5
damental property contributed to the
FDA approving Zenapax for preven-
tion of acute kidney transplant rejec-
tion. Protein Design Labs is currently
evaluating Zenapax in Phase I/II clini-
cal trials for MS, and it is premature to
make predictions about the Zenapax at
this time. Time will tell if Protein De-
sign Labs has found another indica-
tion for which to market Zenapax.
Corixa (NASDAQ: CRXA) is tar-
geting activated T cells differently
than the three investigational new
drugs. Corixa's lead compound is a
major histocompatibility complex, or
MHC-class II molecule, loaded with a
MS-specific peptide. Corixa's AnergiX
complex vaccine technology offers the
potential to treat several major autoim-
mune diseases, including MS by selec-
tively destroying or inactivating the T
cells involved in autoimmune disease.
In 1998, Corixa completed a randomized
placebo-controlled Phase I/II clinical
trial of AnergiX.MS complex in pa-
tients with secondary-progressive MS.
Results of this trial indicated that the
product resulted in no significant ad-
verse events, caused no generalized
immune suppression, and demo n-
strated some evidence of clinical re-
sponse. Corixa is currently seeking a
partner for AnergiX.MS complex prior
to initiating additional Phase II trials.
Although it is not yet clear,
Corixa's approach appears similar in
principle to Copaxone, which is also
thought to inactivate T cells associ-
ated with autoimmune disease. If this
is true, Corixa eventually will have to
prove that this method is superior to
Copaxone if the FDA is to consider
approving their agent.
Along these same lines, Neuro-
crine Biosciences (NASDAQ: NUBI)
is evaluating NBI-5788, an altered pep-
tide to induce a T-helper 2 response in
MS patients. This approach is similar
in principle to Copaxone and Corixa's
experimental AnergiX.MS, and will
only be approved if the agent is
proven to be more or equally effective
as Copaxone. However, at this juncture
of the therapy's development, it is far
too early to say how successful Neu-
rocrine Biosciences's drug is.
Schering (NYSE: SHR) is evalu-
ating a phosphodiesterase inhibitor,
Mesopram, as a treatment for MS. This
is a new type of agent, found to inhibit
key steps in the immune response,
leading to suppression of proinflamma-
tory subsets of lymphocytes (white
blood cells involved in the attack on
the central nervous system). The net
result is a reduction of the inflamma-
tory response.
Mesopram is administered in an
oral form. In animals, it has been
shown to prevent the onset of experi-
mental allergic encephalomyelitis
(EAE) in rats. The effect was dose de-
pendent and the clinical score of the
animal correlated well with the reduc-
tion of disease seen in the brain of
those animals. In an animal model of
relapsing-remitting EAE resembling
MS, mesopram also had a similar ef-
fect.
So far, mesopram has been tested
in normal healthy human volunteers. It
has shown that it was well tolerated at
lower doses but higher doses induced
some nausea and vomiting in a dose-
dependent fashion. With the higher
doses, nausea and vomiting were ac-
companied by cardiac arrhythmias,
which were felt to be due to vomiting.
It is obviously too early to get a syn-
opsis on Mesopram, as the drug is
being evaluated in early Phase II clini-
cal trials and there isn't sufficient data
for analysis. Nonetheless, we will
watch the development of Mesopram
and report later on clinical progress as
it comes.
Final thoughts
Unfortunately, there is no treat-
ment currently available that is capable
of preventing relapses or disease pro-
gression in MS. All of the therapies
that are currently used in an attempt to
modify the disease course have limited
efficacy and, in many cases, notable
side effects. We have mentioned sev-
eral conceivable strategies, which have
exhibited promising autoimmune in-
hibitory properties that potentially can
alter the underlying disease course. It
is unclear what strategy and agent, or
combination of agents, will ultimately
prove effective. Nonetheless, the bio-
tech and pharmaceutical industry,
along with the medical research com-
munity, must maintain focus and de-
velop new therapies to improve the
quality of life for MS patients. $$
BioTech Stock Report, March 2003
