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发表于 2002-9-10 16:38
DINNER AND DRUGS (晚餐和对话)
Disclaimer: Brett gives us something to think about regarding adefovir. We
welcome Brett's opinion. We welcome both pros and cons here at HB-L as long as everyone is polite and civil.
Steve Bingham
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[B]DINNER AND DRUGS[/B]
By Brett Grodeck
I had dinner earlier this week with two people from Gilead Sciences. We met at the Jetsons-looking restaurant in the middle of Los Angeles International Airport. My dinner companions flew in from San Francisco to talk about the drug adefovir.
Gilead's offer to speak with me was strategic but decent. Something very
unlikely from, say, a pharmaceutical empire like GlaxoSmithKline. On the
elevator to the four-story restaurant-in-a-dome, I swallowed my HIV and
hepatitis B medicines and focused my thoughts.
For months, I've been waging a jihad against Gilead for what I believed was its unethical business practices. The company makes two drugs that I care about: tenofovir and adefovir. Although chemically similar, tenofovir is
FDA-approved for HIV while adefovir is likely to be approved this month for
chronic hepatitis B virus (HBV).
The conflict stems from the fact that both drugs work equally well against
HBV. The rub is that tenofovir is safer than adefovir, which is clearly
associated with nasty side effects. Still, Gilead continues to promote the
dangerous drug versus the safer one. I came to dinner to hear why this is
happening.
POINT OF VIEW
The restaurant view spans from Malibu to Long Beach and from the ocean to downtown L.A. I had always thought the restaurant spun around, something like a spinning plate on pole. Not true, according to the hostess. But spin would still become the evening's theme.
I found the out-of-towners huddled in a booth like a football team reviewing the play book. We greeted. There was Amy Flood, Gilead's associate director of public affairs. Dressed in black and white, tall, thin, and with perfect blonde hair, Amy seemed symmetrical and measured. Next came the antiviral research honcho, Jim Rooney, M.D., who's vice president of clinical affairs, but looked more like a middle-aged surfer at home in L.A. A community-relations guy, David Nathanson, arranged the meeting.
David introduced me as an ex-AIDS activist who was too timid to speak up much in the old days of AIDS, but is now facing a mid-life crisis and a
co-infection with hepatitis B and so has latched onto the HBV thing as a
last-gasp effort to do something meaningful.
I ordered the seared ahi tuna. The restaurant theme was modern 1960s with pink-blue lighting and groovy Austin Powers decor. In the background I could hear songs from 007 films and 60s classics like The Girl from Ipanema. I wondered if rare fish is a good choice for me
BETTER LIVING THROUGH CHEMISTRY
The antiviral surfer and I immediately connected on the topics of chemicals,
viruses, livers, and immune systems. Jim oozed with interesting information -- for me, anyway.
In chemical terms, he explained why adefovir is unlikely to cause HBV
resistance. He described how most anti-viral compounds are shaped like a
pentagon. From what I could understand, different anti-virals have tiny
chemical arms hanging off the sides of the pentagon. In a way, viruses find
the dangling arms and latch onto them in order to continue replicating.
The advantage of adefovir and tenofovir is that they lack these chemical arms. When HBV encounters these drugs, it can't find an arm to grab and, thus, it can't reproduce. I tried, but I understood maybe fraction of what Jim said.
Jim seemed so passionate, so convinced that adefovir would not lead to HBV resistance, at least from a practical clinical perspective. The chemical arm argument seem reasonable. But I also know that researchers research and they usually love it. Research teams with a goal tend to look specifically for that goal. If researchers don't want to find viral resistance, chances are better
they won't.
My tuna came as a big chunk of expensive and mostly raw fish flesh. Now, one of the HIV meds I popped earlier is called Sustiva, a convenient, potent, once-daily non-nucleoside reverse transcriptase inhibitor. Early in Sustiva's development, an interesting side effect was discovered. Its makers, DuPont, initially tried to coin the side effect as "euphoria." The FDA insisted the side effect be called a "central nervous system disorder."
Call it what you will, but I was peaking at about this time. An empty stomach, adrenaline, groovy lighting, and The Girl from Ipanema heightened the effect. Soon, the music changed and I was watching a live nightclub act: a singer dressed as a Martian. From where I was sitting, the spotlight on the Martian left Jim in a shadow, a like testifier in witness protection program.
But Jim's passion persisted. As he talked about amino acids and covalent
bonding, I could imagine chemical diagrams, you know, like what Einstein would write on a chalkboard. But the diagrams seemed to emanate from Jim's head. Reminded me of the movie "A Beautiful Mind."
KIDNEY DAMAGE FOR DUMMIES
Jim described two theories on how adefovir might be involved in kidney damage. In the first theory, he said, the damage may be cumulative. That is, the damage may be related to the total amount of the drug ingested over time.
I likened the kidney to a plugged bathtub and the running shower to the damage caused from adefovir. The more the running shower filled the tub, the more damage there was to the kidney. At a certain point, the water spills over the tub and that's really bad. So, taking 120 mg of adefovir would be like turning up the shower to full blast. At 60 mg, it would take twice as long to fill the tub. And, taking 10 mg would be like a trickle: It could eventually fill tub, but it might take years.
Jim's second theory was about the natural give-and-take of damage and repair. To return to the bathtub analogy, it would be like unplugging the drain. In this hypothesis, the 10 mg trickle would never fill the tub because the water drained just as quickly. But a kidney doesn't work like a bathtub and sometimes a theory is just a theory.
The good news is that this kidney damage is predictable. A hefty body of data has shown that doctors can spot the damage before it gets serious. They do this by regularly checking phosphorus and creatinine levels while the patient is on the adefovir.
DRUG VERSUS DRUG
My slab of tiramisu arrived at the table and I asked the question: "So why has Gilead chosen not to develop tenofovir for HBV?" We all shuffled in our retro plastic chairs and the singing Martian broke into "I Will Survive." Jim took the lead and responded, "That depends on what you mean by the word 'develop'."
If 'develop' means conducting phase I, II, and III trials of tenofovir for
HBV, said Jim, then Gilead is not developing tenofovir for HBV. Nor will it.
He explained that, given the data that exists today, adefovir is safe and
effective for HBV at 10 mg and tenofovir is safe and effective for HIV. And
that's the stated direction for the company.
To be fair, Gilead has made available two separate treatments for two separate life-threatening diseases: one for HIV and one for HBV. Of course, selling an HIV drug can seem noble and be profitable, but there's less motivation to fix the problem of HBV. The medical community doesn't care much about HBV. It's too focused on Pamela Sue Anderson's hepatitis C-infected tits. And the HIV community is interested in little more than its own survival.
You'd think that the FDA would somehow get involved in drug development for chronic HBV. But in reality, it's not the traditional role of the FDA to
encourage drug development. The federal agency basically approves or doesn't approve the drugs presented to it. It also monitors the business practices of, well, food and drug companies.
In fact, the FDA has probably hindered the creation of HBV drugs by its own well-intended rules and restrictions. In the FDA's quest to protect the public from unsubstantiated claims by drug companies, it bars them from making claims that are not based on documented research. The FDA decides what drug companies can say or not say.
PASS THE BLAME, PLEASE
Back at the dinner table, Jim eagerly pointed out that Gilead -- at some
level -- is involved in clinical trials of tenofovir for HBV. He cited an
ongoing trial that's comparing tenofovir to adefovir (but only in the small
overlapping group of HIV-HBV co-infected patients such as myself -- lucky me).
So far, the results of the studies are not complete. So Gilead can't say much about tenofovir for HBV because of FDA rules. According to Gilead, the FDA is what's keeping the company tightlipped about tenofovir for HBV.
Do I believe Gilead? Mostly yes. For now, without making things complicated, I'm leaning toward Gilead's company point of view. I'm thinking about proclaiming a jihad on the FDA instead.
The end result of my e-war against Gilead and my cameos at FDA hearings on both tenofovir and adefovir was a free dinner at a wacky restaurant. But according to Amy Flood, my guerrilla tactics have also scared people with HBV more than educated them.
Leaving the Jetsons restaurant, I wondered if I had been spun into buying
Gilead's point of view. Perhaps I had. Perhaps it's the Sustiva. A good spin
job doesn't leave behind evidence. But my gut tells me that, although adefovir is not the silver bullet, it's still light years ahead of the drugs for HBV. About tenofovir's role in HBV, time and the market will tell.
Given the risk versus benefits of adefovir, would I take the drug? Yes. Does
the drug cause kidney damage? Maybe. Is it right for everyone with HBV? With the FDA's approval this month, we're all about to find out.
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