Day One-Sustiva Pricing; Remune; Agouron New NNRTI & PI

From Jules Levin

Hello from ICAAC on Thursday, September 24, 1998: Day 1 with opening session tonite at 5pm-Bruce Walker reviewing the HIV specific CD4 response discussed in the NATAP Reports May issue (click here to link to article), and Scott Hammer discussing new drugs. Before getting to them today, we had a small community meeting with Agouron at 9am to discuss-Remune HIV vaccine+HAART, and their two new drugs-a NNRTI and a PI. Following that at 2pm we had a small community meeting with DuPont to discuss pricing of Sustiva.

Sustiva has been priced at about $3900 per year, wholesale, making it about $4700/year retail. Nevirapine is priced about $2600/yr wholesale and delavirdine at $2100/yr. Dupont says the reasons for higher pricing are as follows:

• R&D- research and development. Dupont conducted an extensive program of studies on Sustiva in developing it, which they did. They conducted many studies exploring Sustiva with 2 nukes, Sustiva with indinavir and other PIs. They did, in fact, conduct more pre-approval studies than other NNRTI makers. They said at this meeting that they are committed to spending 25%+ of revenues on R&D for new AIDS drugs while the standard industry investment is 15%. They said that Sustiva costs more to make than Crixiivan but they are charging less. I asked them to provide us with hard proof that it costs that much. They also told us they have 4 new NNRTIs in development with at least one of them not being cross-resistant to Sustiva. They have said they are looking at other classes of HIV drugs and acquiring other drugs.
• They said they've spent 10 yrs researching HIV and they want to recoup expenses.
• They said they have a responsibility to their stockhlders- to show profit; stockholders could pull HIV commitment.

The community said-

• I asked for proof of their cost claims.
• An advocate from Texas requested DuPont supply drugs to all who both need it and can't get it thru ADAP. DuPont said yes.
• A portion of the community wanted to leave the meeting with a commitment to lower price. They want to cap all pricing by AIDS drug manufacturers. They say ADAP, HMOs and entire health care system can't handle high prices.
• In response some community people with HIV are concerned that HIV drug manufacturers are few-Bristol, Glaxo, Merck, Roch, Agouron, Abbott; and, with AIDS some drugs are profitable while others are not. Some are concerned that reducing profits will be a dis-incentive to developing HIV drugs. Cancer and heart disease therapy are more expensive than HIV treatment.

Commentary--I am a member of the ADAP Working Group in Washington DC. We've been lobbying for increased funding for ADAP programs. The Federal Govt has been supplying increasing funding. But, the state govts have not. I think the state govts should get bashed for not giving money to their ADAP programs. Their programs are usually overly restrictive. They have waiting lines to get into their programs. They often set unconscionable CD4, viral load, and income restrictions. The drug companies have patient assistance programs. Please email NATAP with your opinion

WHAT IS YOUR OPINION??

Please email NATAP with your opinion, so you can be a factor in the discussions. I will consider your opinion and represent them to DuPont and in other discussions. Since there are differences of opinion about how to approach issue your opinion is helpful. If you email NATAP please identify if you are a person with HIV, a doctor, etc. It will help sort out the opinions.

DuPont promised to get back to us within 30 days on costs of manufacturing, they promised to work closely with ADAP, and to help community in making sure that all who want access can get it.

Agouron Meeting

First Fred Valentine, MD of NYU/Bellevue talked about his study of Remune (an HIV vaccine) plus HAART. He reorted preliminary 20 week data of a 32 week study at Geneva. He reported improved lymphocyte proliferative responses to HIV antigens in individuals with chronic HIV-infection. These type of responses have not previously been seen in chronic infection. Bruce Walker has been able to elicit this response from individuals with acute infection. So, seeing this response in chronic infection is promising although preliminary. It's preliminary because we don't know if this effect will have a real long-term effect on the virus in humans. For example,

• Will adding Remune to HAART increase likelihood of reducing viral load to <50 copies/ml
• will viral load stay suppressed longer by adding Remune to HAART than if taking HAART alone?
• Will individuals who can't reach undetectable get to undetectable by adding Remune to HAART?
• Will the effect of Remune+HAART improve the immune response to HIV so that the immune system can better control HIV over the long-term??

We don't know the answers to these questions. New studies are starting which will address these questions. This has become a hot topic-immune based therapies as an adjunct to HAART. Valentine's study has helped to create this overall interest . As a result, the ACTG is designing studies to address this question. One study being discussed is IL-2 + rotating several vaccines including Remune + HAART. A second study was suggested by Valentine and will look at Remune + HAART over a long-term follow-up of patients to see if the immune system can improve and control HIV better due to adding Remune to HAART. In addition, Agouron is planning a study ( protocol #AG1661-705) to explore these questions. The objective of the study is to see if adding Remune to HAART increases the likelihood of reducing viral load to <50 copies/ml, and to explore additional virological and immunlogical benefits which Remune may provide. So, it is premature to say any more than this treatment approach is promising and needs further exploration. Finally, in Geneva Valentine reported that at week 16, 18/21 (86%) of individuals receiving Remune+HAART reduced viral load to <40 copies/ml, while 67% (12/18) reduced VL to <40 copies/ml with HAART alone. Valentine stressed today that this VL data was not statistically significant and should not be relied upon as accurate. Future data on VL will be more reliable.

AG-1549 and AG1776 are the NNRTI and PI. I don't have time now to review data but it is interesting and worth studying. I have to leave for Friday morning sessions.