Gilead Plans Clinical Trial of 4-in-1 Antiretroviral Combination Pill Containing Experimental Integrase Inhibitor Elvitegravir

By Liz Highleyman

The development of combination pills containing 2 or more antiretroviral drugs has reduced the "pill burden" and improved the convenience of HIV treatment.

Currently, there are several coformulations combining 2 or 3 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), as well as Gilead Sciences' Atripla (tenofovir/emtricitabine/efavirenz), which offers a complete 3-drug regimen in a single once-daily pill.

As reported last week by the Bloomberg financial news service, Gilead is now planning studies of a new all-in-one "quad" antiretroviral pill containing the NRTIs tenofovir and emtricitabine (the same ones in Atripla and Truvada) plus the company's experimental integrase inhibitor elvitegravir and a boosting agent, making it the first-ever 4-drug antiretroviral coformulation.

The first and only approved integrase inhibitor -- Merck's raltegravir (Isentress) -- is approved for treatment-experienced patients, though it has demonstrated promising results in treatment-naive individuals. Elvitegravir is currently in Phase 3 studies in treatment-experienced patients.

Like most current protease inhibitors (PIs) -- but unlike raltegravir -- elvitegravir works better when "boosted" with a small dose of another drug that slows its processing and increases its concentration in the body. The PI ritonavir (Norvir) is usually used for this purpose, but Gilead is testing its own boosting agent, GS9350, for use with elvitegravir. Thus, all 4 drugs in the quad pill are owned by Gilead, whereas the efavirenz component of Atripla is patented by Bristol-Myers Squibb. Gilead hopes to make the new pill once-daily, like Atripla (while raltegravir is taken twice-daily).

An advantage of the quad pill over Atripla is that in studies to date, elvitegravir appears to have few adverse side effects, and does not cause the neuropsychiatric side effects (such as dizziness and unusual dreams) attributable to efavirenz. In addition, animal studies so far suggest elvitegravir does not carry a birth defect risk like efavirenz, though it has not been studied in pregnant women.

According to the Bloomberg story, Gilead expects to begin the first clinical trial of the quad pill in the second half of 2009. Company president John Milligan said Gilead is discussing the size and scope of the trial with the U.S. Food and Drug Administration (FDA).

"The fixed dose quad pill is the most exciting thing we're working on," he told a Bloomberg reporter during the annual JP Morgan Healthcare Conference last week in San Francisco.

1/20/09

Source
M Chase. Gilead to Start Advanced Trial of First Four-in-One AIDS Drug. Bloomberg News. January 12, 2008