Contrary to the company's claims, the FDA analysis of the adefovir studies concluded that in three studies the drug did not provide any significant anti-HIV activity, while evidence of marginal activity was seen in two other studies. The FDA, like the advisory committee, was troubled by the side effect problems, most notably kidney toxicity. In addition, the FDA analysis concluded that the company had not made a convincing case that the drug would be useful in people who had developed resistance to multiple nucleoside analogue drugs such as AZT, ddI and 3TC.
Participants in studies with adefovir will be rolled over into the existing expanded access program, but the expanded access program will otherwise not accept new requests to supply the drug. For those already receiving the drug, the program will continue for as along as the individuals and their healthcare providers feel they are benefiting from it.
Gilead officials have now concluded that they can better use their resources in developing another drug, tenofovir (PMPA), which is in the final stages of studies. Project Inform and some other AIDS advocacy groups made a similar recommendation to the company almost three years ago. Results to date suggest that tenofovir may be more potent and have fewer side effects than adefovir. Gilead will continue its development program for adefovir as a potential treatment for hepatitis B virus.
The rejection of adefovir by the FDA represents something of a milestone in AIDS research. It is the first time in recent years that the FDA has rejected a request for the approval of an AIDS drug, and it is the first time that most AIDS advocacy groups did not rally to the drug's defense. While adefovir might have been approved had it appeared on the scene in earlier years, today's environment already offers a wide spectrum of AIDS drugs, many of which are clearly more potent and less troublesome than adefovir. But whether this means that the overall standard for approval of AIDS drugs has been raised is unclear.
Back to the Project Inform Perspective April 2000 contents page.