| Volume 10 Issue 3 | April 2003 |
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| C o n t e n t s | |||||||||||||||||||||||||
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| #1 | Rapacious Returns | ||||||||||||||||||||||||
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| #2 | Full Count SIre of Twin Failures Hivid and Invirase, Roche Tempts Fate with High Profile T-20 Launch |
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| 'ADAP body blow'
On Thursday March 13th the U.S. FDA granted approval to T-20 (Fuzeon), the first of a new class of antiretroviral drugs that block HIV from infecting cells. Immediately after the news of Fuzeon's approval, Roche officials said they would not disclose Fuzeon's U.S. price until closer to the drug's launch date. Then the company announced on Thursday (3/20) that T-20 would be priced at just shy of $20,000 for a year's supply. This is more than double the next most expensive AIDS drug. Excerpts from a March 7th joint statement by AIDS organizations and individuals, prepared by TAG's Rob Camp and San Francisco's Matt Sharp, appear below. Text of the complete position paper is posted at TAG's web site. Research and advocacy have brought forth 16 approved antiviral medications targeting two different stages in the HIV life cycle. These drugs, when used in potent combinations, have significantly reduced morbidity and mortality in people living with HIV. However, for the large number of people who have been treated for years and have developed drug-resistant viral strains, the present drugs are often insufficient to achieve durable viral control. Because HIV rapidly evolves resistance and cross-resistance to available drugs, there is a clear need for therapies that target other points in the HIV life cycle. T-20 is the first drug of a new class of HIV inhibitors that perform entry inhibition. More specifically, T-20 is one of a subset of entry blockers called fusion inhibitors. It acts by preventing the envelope of HIV from fusing to its target's cellular membrane. For treatment experienced individuals with multiple-drug resistant virus, adding a drug from a new inhibitor class in combination with drugs from previously used classes is thought to be the most effective strategy for achieving durable viral suppression. As with all other HIV therapies, T-20 must be used in a combination, preferably with other new agents, in order to have the biggest punch. T-20 has been shown to be active in vitro against virus using either CXCR4 or CXCR5 co-receptors, or both. Its mechanism of action occurs outside of the cell wall, and the drug does not appear to penetrate cells to any significant extent. Therefore T-20 is not expected to disrupt intracellular metabolic pathways or stimulate intracellular destruction. Initially developed by Trimeris, Inc., since 1999, F. Hoffmann-La Roche and Trimeris (Roche/Trimeris, the sponsor) have collaborated on the development and production of commercial quantities of T-20. Both companies will market the drug within the U.S. and Canada, and Roche will solely market the drug in the rest of the world. It is high time that a new HIV drug class becomes available. Based on positive results from two large phase III pivotal studies, Roche/Trimeris submitted an application to the Federal Food and Drug Administration (FDA) for final approval and the FDA granted priority review status. Although therapeutically promising, T-20 is unfortunately not an easy drug to use and may be difficult for some to access. Its drawbacks include:
Twice daily injection A specific program is needed to deal with the complexity of drug reconstitution and self-injection. Patient experience may be very helpful in elucidating some basic "dos and don'ts." Fuzeon has challenges in common with other injectable drugs, including the significant concerns many former injection drug users in recovery have regarding any use of needles as a potential trigger for relapse. Problematic Injection Site Reactions (PISRs) Because both the cause and the resolution of these may be key to success on this drug, we will be using the term "PISR" (problematic injection site reactions) in this paper, not the sponsor term "ISR." Roche/Trimeris needs to learn more about why these PISRs occur and must look into other delivery mechanisms for the compound. Besides PISRs, T-20 has side effects (grade 3 and up, in fewer than 10% of people) of nausea and vomiting, neutropenia, anemia, and elevated SGPT and amylase. Reconstitution Supply According to the sponsor, the commercial manufacture of T-20 is the first time that synthetic peptides have been produced at this scale. Once the companies believed they had a worthwhile product, they scaled up production by designing a new, specialized production plant in Colorado. However, difficulties in developing production capacity and acquiring raw materials have limited drug supply and have held back implementing the expanded access program. Until the new plant came on-line, small-scale production had only been able to meet the needs of clinical trials and a small expanded access program (1,200 slots world-wide that took an excessive six months to enroll). When the expanded access program was being planned, activists demanded that it enlist people equitably and from as many diverse populations as possible. The community was assured that new and different investigators would be chosen by the company to ensure that the drug was offered to people who typically were left out of such access programs, and to ensure that those needing a salvage therapy would receive T-20. Unfortunately, as with most expanded access programs to date, the sponsor delivered "too little, too late." The program has only recently begun providing significant amounts of drug even as final FDA approval is days away. This timing has allowed little access to the drug outside of clinical trials. T-20 has been studied primarily in a pre-treated population, in adults who are multi-therapy experienced, with multi-resistance and limited treatment options. This population; i.e., those most in need, must be guaranteed continued first access to this drug, regardless of the ultimate label indication approved by the FDA. Full-scale production for marketing had been promised to be up and running without hitches by the beginning of 2003. But after reports that only half the amount hoped for would be available at time of launch, a limited initial distribution plan has been developed. Producing enough T-20 for all the research, the expanded access program and expected market demand has been a major stumbling block in the development of this drug. Because of the production difficulties, and the fact that a drug of this complexity has never been produced before, there is no promise that enough drug can be produced in a timely manner to reliably supply all who need it. The sponsor is reserving a 5 month supply for every patient who begins therapy with T-20. This plan is heartening, although it may be contributing to the astronomical price. With only a 16% success rate for bringing viral load < 50 copies/mL in the heavily pre-treated trial participants, and with drug supply limited, this drug may need to be rationed to those most in need - those without other treatment options. Use in other populations has not been studied, and the risk-benefit ratio in a treatment-naive population has yet to be determined. Finally, it should be noted that there are no study results demonstrating the impact of T-20 on the clinical progression of HIV disease. Price Read the entire position paper, "Fuzeon: Breaking Barriers or Breaking the Bank?" at the TAG website: www.treatmentactiongroup.org. |
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| #3 | Tipping Point As MSF, Oxfam Redefined the Possible, Y2K Activist Trek to Durban Marks A Watershed |
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'Small piece of history' The buzz before Durban was all about security. The crime would be terrible. No one would be able to step outside their hotel rooms without being macheted to pieces. Also, there were no hotels rooms within 5,000 miles of the conference center. And, the conference would be terribly organized with little planning or coordination. The pharmaceutical industry, supposedly concerned about the security of their employees, drastically cut the number of attendees. Government did the same. Most shamelessly, many of the researchers stayed home. They complained that the conference would not be safe and would not have any important science anyway, so why bother. This from people who would normally fly ten hours a week to make a fifteen minute presentation where all they do is read from their slides. Yes, the crime in South Africa is a problem, but the white flight (or non-flight) was pretty shocking. Is it possible that the security concern was a cover? Is it too cynical to think that many people involved in drug development and clinical research just did not want to attend a conference where their work was not all that important—since there were no means (or will) to deliver their miracle drugs to the over 5 million people infected with HIV in the host country? Where the latest research data on drug resistance or lipodystrophy is not terribly relevant? Where the exhibitionism of industry marketing is not only useless, but rubs salt in an ever-enlarging wound? And yet Durban was a milestone conference, and anyone and everyone who attended left with a profound sense that they had witnessed a small piece of history and went home determined to make a difference in the lives of tens of millions of Africans. Indeed, most of the researchers who did attend the conference spoke of how incredibly moved they were by the experience. Some of them, like Charlie van der Horst, actually left jobs of many years to take on research and health care provision in Africa. David Barr carries us into the twenty-first century with the penultimate installment of his history of the international AIDS conference. While many people came to Durban feeling that treatment access was just not a possibility in Africa, despite the urgent need; they left feeling that treatment access was possible and had to be pursued. Yes it would be difficult. But it was no longer a question of can it be done; but rather, how can it be done. Tony Fauci was incredibly moved by Edwin Cameron's opening speech, calling it the best speech he'd ever heard. I should admit at the outset that I came to Durban skeptical. Not about whether treatment access was just and necessary, but conflicted about whether or not it really was possible to do. I worried that Western activists were pushing an agenda based on their experience and not based on the experience, needs and capabilities of the people and countries there. I still worry about that, but I no longer question whether treatment access is and should be a high priority. I now believe that unless we—and here I mean all of us—commit to making treatment access a high priority in any and every response to HIV, then all efforts to address HIV will fail. I do not see how a prevention program can succeed without providing the promise and hope of treatment to those who are infected. How can a prevention program succeed if overwhelming death and illness surround it? How can you expect people to value life if their governments and medical establishments do not? I arrived in Durban and checked into the Holiday Inn. I had a room overlooking the ocean and could watch the surfers in the annual night surfing competition from my window. The conference center was a few blocks away and was gleaming and new. Despite the concerns about poor organization, the conference was flawless. The center was comfortable, easy to navigate, and the sessions were well planned. It was the most diverse group of attendees ever and people were excited to be there. The opening day was the high point for me. The day began with forum organized by Médecins Sans Frontières and the Treatment Action Campaign (TAC), the South African AIDS activist group. The meeting was packed with hundreds of people, mostly black South Africans. We heard reports on the need for and attempts to provide treatment access. The high point was Justice Edwin Cameron, who gave us a preview of his opening plenary speech. A white South African with AIDS, Justice Cameron spoke of his illness and his recovery since starting antiviral drugs. He talked about the injustice of his good fortune compared with the sickness and death facing most of his countrymen and women because of their inability to obtain treatment. It is not possible to write about this speech and do it justice. It needs to be seen. Get the tape. After the meeting, there was a large rally outside the City Hall, organized by TAC. Union leaders, church leaders, activists, and even Winnie Mandela addressed the crowd. Thousands of people were wearing T-shirts that had "HIV POSITIVE" in large letters on the front. This alone was a chilling piece of activism as we were only 30 miles from where a woman was stoned to death for publicly declaring her HIV status. After the rally, we marched through the streets of Durban, yelling for treatment access. People were singing songs and dancing in the streets in a scene that was so reminiscent of all the anti-apartheid demonstrations I had seen on television. It was thrilling to be surrounded by South Africans demanding access to treatment and demanding that their government and all the governments of the world address the AIDS crisis in Africa and worldwide. The march was peaceful, but very exhilarating. There was one scary moment. At some point, a guy driving a car got stuck in the march. He could not move forward or backward. Had he been patient and waited, he could have easily left the scene. No one was interested in him or was trying to keep him there. But instead of being patient, he started honking and then yelling at the marchers to get out of the way. When they did not listen, he began driving a bit faster, threatening to run down the marchers in front of him. Then the demonstrators did pay attention to him. They surrounded the car, telling him to stop. This only made him more agitated. He started yelling. He sped up again. The demonstrators surrounded his car, trying to stop him. My boyfriend Sam was one of those. The guy then pulled out a gun and pointed it right at Sam. Others intervened, and I think some police finally showed up. The guy turned the corner, and the crisis was quickly over. But it was scary for a moment. We marched to the soccer stadium, where the conference opening ceremonies would take place. The soccer stadium was packed. Finally the show began. (And that is what it was.) Broadcast nationwide, the opening ceremonies were complete with musical numbers, hundreds of fake Zulu drummers (some were white) descending from the air on wires, dancing girls, you name it. It was a huge Las Vegas-style production, and it didn't have much to do with AIDS. After the extravaganza and a few introductory speeches, the South African President, Thabo Mbeke, came out for his speech. Here was a perfect moment for the President to shame the pharmaceutical industry and the western/northern governments into committing the resources needed to address the worst AIDS epidemic on the planet. Instead, he let them off the hook. Much of what he said was true: that AIDS is a disease born and spread by poverty, and that the many conference attendees speaking about how South Africa should or should not respond to its AIDS crisis had little knowledge or understanding of the country and would leave in a week not having seen how people really live. But rather than say what should be done, he stopped there. He did not discuss treatment. He did not lay out a prevention strategy. He basically said to leave him alone. People were furious and started leaving the stadium in droves. Also, we were hungry and it was time for us to have dinner and complain about the President. Most of us missed the boy with AIDS who spoke after the President, myself included. My friends and I went back to the Holiday Inn for a big Japanese dinner—a meal that cost more than most people make in a month in South Africa. This contradiction was continual and ever-present: I was a tourist, a tourist who cares, but a tourist nonetheless. But after the conference was over, I would leave with my friends for a vacation of a lifetime, touring the game parks and visiting Capetown. I am unbelievably lucky to have been born when and where I was [well okay, until George 43]. There I was in South Africa, being inspired by the treatment activists, arguing with people about what to do and how do it. But my role in the both the crisis there and how to address it was increasingly confusing to me. I was surrounded by activists from the U.S. who were rapidly abandoning their AIDS agenda at home to concentrate on an epidemic in a country very foreign to them. I became suspicious—not of their motives, but of their missionary zeal. It is too easy for us Americans to impose our ideas and solutions on others. I found myself making assumptions about everything without wanting or trying to. I knew that there was work I could do that would help, but I did not want to make assumptions about what that should be. Instead, I wanted to be guided by the activists there. They should determine how we in the U.S. should assist them. In the years since, they have shown that, while they appreciate our assistance, they do just fine on their own. I decided that when I went home I would raise money for TAC. That seemed like something they would need—and I could do. Gregg Bordowitz made a videotape based on TAC's work during the conference. Sam Avrett and I mailed it out along with a letter also signed by Gregg Gonsalves, Peter Staley and Mark Harrington. The letter and tape made the rounds and we ended up raising over $75,000 for TAC. I arrived home from South Africa and my phone was ringing as I opened the door. It was Gregg Gonsalves, who had arrived home a few minutes before me. Stephen Gendin was dead. He had been diagnosed with lymphoma just before the conference started and had to cancel his trip. I had met his former boyfriend, Mark Aurigemma, in the airport on the way over and he told me that news. The chemo was very hard on Stephen and apparently caused a heart attack. Everyone was away when it happened, except Hush. The memorial two weeks later was packed. Mark Aurigemma, Hush, Moisés Agosto and others spoke beautifully about Stephen. Larry Kramer talked of forming terrorist cells and new Irgun tactics. ¤ |
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| #4 | TAG at Ten: The Year 2001 | ||||||||||||||||||||||||
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| email: tagnyc@msn.com 611 Broadway, Ste. 612 · New York, NY 10012 phone: (212) 253-7922 · fax: (212) 253-7923 copyright © 2003 TAG |
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