"I was diagnosed with AIDS wasting," says Sharp. Wasting is a late-stage AIDS malady, a sign that the body has started to consume its own muscles in a misguided effort to stay alive. It is almost always fatal. Yet Sharp's diagnosis occurred more than two years ago. Now, thanks to a controversial AIDS drug, Sharp says he is back in shape.
"I was eating again. I had an appetite again, which I didn't have before. I was sleeping well. I had boundless energy," he says. "I even went back to ballet class and did a performance. I used to be a ballet dancer. All in all, I regained my life."
Sharp says he was saved from the perils of AIDS wasting by the so-called human growth hormone. It is not a new drug. More than a decade ago, South San Francisco's Genentech won Food and Drug Administration (FDA) approval to manufacture human growth hormone for treating short-statured young children. In fact, human growth hormone was the first bioengineered hormone ever brought to market, and it marked a brave first step for the then-nascent biotech industry.
But despite the concerted efforts of San Francisco AIDS activists, human growth hormone has remained mostly beyond the reach of those suffering from AIDS wasting. The drug costs $150 a day -- or about $54,000 a year. And Serono, the drug company that has proposed marketing the hormone as a treatment for AIDS, has been unable to win FDA approval to bring the drug to market for that purpose. Its most recent attempt, in March, resulted in a rare FDA split vote, as an advisory committee ruled 8-7 against Serono, saying the company had not proved that the hormone was both safe and effective as an AIDS treatment.
Now, however, the FDA is on the brink of granting accelerated approval for the hormone.
"I think we are very close. We're coming down to the wire now," says Gina Cella, director of community relations for Serono. "We've had many discussions with the FDA. We've provided them with new, additional data."
For its part, Serono has apparently agreed to exchange full approval, which it initially wanted, for accelerated approval, which comes with some strings attached. That's essentially what the AIDS activist community has been pushing for: access to the drug while tests continue, rather than waiting until all the results are in, a process that has already stretched on for eight years.
"Just very recently, like within the last day, Serono has agreed to apply for and to accept accelerated approval if it's offered," says Ron Baker, director of treatment education at the San Francisco AIDS Foundation, and who testified on behalf of the drug's approval before the FDA in March. "That will grant approval to a drug more quickly than under normal circumstances, but it comes along with some restrictions."
"Really we want to give this drug the best opportunity for approval," Cella says.
"We've been hearing rumors that any day now they're going to be reaching approval," says Sharp, a member of ACT UP Golden Gate and director of Healing Alternatives, the largest AIDS resource library in the nation. "We've come a long way, and it's a big victory for ACT UP Golden Gate and for a lot of people."
The road toward FDA approval for the hormone as an AIDS wasting treatment has been rocky indeed. AIDS wasting is a specific, late-stage syndrome marked by the body's erroneous decision to consume proteins instead of fats for energy. The body thus strips itself of muscle and cannot process food properly, resulting in starvation and the marked loss of weight. Reversing AIDS wasting means more than just gaining weight -- the body must begin to process nutrition properly again, and actually add lean body mass, or muscle.
In 1992, Genentech conducted trials of the hormone as an AIDS wasting treatment and then abandoned the idea of using human growth hormone as an AIDS drug. The Genentech trials were Phase I and Phase II tests, which are both relatively preliminary levels of the FDA-required process to bring a drug to market. The final pre-market test of a drug is called a Phase III trial, and successful results in that phase are required for FDA approval. Genentech's tests didn't get that far.
"We found no evidence of efficacy," Genentech Corporate Communications Officer Kathleen Rinehart says.
That's the void Serono entered. Serono, which is the Massachusetts-based U.S. subsidiary of Swiss drug company Ares-Serono, manufactures and distributes the hormone in 60 countries worldwide. But in trying to comply with the FDA requirements, Serono fell short, proving conclusively in one crucial trial only that people gained weight, rather than that the weight they gained was measurable lean body mass.
"It was supposed to confirm the drug safety, and they looked at weight gain, but they did not look at lean body mass," says the AIDS Foundation's Baker. "This was an inexcusable oversight on the part of Serono, not to have measured lean body mass in this Phase III trial."
The FDA ruled that those trials were insufficient. AIDS activists, though, argued that the hormone had been used safely in children for more than a decade -- and that FDA approval before Serono had finished conducting more tests would be appropriate.
"We felt that while we were disappointed that the data presented were not better and that Serono had not done as great a job as might be wished, we had to balance that against what we felt was the need for the community for this therapy, which we feel is promising," Baker says.
At stake in the FDA approval for the drug is more than just access to it. Under current law, any doctor can prescribe human growth hormone -- Genentech's, Eli Lilly's, or any other company's approved product -- for any use, on a case-by-case basis, according to FDA Public Affairs Specialist Janet McDonald. That is to say, even though the FDA has only approved the hormone for growth deficiencies in children and adults, doctors are free to use their judgment to prescribe it for other maladies where they think it might be effective. But unless the FDA approves the specific use of the drug, then public and private insurance companies will most likely not pay for it.
If, on the other hand, the FDA does approve human growth hormone as an AIDS treatment, then Medicaid will automatically add the drug to its list, says Medi-Cal spokesman Ken August.
"Under federal law any drug that is specifically for AIDS or cancer is automatically added to the medical formulary," August explains. "Boom -- it goes on and it's medically approved."
In addition, if the drug does gain FDA approval, then other publicly funded AIDS drug programs, such as the state-and-federally-funded AIDS Drug Assistance Program (ADAP), will be expected to provide it, activists say. And with the cost of the hormone as high as it is, that has led some to speculate that the reason for the FDA's balking is more budgetary than scientific.
When human growth hormone was first introduced, it was not genetically engineered but instead came from the pituitary glands of human cadavers. That made the hormone very rare and expensive -- and, as it turned out, dangerous. The early natural versions of the hormone resulted in the infection of three people with Creutzfeldt-Jakob disease, the human equivalent of bovine spongiform encephalopathy, or mad cow disease.
The Genentech hormone posed no such danger, as it was bioengineered. That hormone, rather than being taken from corpses, was made in vats with E. coli bacteria, rather like the process of fermenting beer. Much easier, some observers argued, than pillaging the brains of corpses, and yet the price of the hormone remained high. Genentech won a specialty patent for its human growth hormone, which gave it exclusive marketing rights for seven years. Complaints about the price of the hormone, along with other so-called "orphan" drugs, so named because they were developed to address diseases that affected fewer than 200,000 people in the U.S., prompted a review of the exclusivity laws. But no changes were made.
Right now, Serono's hormone is available to some 1,300 people nationwide through an expanded-access drug program, a federal program that allows experimental drugs to be provided to people with AIDS. Historically, these drugs have been provided free of charge. But Serono has asked for, and received, permission to charge for participation in the drug access program, the first time that that has ever happened. Public and private insurance programs, as well as individuals who can afford it, have been charged the approximately $54,000 a year for the hormone. But just last week, AIDS activists say they negotiated a cap on the amount of money Serono would charge for the drug, bringing the price down to $36,000 a year.
That's still outrageously high, AIDS activists say. "Their view of something like growth hormone is clearly to charge all the market will bear," says Stephen Le Blanc, of ACT UP Golden Gate. "That has got to stop."
"Two years ago you didn't hear AIDS activists talking too much about price," he says. "This year every activist both in America and really across the world is talking about price and trying to convince drug companies to change their marketing strategy."
That will be one of the focuses in Vancouver, where the XI International AIDS Conference convenes July 7. There, activists promise to be focusing on both AIDS wasting and on drug company prices. Instead of selling the drug at high cost to a few, Le Blanc argues, why not sell it to many at a lower price?
"I think all of these companies are going to hear this message very loudly," Le Blanc says.
But, Cella says, Serono hasn't decided what price it will charge if the hormone does win FDA approval. If the approval, in fact, does occur.
"It could be a couple of weeks," Cella says. "It could be a month.