ANNUAL REPORT 2012 - TiGenix

elated fistulas were administered Infliximab
at induction at weeks 0, 2 and 6. Patients who
had ongoing fistula response to the drug at
week 14 were re-randomized and placed on
a maintenance regimen administered every
8 weeks thereafter. By the end of the trial,
36 % of the patients that went on to receive
a maintenance therapy continued to be in
complete remission. If remission after initial
induction is taken into account, efficacy of
Infliximab at 1 year is limited to 23 % (only 48 %
of patients evaluated after induction therapy
achieved a complete remission). Remission
is hereby defined as complete healing. This
is thus in large contrast with the results of
TiGenix’s Phase II study using Cx601, in which
56 % of treated fistula tracts healed (complete
closure and re-epithalization of external
opening) after 24 weeks.
Humira maintenance trial (“CHARM”).
Efficacy results were 33 % rate of complete
closure at 56 weeks.
- Cimzia (certolizumab) - UCB : Although not
developed for the treatment of fistulizing
Crohn directly, fistula healing was a
secondary endpoint in one of Cimzia’s
maintenance trials (PRECISE 1) and a small
number of patients in PRECISE 2 also had
fistula as a baseline. In none of the two
trials did Cimzia outperform efficacy of
placebo. The EMA refused the Marketing
Authorisation for Cimzia to treat active
Crohn’s disease. Nevertheless, Cimzia
received FDA approval for treating adults
with moderate to severe Crohn’s disease
who have not responded to conventional
therapies.
Other biologics being used in the treatment
of luminal Crohn (but not specifically
approved for the treatment of fistulizing
Crohn) are :
- Humira (adalimumab) - Abbott : Second
generation anti TNF, which has been
approved for the treatment of Crohn’s
disease (but not fistulizing Crohn’s).
Humira has the advantages of requiring
only subcutaneous dosing (instead of
intravenous infusion) and being a fully
human antibody. Fistula healing was
studied as a secondary endpoint in the
- Tysabri (natalizumab) – Elan-Biogen :
Approved by the FDA (not by the EMA)
for the treatment of moderate to severe
Crohn’s disease. However, Tysabri is not
effective in the treatment of fistulizing
Crohn’s disease and the ENACT-1, ENACT-2
and ENCORE trials all specifically excluded
patients with active fistulas.
- An interesting note is that not all
TNF- -neutralizing medication is effective
in treatment of Crohn’s disease as Enbrel
(etanercept) has proven to be worse than a
placebo in Crohn’s disease.
70 TiGenix I annual report 2012