Corixa provides update on late stage clinical programs
06/20/2001
Results of year 2000/2001 data follow-up for previously completed pivotal trial of Melacine
vaccine vs. observation in post-surgery, Stage II melanoma patients
Dialogue With FDA regarding possibility of accelerated approval of Melacine in patients with
specific HLA gene expression
Progress of response to FDA complete review letter for Bexxar BLA
Seattle, June 20, 2001 – Corixa Corporation (Nasdaq: CRXA), a developer of
immunotherapeutics, today announced the completion of its year 2000 to May 2001 data sweep
associated with its completed pivotal trial of Melacine® vaccine for Stage II melanoma.
The results of this study -- conducted under a former Ribi ImmunoChem Research, Inc. (now
Corixa) investigational new drug application (IND) -- were initially reported by the Southwest
Oncology Group (SWOG) in March 2000. The study examined the effects of Melacine vaccination
vs. observation in a randomized, controlled trial of 689 Stage II melanoma patients. Patients in
the study were randomized to either observation or Melacine therapy following surgical excision of
their primary tumor. Surgery results in cure of more than 55 percent of patients with Stage II
melanoma, whereas the remainder of the population will relapse. The study closed to accrual in
1996 and initial results were reported when a pre-defined number of events (death or disease
recurrence) occurred. Analysis of the data in March 2000 revealed a statistically significant
(p=0.04) improvement in disease free survival in favor of Melacine treatment in the intent to treat
population (689 patients). A prospectively defined, secondary analysis of the interaction between
specific Class I Major Histocompatability Complex (MHC) genes and the product’s efficacy also
showed a highly statistically significant improvement in disease free survival in patients who
expressed either Class I MHC human leukocyte antigen (HLA) A2 or C3 genes (p=0.005). The
expression of these immune response genes was previously noted to be associated with beneficial
clinical response to Melacine treatment in Phase I and II clinical trials. HLA genes encode
proteins that are intimately involved in antigen recognition and immune cell activation and
function.
In an effort to provide the U.S. Food and Drug Administration (FDA) and its advisory panel
reviewers with as up-to-date a data package as possible, Corixa committed to obtain additional
mortality and disease recurrence data on as many patients as possible in the database, prior to
proceeding with completion of a Biologics License Application (BLA) filing.
Twenty-seven new events have been noted in the time frame between the trial’s final analysis by
SWOG and the recent data sweep, of which 18 occurred in the Melacine arm, and nine occurred
in the observation arm. Re-analysis of overall disease free survival including these new data,
shows that Melacine continues to provide an improvement in overall disease free survival,
although the statistical significance of that conclusion has been lost with a convergence of the
resultant disease free survival curves (p>0.05).
However, analysis of clinical benefit following completion of the data sweep in patients who were
positive for expression of either Class I MHC HLA A2 or C3 genes continues to show a highly
statistically significant clinical benefit of Melacine vs. observation in terms of increased disease
free survival (p=0.005). Furthermore, Corixa’s analyses demonstrated a statistically significant
improvement in overall survival in class I MHC HLA A2 or C3 positive patients that received
Melacine vs. observation (p=0.003). Expression of either MHC HLA A2 or C3 in the absence of
Melacine vaccination was of no clinical benefit to patients, indicating that simple expression of
particular MHC haplotypes is not a prognostic factor for positive outcome in this group of patients
in the absence of treatment.
“Given the results of the data sweep, we have begun a discussion with FDA regarding the
advisability of filing a BLA for accelerated approval of Melacine in patients that express either
Class I MHC HLA A2 or C3 genes,” stated Steven Gillis, Ph.D., chairman and chief executive
officer of Corixa. “Under such a scenario, if approved, Corixa would commit to conducting a
confirmatory trial of Melacine vaccine in A2/C3 positive melanoma patients, and perhaps in
patients with more advanced disease. We have entered the post-genomic world where one of the
outcomes of the genomic revolution is that patient responses to therapies can and should be
tailored to the patient’s genetic capabilities to respond to such treatments. Patient response to
Melacine would appear to be linked to particular MHC genes. MHC genes, often called immune
response genes, are highly variable (polymorphic) from individual to individual and are known to
be responsible for many of the differences observed in immune responses between individuals.”
Gillis added, “The opportunity to provide survival benefit to Stage II melanoma patients as a
result of vaccination of individuals that express specific immune response genes makes both
scientific and clinical sense. Given that Class I MHC HLA A2 or C3 genes are expressed in
between 60 and 70 percent of the U.S. population, this approach could provide clinical benefit to
a significant number of cancer patients. We hope that FDA will be supportive of such a regulatory
strategy. Once we have had an opportunity to complete our dialogue with the agency, we will
determine whether such a filing would be in the best interests of Corixa.”
“In addition to Melacine discussions with the FDA, we are making excellent progress on the
completion of responses to questions raised by FDA in its complete review letter of March 16,
2001 concerning Bexxar™. Answers to many questions are now complete and we are focused on
finishing final study reports for two of the three additional studies that we previously announced
would be submitted to the agency in response to the complete review letter. The majority of this
work is also completed and we are awaiting the results of independent radiology and oncology
reviews of response and duration of response data. These reviews have been ongoing and are
now nearing completion. We will file our response with the agency when the independent review
data is final. We do not expect to provide further updates until we file our response to the
complete review letter with FDA.”
About Melanoma and Melacine
Malignant melanoma is a highly metastatic and lethal form of skin cancer. It is the most common
form of cancer in women between the ages of 25-29 and the second most common form of cancer
in women ages 30-34. It is the third most common form of cancer in men ages 35-44. According to
the American Cancer Society, cancer of the skin is the most common of all cancers. Melanoma
accounts for about 4 percent of skin cancer cases, but causes about 79 percent of skin cancer
deaths. The number of new cases of melanoma found in the United States is on the rise. The
American Cancer Society predicts that, in the year 2001, there will be close to 50,000 new cases
of melanoma in the United States and about 8,000 deaths resulting from melanoma.
Melacine melanoma vaccine consists of lysed (broken) cells from two human melanoma cell lines
combined with Corixa's proprietary Detox® adjuvant. Detox adjuvant includes MPL® adjuvant
(monophosphoryl lipid A) and mycobacterial cell wall skeleton, both of which activate the human
immune system in the context of vaccination. Melacine, MPL and Detox were acquired by Corixa
as part of its purchase of Ribi ImmunoChem Research, Inc., in October 1999. Melacine is
approved for sale in Canada for the treatment of Stage IV melanoma..... |
