developed by Pfizer, was approved for treatment-experienced
patients in August 2007 based on data from the MOTIVATE
trials showing that it worked well in patients with
HIV that was resistant to older classes of antiretroviral
uses one of 2 co-receptors -- CCR5 or CXCR4 -- along with
the CD4 receptor to enter host cells. Only patients with
HIV that exclusively uses CCR5 (determined by a tropism
test) are eligible to use maraviroc. People with recent
infection are more likely to have only CCR5-tropic virus,
suggesting maraviroc may be well-suited for this population.
some experts have expressed concerns about the efficacy
of maraviroc for first-line therapy. In the Phase
3 MERIT trial, treatment-naive patients with high viral
load were less likely than those taking efavirenz
(Sustiva) to achieve viral suppression < 50 copies/mL.
analysis (known as MERIT ES) using a more sensitive viral
tropism assay found that some of the patients initially
classified as having exclusively CCR5-tropic HIV actually
had dual or mixed-tropic virus. When these patients were
excluded (since they should not have used the drug in the
first place), maraviroc and efavirenz worked equally well.
caused fewer side effects than efavirenz overall, especially
neuropsychiatric symptoms such as insomnia, and had a favorable
lipid profile. Data from the FDA released prior to last
week's meeting revealed no new or unexpected safety concerns.
As a newer drug, however, the possibility remains that unexpected
toxicities could show up with longer-term use.
have also shown that maraviroc increases
CD4 cell counts more than other antiretroviral classes
and seems to plays a role in reducing inflammation, which
may confer benefits beyond viral load suppression.
the other hand, maraviroc is less convenient, since it must
be taken twice daily. It addition, it requires the expensive
Trofile tropism test, which discourages some providers from
using it. A recent study, however, suggests that a lower
tropism test may work equally well in classifying likely
FDA panel -- which included agency officials, independent
researchers and clinicians, pharmaceutical company representatives,
and patient advocates -- ultimately decided that while there
are other highly effective antiretroviral drugs available,
it is an advantage to have a wider selection of medications
to choose from when tailoring individual regimens. "We're
not looking for the absolute best, we're looking for an
option," said committee member Victoria Cargill, MD,
from the National Institutes of Health Office of AIDS Research.
is pleased that the Committee has recognized the effectiveness
and safety profile of maraviroc in patients who are starting
HIV therapy," said Pfizer executive director Howard
Mayer in a press release issued by the company. "Today's
discussion marks an important step in expanding available
treatment options for patients with HIV infection and we
look forward to working with the FDA to further address
the points raised by the panel."
panel members asked Pfizer to collect more data, including
from studies of pregnant women and patients with tuberculosis
or hepatitis B or C coinfection.
full FDA is not required to accept its advisory panels'
recommendations, but it typically does so.
National Prevention Information Network. US FDA Panel Backs
Wider Use of Pfizer HIV Drug. October 9, 2009.
Inc. FDA Advisory Committee Recommends Approval of Pfizer's
Selzentry for Use in Patients Starting HIV Therapy for the
First Time. Press release. October 8, 2009.
Levin. FDA antiviral advisory committee testimony excerpts.
October 8-9, 2009.