FDA Approves Gilead's Stribild Pill for
HIV
Posted: 08/27/2012
August 27, 2012 —
The US Food and Drug Administration (FDA) today approved Gilead Sciences Inc's Stribild
pill for patients with untreated HIV infection.
The approval
follows a 13–1
endorsement of the drug by an FDA advisory committee back in May.
Formerly called
"Quad," Stribild is a combination of the investigational integrase
inhibitor elvitegravir and boosting agent cobicistat with Truvada, which
consists of Gilead's nucleotide reverse transcriptase inhibitors emtricitabine
(Emtriva) and tenofovir (Viread). It is the first once-daily single-tablet
regimen containing an HIV integrase inhibitor.
"Exciting"
Development
"This
approval is an important and exciting development. Taking 1 pill once a day has
a great charm to patients," John G. Bartlett, MD, chief of the Division of
Infectious Diseases and professor of medicine at Johns Hopkins University
Medical Center in Baltimore, Maryland, said in an interview with Medscape
Medical News. Dr. Bartlett is a member of the Medscape HIV/AIDS editorial
advisory board.
"This is the
first new front-line drug we've had in a fairly long period of time," Dr.
Bartlett noted, "and it's different in the sense that it not only has a
new integrase inhibitor but it also has a new boosting agent cobicistat instead
of ritonavir, which has been used in the past."
As previously
reported by Medscape Medical News, in 2 large double-blind
randomized phase 3 trials published in the Lancet in June, Stribild was
as effective and as safe as 2 other recommended HIV drug regimens among
treatment-naive adults. The other regimens were
efavirenz/emtricitabine/tenofovir and a ritonavir-boosted regimen of
atazanavir/efavirenz/tenofovir.
In recommending
approval of Stribild, members of the FDA advisory panel said the drug has a
generally acceptable safety profile, but there should be effective monitoring
for potential kidney problems among patients taking it. In clinical trials,
patients taking Stribild were more likely to experience adverse renal
events.
Tenofovir, a
component of Stribild, has been associated with new or worsening kidney
problems in some patients. "Cobicistat is also a little bit tricky because
it changes lab readings on kidney function in a way that doctors are going to
have to learn to understand," Dr. Bartlett commented. Overall, Stribild
has "a lot of advantages, but a disadvantage, of course, is that it's
brand new," he added.
As with some other
HIV drugs, Stribild's label will carry a boxed warning concerning the
possibility of severe liver problems and lactic acid build-up in the blood,
both of which can be fatal. According to an FDA news release, "The Boxed
Warning also states that Stribild is not approved to treat chronic hepatitis B
virus infection."
Switch to
Stribild?
Although Stribild
is approved for treatment-naive patients, some patients receiving an existing
regimen may want to switch to Stribild, Dr. Bartlett noted, and that is a
decision that should be made on a case-by-case basis.
"A lot of
patients who are already in a regimen that they like probably won't change
their regimen," he told Medscape Medical News.
"Most of us
tell our patients that unless there is a reason to change and you've achieved
success by getting no detectable virus, it's probably better to just continue
with the regimen. If there is a problem due to a side effect, resistance, or
convenience or pill burden, then this drug becomes a candidate," Dr.
Bartlett said.
What will Stribild
cost? "We don't know right now, but I believe it will be competitively
priced — it's going to have to be in order to compete," Dr. Bartlett said
A New 4-Drug, Single-Pill Option for HIV
Paul
E. Sax, MD
Posted:
08/27/2012
Hello,
this is Dr. Paul Sax from Brigham and Women's Hospital and Harvard Medical
School. Today I'd like to discuss the recent US Food and Drug Administration
(FDA) approval of the coformulated tenofovir, emtricitabine (FTC),
elvitegravir, and cobicistat pill -- the so-called Quad.
It
was approved by the FDA for use in treatment-naive patients with HIV, and its
approval was based on the results of 2 phase 3 clinical trials. The trials were
double-blind, placebo-controlled trials: one compared Quad with
tenofovir/FTC/efavirenz[1] and the other compared Quad with
tenofovir/FTC/ritonavir-boosted atazanavir.[2] In both trials, Quad
was clearly noninferior, which was the primary endpoint, and, notably, it was
numerically superior, although not statistically superior.
There
were some differences in toxicity, in particular between Quad and the
tenofovir/FTC/efavirenz regimen.[1] Quad had fewer central nervous
system side effects and fewer rash side effects, but it had a bit more nausea.
Overall treatment discontinuations were rare between the 2 arms. Quad was very
similar to the boosted atazanavir regimen's side-effect profile.[2]
One
thing that's important to note is that Quad contains cobicistat. Cobicistat is
a pharmacokinetic enhancer that is known to inhibit secretion of creatinine in
the renal tubules. This leads to about a 0.1- to 0.2-mg/dL increase in serum
creatinine, and this increase leads to a decrease in the estimated glomerular
filtration rate (GFR).
However,
it has been shown that this is not an actual decrease in the GFR, so as long as
the elevation is on the relatively modest side, then one can continue the
tenofovir/FTC/elvitegravir/cobicistat.
In
these studies, it was also shown that patients who developed actual tenofovir
toxicity, a tubulopathy, had an increase of 0.4 mg/dL or greater, so we could
use that as sort of a benchmark in clinical practice to decide whether a
patient is having this benign elevation from cobicistat or a potentially more
serious toxicity from tenofovir.
In
summary, we now have 3 single-pill options for the treatment of HIV infection:
tenofovir/FTC/efavirenz; tenofovir/FTC/rilpivirine; and now
tenofovir/FTC/elvitegravir/cobicistat.
Patients
and providers typically like these single-pill options. They tend to improve
compliance and probably reduce medication errors. But the real question, of
course, will be a pharmacoeconomic one: In the context of having a lot of
potentially less expensive options that are generic, will the benefits of these
single-pill options outweigh the costs?
Overall,
it's good news for our patients and providers and another option for HIV
treatment: tenofovir/FTC/elvitegravir/cobicistat.
Thank
you very much.
References
- Sax PE, DeJesus E, Mills A, et al. Co-formulated
elvitegravir, cobicistat, emtricitabine, and tenofovir versus
co-formulated efavirenz, emtricitabine, and tenofovir for initial
treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial,
analysis of results after 48 weeks. Lancet. 2012;379:2439-2448. Abstract - DeJesus E, Rockstroh JK, Henry K, et al. Co-formulated
elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate
versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and
tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a
randomised, double-blind, phase 3, non-inferiority trial. Lancet.
2012;379:2429-2438. Abstract
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