11
also expected later this year.
The company reiterated its inten-
tion to partner Velcade sometime in
2003.
Millennium's developmental time-
line is on track and investors are gravi-
tating to its story. Meanwhile, inves-
tors are wondering which drug has the
advantage in treating patients with
multiple myeloma. Will it be Millen-
nium's Velcade or Celgene's Thalomid
or Revimid?
Currently, Thalomid is being pre-
scribed by physicians as an off-label
use to treat multiple myeloma. Thalo-
mid has not been approved by the
FDA as a therapy for multiple myeloma
or any other cancers. However, given
physicians' relatively greater experi-
ence with Thalomid in multiple my e-
loma, Thalomid could be used first and
Velcade later on in patients who have
failed Thalomid. Based on clinical data
to date, patients who have failed Tha-
lomid have responded to Velcade or
Revimid. In addition, there is anecdotal
evidence from investigators that pa-
tients who failed Velcade have re-
sponded to Revimid and vice-versa.
To date, the clinical experience does
support the sequential use of any
these drugs.
Alternatively, as proposed by in-
vestigators, Velcade could be used in
combination with either Thalomid or
Revimid, given their different mecha-
nisms of action. Data from a pilot
study evaluating the safety of Velcade
plus Thalomid was presented at the
last ASH meeting. There were no syn-
ergistic toxicities in the trial and further
studies with the combination will be
conducted.
The available data to-date, does
not indicate a clear winner among Tha-
lomid, Velcade and Revimid, although
future data may support a different
conclusion. Even if response rates
continue to be comparable among the
three drugs with additional trials, other
factors that may differentiate the three
BioTech Stock Report, March 2003
ple myeloma.
The U.S. submission is based on
the recently completed Phase II study
(the SUMMIT trial) which was pre-
sented at the last American Society of
Hematology (ASH) meeting in Decem-
ber. Assuming the six-month priority
review goes well, Velcade could be on
the market in the second half of 2003,
at least 12 to 18 months sooner than if
the company were to rely on its ongo-
ing Phase III trial for approval.
Millennium's strategy of filing a
NDA based on a surrogate end point
(tumor response rates measured by
drops in paraprotein) in a phase II trial
is aggressive. Although approval is
certainly possible, the hurdles are
high. Even though the efficacy results
seem convincing at face value, addi-
tional critical issues for approval will
be whether the SUMMIT trial was ade-
quately designed and conducted. If
the FDA accepts the application for
filing that will be an indirect indication
that the study was reasonably well
conducted, since it will suggest the
data set has no major deficiencies. The
FDA's decision will be known within
60 days of the NDA submission; that
is, by mid-March. Afterwards, it is
more than likely, Velcade will be the
subject of an Oncologic Drugs Advi-
sory Committee (ODAC) advisory
panel in the second quarter of 2003,
and could win accelerated approval in
the third quarter of 2003. Given re-
lapsed/refractory multiple myeloma
patients have few treatment options,
we believe Millennium has a reason-
able chance of receiving accelerated
approval for Velcade.
As a component of Millennium's
drive to profitability, the company is
counting on sales of Velcade in multi-
ple indications. The company is ex-
pecting to present results from a Phase
II study in CLL this year, and it re-
cently began trials in colorectal and
non-small cell lung cancer. Further
studies in ovarian cancer and NHL are
idiopathic thrombocytopenic purpura,
systemic lupus erythematosis). Some
near-term deceleration in growth is
likely, as Rituxan becomes a victim of
its own success. The drug has already
penetrated 60+% of the combined NHL
and CLL markets and some indications
such as front-line aggressive NHL are
now 80+% penetrated.
Zevalin has provided a modest
contribution to the bottom line. The
slower than anticipated sales could be
due to reimbursement, identification of
NHL patients suitable for therapy, and
lack of coordination between physi-
cians and pharmacists. All are signifi-
cant hurdles. Nonetheless, physicians
and pharmacists have a positive opin-
ion of Zevalin. Nuclear medicine physi-
cians strongly believe that Zevalin is a
safe and efficacious therapy and nu-
clear pharmacists expressed a very
high degree of interest in Zevalin.
With physician education and training
now nearly complete, if so, familiarity
will be the most important factor in
driving Zevalin out of the salvage set-
ting and into second-or third-line use.
Meanwhile, a competitor of
Zevalin is Bexxar, planned to be in the
U.S. market later this year, provided it
gets FDA approval in early May.
Corixa plans to price Bexxar similar to
Zevalin, about $17,000 per dose. But
IDEC has filed a lawsuit against Corixa
and GlaxoSmithKline for patent in-
fringement in connection with Corixa's
Bexxar and its use in the treatment of
NHL. No doubt IDEC is trying to slow
down the comp etition and align
Zevalin as the choice of therapy.
Millennium/NASDAQ: MLNM
(BSR#3: Prostate Cancer) filed an
NDA with the FDA seeking acceler-
ated approval for Velcade in relapsed/
refractory multiple myeloma, and the
company has recently announced that
European regulators accepted the Mar-
keting Authorization Application
(MAA) filing for Velcade to treat multi-
