Posted 6/10/2014 2:19 PM (GMT 0)
6.2 Immunogenicity
As with all therapeutic pr
oteins, there is potential for imm
unogenicity. In UC Trials I and II and
CD Trials I and III, in patients who received ENTYVIO, the frequency of antibodies detected in
patients was 13% at 24 weeks a
fter the last dose of study drug
(greater than five half-lives
after last dose). During treatment, 56 of
1434 (4%) of patients treated with ENTYVIO had
detectable anti-vedolizumab
antibody at any time during the 52
weeks of continuous treatment.
Nine of 56 patients were persistent
ly positive (at two or more st
udy visits) for anti-vedolizumab
antibody and 33 of 56 patients dev
eloped neutralizing antibodies
to vedolizumab. Among eight
of these nine subjects with persistently pos
itive anti-vedolizumab an
tibody and available
vedolizumab concentration data, six had und
etectable and two had reduced vedolizumab
concentrations
[see Clinical Pharmacology (12.3)]
. None of the nine subj
ects with persistently
positive anti-vedolizumab antibod
y achieved clinical remission at Weeks 6 or 52 in the
controlled trials.
The detection of antibody formation is highly dependent
on the sensitivity and specificity of the
assay. Additionally, the observed incidence of
antibody (including neutralizing antibody)
positivity in an assay may be influenced by severa
l factors, including sample handling, timing
of sample collection, concomitant medicati
ons, presence of vedolizumab, and underlying
disease. For these reasons, comparison of the
incidence of antibodies to ENTYVIO with the
incidence of antibodies to other products may be misleading.
http://general.takedapharm.com/content/file.aspx?filetypecode=ENTYVIOPI&CountryCode=US&LanguageCode=EN&cacheRandomizer=e5cee576-3ef3-4214-9962-26965f3321d9