Tenofovir: FDA Hearing on Important New AntiretroviralOctober 19, 2001 A note from TheBody.com: The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information! The FDA's one-day public hearing on tenofovir (brand name VireadTM), a new antiretroviral being developed by Gilead Sciences, took place October 3 near Washington D.C. (see AIDS Treatment News # 370, August 24, 2001). This meeting of the Antiviral Drugs Advisory Committee (a group of outside experts convened by the FDA) also included consultants selected for this particular meeting because of their special expertise.
Everyone who spoke agreed that tenofovir should be approved; the FDA had no issue with approval, which is expected shortly. In clinical trials the drug has shown a 0.6 log decrease sustained for the length of the trial (up to a year so far), when added to an antiretroviral regimen which was failing to suppress the virus -- a difficult test for a drug, and probably not the way tenofovir will generally be used. (Usually at least some of the other drugs in the regimen would be changed, often after resistance testing -- although it is too early to know for sure how tenofovir will be used in practice.) Resistance to tenofovir seems slow to develop, although resistant viruses do occur. The drug is easy to use (it is taken only once a day, with food), and so far has shown excellent safety in human tests, with side effects comparable to those reported by volunteers who received the placebo. One major issue at the hearing was whether the FDA should recommend tenofovir for combination use in HIV treatment for any patient -- including those starting antiretrovirals for the first time -- or only recommend it for advanced patients, where there is currently more data. All activists who spoke wanted the general indication, but for a variety of reasons the committee tended toward the more restrictive one (there was no formal vote). Activists want to free doctors and patients from possible reimbursement hassles if they decide to use the drug in front-line therapy; they also wanted to make sure the company was not punished for testing tenofovir first in advanced patients, which activists and the FDA have urged companies to do, since these patients most need new options. But committee members were concerned that less is known about first-line use and more will be known next year, when the indication could be changed. Some felt that the lack of complete information about first-regimen use changed the risk/benefit ratio of using a new combination vs. a standard one. Others noted that ADAPs (the AIDS Drug Assistance Programs, run separately by each state) are unlikely to micromanage patients, so they will not deny reimbursement if a physician uses the drug outside of the indications formally approved by the FDA. Some saw the drug's indication as mainly a marketing issue. (Doctors are free to prescribe an approved drug for any patient, without being bound by the indications.) Long-Term Safety IssuesHuman safety data were very good -- in particular, there was none of the kidney toxicity that had been seen in adefovir when studied for HIV at doses of 60 and 120 mg daily. (Adefovir, a much less effective antiretroviral in the same drug class as tenofovir, is no longer being developed for HIV, but is a promising potential treatment for hepatitis B, in much smaller doses.)But animal studies using tenofovir doses much higher than those given to people had found a bone problem, osteomalacia -- a lack of normal mineralization of the bone (this disease is called rickets in children, osteomalacia in adults). While the danger appears to be low -- the condition can be treated, and reversed completely in animals when the drug was stopped -- two bone experts brought by the FDA as consultants to the committee thought that certain steps should be taken now in order to head off possible problems in the future:
We left the hearing with the impression that this issue should not delay approval of tenofovir -- the drug is needed now, and the bone risks are not immediate if they exist at all. But the discussion pointed out the need for biochemical research on the mechanism of the bone changes in animals, and strongly suggested at least some baseline testing when the drug is started, for correction of relevant nutritional deficiencies if necessary. (According to Gilead, much of this work had already been done but was not presented at the hearing because the FDA was already comfortable with the data. And bone markers are now being measured in study 903, a clinical trial of tenofovir in treatment-naive patients.) Other PossibilitiesTenofovir may have other important uses than the HIV treatment for which it will be approved:
For More InformationA summary and a transcript will be on the FDA Web site, at: http://www.fda.gov/ohrms/dockets/ac/acmenu.htm (click on '2001', then 'Anti-Viral Drugs Advisory Committee').Usually the transcript is available 30 days after the meeting, the summary approximately 90 days after. Some other information about the October 3 meeting is already on this site. Copyright 2001 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.
A note from TheBody.com: The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information! ![]()
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