Enfuvirtide
May Increase Pneumonia Risk
SUMMARY
The FDA recently approved changes to the package label
for enfuvirtide (T-20; Fuzeon) warning of a possible increased
risk of bacterial pneumonia. |
During
Phase 3 clinical trials, researchers observed a higher rate
of bacterial pneumonia in patients assigned to receive the
fusion inhibitor enfuvirtide compared with those not using
this drug.
The
U.S. Food and Drug Administration (FDA) therefore asked Roche
to conduct further post-marketing studies of this possible
side effect. The latest label change is based on data from
an observational study again showing an increased pneumonia
risk among enfuvirtide recipients.
"Based
on this observational study, it is not possible to exclude
an increased risk of pneumonia in patients treated with Fuzeon
compared to non-Fuzeon treated patients," reads the updated
label. "It is unclear if the increased incidence of pneumonia
is related to Fuzeon use. However, because of these findings,
patients with HIV-1 infection should be carefully monitored
for signs and symptoms of pneumonia..."
Below
is a recent announcement from the FDA describing the label
changes.
Update
to Fuzeon (enfuvirtide) Label Regarding
Incidence of Bacterial Pneumonia
April
29, 2011 -- Updates to the Warnings and Precautions, Pneumonia
subsection of the Fuzeon (enfuvirtide) package insert were
approved on April 28, 2011 in response to results of a study
conducted under a Postmarketing Commitment. Drug sponsor,
Roche, submitted the results from an "Observational Cohort
Study on the Incidence of Pneumonia in HIV-1 Patients Treated
with Fuzeon." The study was conducted as a result of
findings during the initial review of the registrational Phase
3 trials, which showed a relative increase in the incidence
of bacterial pneumonia for subjects receiving Fuzeon versus
control subjects. The increased pneumonia findings were included
in the Warnings and Precautions section of the package insert.
The findings from the study are included in Warnings and Precautions
section 5.3 Pneumonia of the package insert as follows. The
new text appears below in italics.
5.3 Pneumonia
An increased rate of bacterial pneumonia was observed in subjects
treated with Fuzeon in the Phase 3 clinical trials compared
to the control arm. The incidence of pneumonia was 2.7% or
3.2 events/100 patient-years in subjects receiving Fuzeon
+ background regimen. On analysis of all diagnoses of pneumonia
(pneumonia, bacterial pneumonia, bronchopneumonia, and related
terms) in T20-301 and T20-302, an increased rate of bacterial
pneumonia was observed in subjects treated with Fuzeon compared
to the control arm (6.9%, 6.7 pneumonia events per 100-patient-years
versus 0.6 events per 100 patient-years, respectively). Approximately
half of the study subjects with pneumonia required hospitalization.
Three subject deaths in the Fuzeon arm were attributed to
pneumonia; all three had serious concomitant AIDS-related
illnesses that contributed to their deaths. Risk factors for
pneumonia included low initial CD4 lymphocyte count, high
initial viral load, intravenous drug use, smoking, and a prior
history of lung disease.
Because it was unclear whether the higher incidence rate
of pneumonia was related to Fuzeon use, an observational study
in 1850 HIV-infected patients (740 Fuzeon treated patients
and 1110 non-Fuzeon treated patients) was conducted to evaluate
the risk of pneumonia in patients treated with Fuzeon. A total
of 123 patients had a confirmed or probable pneumonia event
in this study (62 in the Fuzeon treatment arm with 1962 patient-years
of observation and 61 in the non-Fuzeon treatment arm with
3378 patient-years of observation). The incidence of pneumonia
was 3.2 events/100 patient-years in the Fuzeon treatment arm
and 1.8 events/100 patient-years in the non-Fuzeon treatment
arm. The hazard ratio, adjusting for other baseline risk factors,
was 1.34 (95% C.I. = 0.90-2.00). Based on this observational
study, it is not possible to exclude an increased risk of
pneumonia in patients treated with Fuzeon compared to non-Fuzeon
treated patients.
It is unclear if the increased incidence of pneumonia is related
to Fuzeon use. However, because of these findings, patients
with HIV-1 infection should be carefully monitored for signs
and symptoms of pneumonia, especially if they have underlying
conditions which may predispose them to pneumonia. Risk factors
for pneumonia included low initial CD4 cell count, high initial
viral load, intravenous drug use, smoking, and a prior history
of lung disease.
The complete revised label will be posted soon at Drugs@FDA.
5/3/11
Source
R
Klein and K Struble, FDA. Update to Fuzeon (enfuvirtide) Label
Regarding Incidence of Bacterial Pneumonia. HIV/AIDS Update.
April 29, 2011.
