PDL Plans Phase II / III Clinical Trial in IV Steroid-Refractory Ulcerative
Colitis
FREMONT, Calif., March 23 /PRNewswire-FirstCall/ -- Protein Design Labs,
Inc. (PDL) (Nasdaq: PDLI), today said that it has discussed with the U.S. Food
and Drug Administration (FDA) the future development pathway for PDL's
Nuvion(R) (visilizumab) humanized anti-CD3 antibody being developed for the
treatment of intravenous steroid-refractory ulcerative colitis.
Steven Benner, M.D., Senior Vice President and Chief Medical Officer, PDL,
said, "At an end-of-Phase I meeting, we explored with the agency various
potential development paths. As a result of these discussions, we are now
considering a plan to conduct two pivotal clinical trials and a retreatment
study of Nuvion in the setting of intravenous steroid-refractory ulcerative
colitis. The first pivotal study will be a Phase II / III clinical trial,
instead of a Phase III trial, and is expected to begin this year. Assuming
certain protocol-defined criteria are met at the time of the interim analysis,
the second pivotal trial would be initiated. We anticipate initiating the
retreatment study at the time of the Phase II / III study. We believe that
this approach of moving next to a Phase II / III clinical trial strikes an
appropriate balance between time of development and development risk.
"Based on this development pathway, we will not pursue a Special Protocol
Assessment; however, the proposed protocols will be reviewed in detail by the
FDA," Dr. Benner added. "Over the next weeks, we expect to more fully refine
the development plan and its impact on the overall development timeline, but
anticipate that the time to complete the proposed registrational studies will
be longer than we have previously hoped. Nuvion continues to be our highest
priority program and we are committed to making this novel therapy available
to patients with intravenous steroid-refractory ulcerative colitis. We expect
to provide a further development update by the end of May 2005."
Ongoing Phase I / II Clinical Trial in IV Steroid-Refractory Ulcerative
Colitis
PDL is currently conducting a Phase I / II clinical trial of visilizumab
in patients with IV steroid-refractory ulcerative colitis. The Phase I
portion of the trial was designed to explore four dose levels at 5, 7.5, 10 or
12.5 micrograms/kg administered intravenously on days 1 and 2 as a bolus
injection. Up to 20 patients per dose cohort will be enrolled, with up to an
additional 40 patients to be enrolled in the Phase II portion of the trial,
for an expected total of approximately 120 patients treated. PDL is now
enrolling visilizumab-naive patients in the Phase II component of the study at
the 5 micrograms/kg dose level, administered on days 1 and 2.
In a completed, 32-patient Phase I study of two dose cohorts that was
reported in May 2004, a strong signal of activity was observed in the first
dose cohort given at 15 micrograms/kg on days 1 and 2, in which all eight
patients achieved remission. A continued strong signal of activity
subsequently was observed in the second dose cohort given at 10 micrograms/kg
administered on days 1 and 2. At the 10 micrograms/kg dose level, 19 of 24
patients responded to treatment and of these, 13 achieved remission.
"Visilizumab has demonstrated activity at all dose levels tested to date," Dr.
Benner commented.
In each of the studies reported to date, the most common adverse events
have been associated with the cytokine release syndrome, which generally
consists of flu-like symptoms typically characterized by fatigue, nausea,
chills and headache and a transient rise in liver enzymes. The flu-like
symptoms were generally transient in nature, were seen less frequently
following the second day of treatment and typically resolved within 24 hours
following the second treatment. In addition, visilizumab induces a transient
decline in T cells and frequently an associated transient rise in Epstein-Barr
virus (EBV) titers. The decline in T cells could result in an increased
incidence of infections, although this has not been observed thus far in the
clinical trials in patients with IV steroid-refractory ulcerative colitis.
PDL currently expects to present additional clinical information regarding
visilizumab at the Digestive Disease Week meeting to be held in Chicago,
May 14-19.
In September 2004, PDL announced that the FDA had granted Fast Track
status to the investigation of visilizumab in patients with IV
steroid-refractory ulcerative colitis. Designation as a Fast Track product
indicates that the FDA will facilitate the development and expedite the review
of a new drug that is intended to treat a serious or life-threatening
condition, and that demonstrates the potential to address an unmet medical
need. However, Fast Track designation does not mean that the FDA will
expedite approval of any application for the product or guarantee approval of
the product.
About Visilizumab
Visilizumab is a humanized non-FcR binding monoclonal antibody directed at
the CD3 antigen on T cells. Increasing evidence implicates T lymphocytes as
the primary immune cells mediating the induction and progression of
inflammatory bowel disease. While the mechanism of action of visilizumab in
ulcerative colitis is still being characterized in ongoing studies, early
research has demonstrated that visilizumab induces selective apoptosis of
activated, but not resting human T cells in in vitro cell biology experiments.
If these observations are established in vivo, it may provide an explanation
to the rapid therapeutic benefit in ulcerative colitis. Research studies
continue on visilizumab's effects on the resting T cell populations that
appear not susceptible to in vitro apoptosis.
About PDL
Protein Design Labs is a leader in the development of humanized antibodies
to prevent or treat various disease conditions. PDL currently has antibodies
under development for autoimmune and inflammatory conditions, asthma and
cancer. PDL holds fundamental patents for its antibody humanization
technology. Further information on PDL is available at http://www.pdl.com.
The foregoing contains forward-looking statements involving risks and
uncertainties and PDL's actual results may differ materially from those in the
forward-looking statements. Factors that may cause such differences are
discussed in PDL's Annual Report on Form 10-K for the year ended
December 31, 2004, and in other filings made with the Securities and Exchange
Commission. In particular, there can be no assurance that Nuvion will prove
safe and efficacious in clinical studies for the treatment of ulcerative
colitis, or that PDL will undertake a Phase II / III or Phase III clinical
studies of Nuvion for the potential treatment of steroid-refractory ulcerative
colitis, or that the FDA will ultimately accept the Company's development
program as approvable or that such program will ultimately lead to regulatory
approval.
NOTE: Protein Design Labs, the PDL logo and Nuvion are registered U.S.
trademarks of Protein Design Labs, Inc.
SOURCE Protein Design Labs, Inc.
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Related links:
http://www.pdl.com
CONTACT:
James R. Goff, Senior Director, Corporate
Communications of PDL, +1-510-574-1421, or jgoff@pdl.com
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