FDA approves two combination pills, Epzicom and Truvada; comment on commercial race to once-a-day nucleosides.

On August 2, 2004, the U.S. FDA approved once-daily combination antiretroviral pills from two companies: GlaxoSmithKline's Epzicom (Ziagen [abacavir] + Epivir [3TC]), and Gilead Sciences' Truvada ([Viread [tenofovir] + Emtriva [FTC]). Both are taken once a day, combined with other antiretrovirals NOT part of the nucleoside/nucleotide class. Truvada was given accelerated approval (which means that Gilead must complete additional work) because approval was based in part on clinical trials of Viread with 3TC--a drug similar to FTC but not the same. Epzicom received final approval on August 2.

Since both ingredients of each combination were previously approved in the U.S., these new approvals reduce the pill count, but do not create new medical options for patients. They may ease financial burdens for some, because there is only one "prescription" instead of two, reducing some co-pays--and helping to meet some health plans' arbitrary limits on the number of prescriptions a patient can have at any one time.

Glaxo will provide a limited number of waivers to physicians, allowing patients to obtain true Epzicom in order to give their health plans time to include it in coverage. We do not have details of this program.

An FDA press release on these approvals is at http://www.fda.gov/bbs/topics/news/2004/NEW01099.html

Because Epzicom contains Ziagen, all the precautions about drug hypersensitivity reactions to Ziagen must be followed. This reaction may be more common with once-daily dosing; a study in 770 patients found more cases of severe hypersensitivity in the group that took all the medicine once per day, instead of taking it in divided doses twice per day (5% of the once-daily Ziagen group had severe hypersensitivity, vs. 2% of the twice-daily group--see Epzicom and Ziagen prescribing information for doctors. Epzicom is dosed for once-daily use only. If hypersensitivity occurs, Epzicom (or any other form of Ziagen) must be stopped and NEVER restarted. Glaxo has prepared material to help patients recognize when this reaction might be occurring, so that they can talk with their doctor immediately about how to proceed.

Comment: Concern on the New Once-Daily Nucleosides

AIDS Treatment News is concerned that commercial competition could drive a rush to once-a-day regimens that include the nucleoside/nucleotide class of drugs, without enough attention to what is best for each patient. Some issues need more thought before there is a mass switch for the convenience of once a day.

One problem is the hypersensitivity danger with abacavir, mentioned above. The traditional twice-daily nucleoside drugs do not cause this reaction.

Also, two three-drug regimens that doctors agree should never be used as the only antiretroviral treatment are tenofovir plus 3TC plus abacavir, or tenofovir plus 3TC plus ddl; these were unexpectedly found to cause serious drug resistance in many cases, including the K65R and MI84V/I mutations. The problem was seen in regimens without AZT, which doctors have noticed helps to prevent this kind of resistance. We are concerned that the newly approved combinations are too close to comfort to a part of the failed 3-drug regimens, and are intended to be used only without AZT.

The new combinations may well be successful, and some patients will benefit. But we are not convinced that all the questions have been answered well enough to justify a wholesale switch, just because once a day is spun as the thing to do, in direct-to-consumer advertising. The FDA approved both combinations on the same day--which is "fair," but could lead to a horse race between the two companies' products that may not be in the public interest.