More on Zevalin
Merrill just issued a report on Zevalin which has some relevance to those following CLTR. Any comments will be appreciated.
"IDEC Pharmaceuticals Corp. ? 23 November 1999
Robust Zevalin Data
The top-line results of the interim analysis of the phase III trial comparing Zevalin to Rituxan are available. Of the 143 patients enrolled with relapsed low-grade and/or bulky Non-Hodgkin?s lymphoma, the first 90 patients are used for the interim analysis. Patients were randomized to
receive either 4 doses of Rituxan alone or 2 doses of
Rituxan plus 1 dose of Zevalin. The data demonstrate that
Zevalin achieved a robust 80% response rate in low-grade
relapsed or bulky-disease Non-Hodgkin?s lymphoma
patients. The 44% response rate for Rituxan seen in the
trial confirms the response rate seen in the previous
Rituxan trials.
Zevalin is IDEC?s second antibody product for the
treatment of Non-Hodgkin?s lymphoma. It is an anti-CD20
antibody attached to the radioactive isotope
Yttrium-90. In clinical practice, we continue to expect that
Rituxan will be used ahead of Zevalin. Rituxan is safer
and easier to use in the doctor?s office, whereas the patient has to be referred to a medical center with nuclear
medicine capabilities in order to receive Zevalin.
Street Concerns
There have been two concerns regarding the Zevalin
abstract - Did Rituxan perform well enough and does
Zevalin cause excess neutropenia?
Regarding Rituxan, most of the prior clinical data with
four doses of Rituxan alone has shown a response rate of
45-50% in relapsed NHL patients; with 6 doses the
response rate reaches 60%. For patients with bulky
disease, Rituxan alone achieves a 30% response rate. In
the Zevalin vs. Rituxan study, 22% of Rituxan treated
patients had bulky disease, which reduces the average
response rate of Rituxan to that seen in this trial.
Secondly, it appears the Zevalin causes more neutropenia
than Coulter?s Bexxar. However IDEC uses a more
stringent definition of neutropenia than Coulter. If a
patient?s neutrophil count falls below 500/ml, IDPH called
this neutropenia, whereas Coulter used a limit of 100/ml
for neutropenia. In addition, Zevalin was dosed to the
point where patients started to develop neutropenia in-order
to maximize the therapeutic benefit. Furthermore,
with the availability of Neupogen, neutropenia is no longer
a major clinical concern. In the Zevalin trial, there were
no infectious adverse events.
Thus, Zevalin has been shown to be very safe, with a
highly statistically significant benefit in the interim
analysis. The trial should be complete by the middle of
next year and the drug should be launched in the U.S. in
early 2001." |
