Atripla Approved: First One-Pill, Once-Daily Complete Antiretroviral Regimen

By Liz Highleyman

On July 12, the Food and Drug Administration (FDA) approved Atripla, the first-ever complete one-pill, once-daily HAART regimen. Atripla is a fixed-dose tablet containing:

Gilead Science's nucleotide reverse transcriptase inhibitor, tenofovir disoproxil fumarate (Viread), 300 mg;
Gilead's nucleoside reverse transcriptase inhibitor, emtricitabine (Emtriva), 200 mg;
Bristol-Myers Squibb's non-nucleoside reverse transcriptase inhibitor, efavirenz (Sustiva), 600 mg (marketed by Merck and Company outside the U.S.).

Expedited Approval

The Atripla coformulation was approved in less than three months under the FDA's "fast track" expedited review process.

"The availability of Atripla marks the culmination of 10 years of efforts to simplify dosing while helping to achieve and maintain effective viral suppression for adults infected with HIV-1," said John Bartlett, MD, of Johns Hopkins University.

Gilead's Study 934, reported in the January 19, 2006 issue of the New England Journal of Medicine, showed that Truvada was more effective than Combivir (AZT/3TC) when used in combination with efavirenz (80% vs 70%, respectively, with undetectable HIV viral load), and that it was better tolerated and led to fewer treatment discontinuations. Data presented at the 7th Workshop on Clinical Pharmacology of HIV Therapy this past April showed that the Atripla coformulation is bioequivalent to the three separate drugs used together.

Atripla is the product of the first cooperative effort by two pharmaceutical companies in the HIV/AIDS field to combine their patented drugs into a single product. After two failed attempts, the companies discovered a bi-layer technology that produced adequate blood levels of all three drugs.

It is also the first multiclass antiretroviral coformulation available in the United States. Several generic fixed-dose combinations are approved for use in developing countries, though none are once-daily. Atripla also will be available for use in the 15 countries covered by the President's Emergency Plan for AIDS Relief (PEPFAR).

"This is a monumental accomplishment," said Frank Oldham, Jr., Executive Director of the National Association of People with AIDS (NAPWA). "On behalf of the one million Americans living with AIDS, we are grateful to our partners in the scientific community for their research and development of Atripla."

Cost, Availability, and Cautions

Atripla is expected to cost $1,150 per month, about the same as Truvada and efavirenz purchased separately. However, patients may save money because insurance companies are likely to consider it a single drug, requiring one co-payment. The companies said the new combination pill would be available within 1-2 weeks.

Atripla may be used as a stand-alone regimen or in combination with other antiretrovirals.

Cautions regarding Atripla are the same as for its component agents:

lactic acidosis associated with NRTIs;
kidney impairment and possible bone loss associated with tenofovir;
central nervous system side effects related to efavirenz;
potential for birth defects due to efavirenz.

Both tenofovir and emtricitabine are active against the hepatitis B virus (HBV), but are not approved for this indication; discontinuation of Atripla may cause liver inflammation "flares" in people coinfected with HIV and HBV.

Complete prescribing information is available at www.atripla.com.

For more information about the development of Atripla, see the recent New York Times article, "New Medicine for AIDS Is One Pill, Once a Day."

7/14/06

Sources
Food and Drug Administration. "FDA Approves the First Once-a-Day Three-Drug Combination Tablet for Treatment of HIV-1." Press release. July 12, 2006.

Bristol-Myers Squibb and Gilead Sciences. "U.S. Food and Drug Administration (FDA) Approves ATRIPLA (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg), the First Once-Daily Single Tablet Regimen for Adults with HIV-1 Infection." Press release.