Once-a-day combination pill approved for HIV.
The Food and Drug Administration on July 12 announced the approval of Atripla, a fixed-dose combination of three antiretroviral drugs: efavirenz (Sustiva), emtricitabine (Emtriva), and tenofovir disoproxil fumarate (Viread). Sustiva is a nonnucleoside reverse transcriptase inhibitor and Emtriva and Viread are nucleoside reverse transcriptase inhibitors. The three drugs together are one of the most widely used first-line therapies for treatment-naive patients who have no viral resistance to the three components.
The FDA approved Atripla for use alone or in combination with other antiretroviral products for treating HIV-1 infection in adults, making this the first pill that can be taken once a day for treating HIV/AIDS. Another triple antiretroviral drug combination is available, but it must be taken twice a day, often with other antiretroviral drugs.
During a press conference in which the approval was announced, Dr. Jeffrey Murray, deputy director of the FDA's division of antiviral products, said he expects that the niche for Atripla will be as a standalone regimen for patients with HIV who are starting treatment, because the combination is one of the first-line preferred regimens for initiating therapy.
Patients on a different first-line regimen who want to reduce their pill burden or who are not tolerating their regimen could also switch to Atripla, as long as they do not have virus that is resistant to any of the drug's components, said Dr. Murray, who is also a practicing physician who treats patients with HIV.
"This is a huge breakthrough in terms of being able to have one pill once a day without food requirements," Dr. Donna Sweet of the University of Kansas, Wichita, said in an interview. "The caveat is it works well as long as you take it religiously and you don't already have some resistance," added Dr. Sweet, who has a large HIV practice. Some data suggest as many as 10%-11% of patients will already have some viral resistance when infected, so "one has to be very diligent in assessing resistance" before the regimen is started, she noted.
Atripla was approved in 3 months under an expedited review. The development of the combination pill is a result of what the FDA is calling an unprecedented collaboration between Bristol-Myers Squibb, the manufacturer of Sustiva, and Gilead, which manufacturers Emtriva and Viread. Emtriva and Viread are also available in a fixed-dose combination marketed by Gilead as Truvada. Sustiva was approved in 1998, Viread in 2001, and Emtriva in 2003. Truvada was approved in 2004.
Atripla will be marketed jointly in the United States by BMS and Gilead.
The combination of the three components of Atripla was evaluated in 244 HIV-1 infected patients; after 48 weeks of treatment, 80% had a marked reduction in HIV and a substantial increase in CD4 counts, according to the FDA. Atripla will be available in the United States within a week of the approval at a cost approximately equal to the cost of the individual components, according to the manufacturers.
Dr. Sweet, a speaker for BMS and Gilead as well as other manufacturers of antiretroviral drugs, said that one of the potential benefits of the triple drug combination pill is a reduction in prescription copayments, because patients will not have separate copayments for each of the three drugs. Still, some plans have charged higher copayments for other combination antiretroviral drugs.
During the press conference, Dr. Andrew C. von Eschenbach, the FDA's acting commissioner, called the approval a landmark in HIV/AIDS treatment, pointing out that a decade ago patients on combination HIV therapy would typically take 12-15 pills throughout the day and sometimes in the middle of the night. The combination pill is a particularly important advantage in developing countries, where a simplified drug regimen "will make access and compliance far more effective."
Dr. Murray Lumpkin, the FDA's deputy commissioner for international and special programs, said that the FDA is "extremely hopeful" that the fixed-dose combination pill will be particularly helpful for the HIV-infected population in the developing world. "The fact that people can take one pill once a day will not only meet the medical needs of patients but the logistical needs, and in developing countries that has been one of the highest hurdles in trying to win the war on HIV/AIDS."
The Atripla label includes a black box warning about lactic acidosis that can occur with the drug and a warning that discontinuing treatment in people with hepatitis B can result in severe flares of hepatitis B. Other serious adverse events associated with the three drugs include serious hepatotoxicity, renal impairment, and severe depression.
The most common side effects with the combination treatment include headache, dizziness, abdominal pain, nausea, vomiting, and rash.
BY ELIZABETH MECHCATIE