Ideal immune response still unknown• Antibodies?• Cellular immune responses?• Others?

• No ideal animal model

• Significant clinical trial challenges

Non-Scientific Challenges

• Impact of partially effective vaccine unknown • Difficulty in testing combinations of vaccines• Ethical challenges in conducting trials

• Treatment for infected participants• Prevention counseling• Access

• Manufacturing challenges• World still does not value vaccines • Limited investment in AIDS vaccines by govt, companies

But an AIDS vaccine is increasingly likely

• New knowledge that high levels of antibodies can protect • Evidence that cellular immune responses protect humans

• Exposed but uninfected sex workers• Long term non-progressors

• Better ways to measure immune responses (Cellular,

mucosal antibodies)• Some vaccines now protect monkeys against SIV disease• Phase III trials can be done - AIDSVAX

The AIDSVAX® Trials

North America trial • 5000 MSMs, 400 high risk women• 2/3 vaccinated, 1/3 placebo • clade B/B• Seven doses: at 0, 1, 6, 12, 18, 24, 30 month

Thai trial • 2500 IDUs• ½ vaccinated, ½ placebo• clade B/E • Seven doses: at 0, 1, 6, 12, 18, 24, 30 months

AIDSVAX: Not Effective in preventing HIV infection in this Phase III trial

Placebo group Vaccine group Efficacy(95% confidence)

All volunteers1679 volunteers 98 infections (5.8%)

3330 volunteers 191 infections (5.7%)

3.8%(-22.9%–24.7%)

White, Hispanic1508 81 (5.4%)

3003 179 (6.0%)

-9.7%(-42.8%–15.7%)

Black, Asian, other 171 17 (9.9%)

327 12 (3.7%)

66.8%(30.2%–84.2%)*

Black 111 9 (8.1%)

203 4 (2.0%)

78.3%(29.0%–93.3%)**

Asian 20 2 (10.0%)

53 2 (3.8%)

68.0%(-129.4%–95.5%)

Other 40 6 (15.0%)

71 6 (8.5%)

46.2%(-67.8%–82.8%)

* p < .01 ** p < .02

Source: VaxGen Inc.

Volunteers in AIDSVAX Trial Did Not Increase Their Risk Behavior

Have HIV+ partner

Unprotected anal sex

Unprotected anal receptive sex

Vaccine groupPlacebo group

50%

40%

30%

20%

10%

0

Men

who h

ave s

ex w

ith m

en in

gro

up

0 6 12 18 24 30 36

Month into trialSource: VaxGen Inc.

Some Key Challenges in AIDS Vaccine R&D

• Too many “Me Too” products

• Most products now in development not expected to prevent

disease

• Difficulty in testing best combinations

• Clinical trial infrastructure

• Private sector investment still very limited

• Funding, funding, funding

Overview of Clinical PipelineALVAC+ gp120 Aventis/VaxGen (Phase III approved)

DNA + Adeno Merck (Phase I-II)

Adeno +ALVAC Merck/Aventis (pre-clinical)

DNA + Adeno (A,B,C) NIH VRC (Phase I soon)

DNA + MVA, AAV IAVI Partners (Phase I-II)

DNA + MVA Emory University, NIAID

Tat-nef , env + adjuvant Glaxo-SmithKline (Phase I-II)

VEE AlphaVax (Phase I soon)

VSV + DNA, IL-12, IL-15 Wyeth (Phase I soon)

Gp140, DNA, SFV Chiron (Phase I soon)

Lipopeptides ANRS (Phase I)

Therapeutic HIV Vaccines

• Now have vaccines that generate more potent cellular immune responses

• Hope is that vaccines with HAART can “teach” the immune system to control HIV without drugs

• Merck, Glaxo SmithKline now testing HIV vaccines as therapies in HIV-infected individuals

Vaccines are undervalued as a healthcare product

Total worldwide revenues for all vaccines (pediatric, adult)

$6.5 billion per year

Total revenues for biggest selling single drugs Approximately $7 billion

Total revenues for Viagra® Approximately $1.8 billion

Still not a priority:What the world spends on developing

AIDS vaccines

1996: $ 175 million(the cost of producing ONE major Hollywood movie)

2001: $ 400 million (the cost of producing TWO major Hollywood movies)

IAVI AIDS Vaccine R&D Spending Project

Analysis of public sector spending by area • NIH - $329m 2002, IAVI - $31m 2002, ANRS – $10m

Comprehensive analysis of private sector investment

• Huge differences in current estimates

Development of generic cost assumptions• Pre-clinical, Clinical, Phase III, Manufacturing, Staffing, Lab assays

Estimate of total global investment/spending

AIDS Vaccine R&D:Future Funding Challenges

• Flat NIH Funding• Competition among PPPs for global health R&D funding• Weakening global economy• Pressure on pharmaceutical companies (patent expiration,

pricing)• Uncertain biotech market • Disappointing VaxGen results

Standard Vaccine Access Timeline

Years afterstart ofpre-clinicalresearch

5 10 15 20 25 30 35

12-15 years

Vaccinelicensed

in 1country

17-23 years

Vaccinelicensedin most

countries

Country-by-countryapprovals

Manufacturing scale-upFinancing for developing countriesDelivery systems 35+ years

2/3deployment

in developingcountries

Access Challenges: Setting Priorities

• Demand Estimates • Manufacturing• Regulatory• Financing• Delivery

AIDS Vaccine Advocacy Coalition

• AVAC Annual Report: How Do You Fight a Disease of Mass Destruction and Other Questions on the Road to an AIDS Vaccine?

• Background reports on AIDSVAX results

• Legislative collaboration with IAVI, microbicide groups, MVI

June 1981…CDC reports 5 young men……

Since then ...

79,000,000infections

10 new HIV infections a minute 95% of new infections in developing countries