4
BioTech Stock Report, March 2003
and Betaseron are packaged as lyophi-
lized (freeze-dried) powders and re-
quire mixing with a diluent to reconsti-
tute as a liquid for injection. However,
a diluent syringe will be introduced by
Chiron in the U.S. and Japan in the
second half of this year. Biogen has
submitted a supplemental regulatory
filing for a prefilled liquid formulation
for Avonex in the U.S. and Europe and
expects approval in the second or third
quarter of this year. Both products'
improvement will increase ease of use.
We anticipate that Biogen's share
of the MS market would increase, as
the FDA recently approved Avonex
for the treatment of early-stage MS.
This decision makes Avonex the first
drug to treat early-stage MS in the U.S.
In our opinion, this will provide a mar-
keting advantage for Biogen in the U.
S. over Chiron (Betaseron), Serono
(Rebif) and Teva (Copaxone), but
eventually the competition will proba-
bly follow Biogen's lead.
Biogen was asked by the FDA to
notify doctors that in a small number
of cases, MS patients taking Avonex
developed pancytopenia and thromb o-
cytopenia. These blood-related condi-
tions are not life threatening and inci-
dences are rare. We don't believe this
new information will negatively impact
sales of Avonex.
When patients enter secondary-
progressive MS or have the progres-
sive-relapsing form of the disease few
treatments are available. One drug ap-
proved for this phase of MS is Novan-
trone, which is now marketed by Am-
gen (NASDAQ: AMGN). Novan-
trone's mechanism of action targets
proliferating lymphocytes in the in-
flammatory lesions.
In the event MS patients do ex-
hibit relapses while being treated with
Avonex, Betaseron, Rebif or
Copaxone, the patient's clinician will
probably prescribe a corticosteriod.
Corticosteroids are commonly used in
MS for the management of acute exa c-
erbations because they have the ca-
pacity to close the damaged blood-
brain barrier and reduce inflammation
in the CNS, thereby minimizing any
permanent damage resulting from the
attack. Although methylprednisolone
is among the most commonly used
corticosteroids in MS, it is only one of
several possibilities. Other commonly
used corticosteroids include dexameth-
azone, prednisone, betamethasone,
and prednisolone.
New treatment options in the
pipeline
Despite the results with current
MS therapies more effective therapies
are still needed to provide MS patients
with a better quality of life. To this
end, several biotech and pharmaceuti-
cal companies are testing new agents
to better serve this patient population.
The remainder of this article will focus
on these new therapies.
Biogen, in association with Elan
(NYSE: ELN), is developing one of the
most promising new therapies in clini-
cal development for MS. Antegren,
which is in late Phase III clinical trials
is a humanized monoclonal antibody
that targets the alpha-4 integrin mole-
cule found on activated T cells. The
molecule works by blocking the entry
of activated T cells into the lesion,
thereby reducing the presence of cells
that contribute to the inflammation and
damage. We are encouraged by the
clinical results collected to date with
Antegren and will discuss Biogen and
Antegren further in our Company
Analysis.
Other biotech companies are con-
tinuing on with the theme to block acti-
vated T cells from entering the lesions,
or by removing activated T cells alto-
gether from the CNS. For example, Ilex
Oncology (NASDAQ: ILXO) is cur-
rently in Phase II clinical trials evaluat-
ing Campath, a humanized monoclonal
antibody that depletes activated T and
B cells and modulates their activity. In
one small uncontrolled study, new
MRI lesion formation and relapses
were abolished for 18 months in pa-
tients treated with Campath. However,
half the patients continued to have
progression of disability and showed
evidence of continued atrophy of the
brain. The inability of Campath to con-
trol disability could be an indicator
that most immunomodulatory therapies
are unable to overcome damage to the
neurons, and may not be unique to
Campath. Alternatively, the B cells,
which were also depleted in the ther-
apy, may have rebounded afterwards
and resulted in an antibody-mediated
response that was responsible for the
disease progression. Additional stud-
ies are required to shed more light on
Campath before we can make any rec-
ommendation about the therapeutic
potential for the agent to be used for
MS.
Along these same lines, Protein
Design Labs (NASDAQ: PDLI) is
evaluating their humanized monoclonal
antibody, Zenapax, which targets the
IL-2 receptor on activated T cells as a
therapeutic agent for MS. The ration-
ale to use Zenapax as a therapeutic
agent for MS is relatively sound, as
only activated T cells express the IL-2
receptor on their cell surface. This fun-
