Could AIDS Drug Have Made a Difference?
"It might be possible for [adefovir] to work at a lower dose level, but it's not clear," Lagakos says. "It may be this was the wrong dosage of this drug to test."
Lagakos believes that the committee gave too little consideration to the findings of the large trial now published in JAMA.
"The evidence in this study was unequivocal," he says. "I was very surprised by the advisory committee's findings. I am very concerned that they made the wrong decisions, unless there is data that I haven't seen."
Gilead spokeswoman Sheryl Meredith said the firm was disappointed by the advisory committee's findings. "We were very disappointed, given the basis of our application, that they were unable to see the positive risk/benefit ratio for this drug," Meredith tells WebMD. "We were encouraged by that study that adefovir would be able to benefit patients with few other options. We had nearly 10,000 patients that had enrolled in our expanded access program. There was clearly the need for a new compound."
Accompanying the study report is an editorial by John W. Mellors, MD, chief of infectious diseases and director of the AIDS program at the University of Pittsburgh Medical Center. The editorial suggests, but does not directly state, that careful analysis of the risk/benefit ratio for adefovir might have led to different conclusions than that of the FDA panel.
"I think that [adefovir] was a marginal drug, but it might have had a niche in those who [had tried many other treatments] with no other treatment options," Mellors tells WebMD. "It gets down to the question of whether you withhold salvage therapy from people with no other options."
The Mellors editorial also made the point that the FDA panel intended to send a message to drug companies that just because a drug is urgently needed, there must be sufficient data to justify its use.
"I think the message should be out there that we have to know the safety and activity at the indicated dose," Mellors says. "Just because the situation is extreme, the standard shouldn't be lowered for approval. That's the clear message that should get out."
At the same time, Mellors does not want drug companies to become discouraged from bringing to market new drugs for HIV salvage therapy.
"It should not in any way inhibit efforts to develop drugs in experienced patients," he says. "It would be a very big shame if that was what some corporations took home."