A government panel Wednesday OK’d Corixa Corp.’s proposed design for a second Phase III trial for its melanoma vaccine, Melacine.
In the Phase III study, the Seattle-based company intends to measure overall survival as the primary endpoint in about 700 patients, Michelle Burris, Corixa’s senior vice president and chief financial officer, told BioWorld Today.
The company met with the FDA’s Oncologic Drugs Advisory Committee to discuss the extra study, and although the committee was not required to take an official vote, Burris said the general consensus was agreement with Corixa’s proposal. The panel agreed that the proposed second Phase III trial, in addition to the supportive data from the first Phase III trial, would be acceptable for approval of Melacine vaccine.
From here, Burris said, Corixa will work with the FDA, which has the final call on protocol approval. But Burris wasn’t sure when such a decision would be made, nor did she know when the second trial would begin.
Corixa’s stock (NASDAQ:CRXA) closed Thursday at $9.84, up 14 cents.
According to a research note released by Mark Monane, a research analyst at Needham & Company Inc. in New York, the second Phase III trial likely could take two to three years to enroll, and three to five years for follow-up. Commercialization is not likely to occur before 2005, Monane said.
Pending further discussion with the FDA, the protocol design is Melacine vs. observation in postsurgery Stage II melanoma patients, Burris said.
“We are encouraged by ODAC’s support of the data we presented and our current plans for a second Melacine Phase III trial,” Steven Gillis, Corixa’s chairman and CEO, said in a prepared statement. “We will work diligently with the FDA and national cooperative study groups to finalize this protocol and will continue to provide periodic updates as events warrant.”
Melacine is administered as a two-shot vaccination delivered in four six-month cycles, each consisting of 10 treatments followed by a three-week rest. It consists of lysed cells, derived from two human melanoma cell lines, combined with Corixa’s Detox adjuvant, which includes MPL adjuvant (monophosphoryl lipid A) and mycobacterial cell wall skeleton, both of which activate the human immune system in the context of vaccination.
Corixa acquired Melacine in 1999 through a $56.3 million stock-and-cash purchase of Hamilton, Mont.-based Ribi ImmunoChem Research Inc. (See BioWorld Today, June 11, 1999, and Oct. 8, 1999.)
Several months following completion and a final analysis of the original Phase III, the company learned from the FDA that an additional Phase III would be required.
The original Phase III study, called the Southwest Oncology Group trial (SWOG-9035), dates to 1992 when the vaccine was owned by Ribi. The controlled trial of 689 patients, randomized to either observation or Melacine therapy following surgical excision of their primary tumor, looked at the effects of Melacine vs. observation in Stage II melanoma patients. The primary endpoint, which was relapse-free survival, was missed in that trial, Burris said, but the secondary endpoints were strong. (See BioWorld Today, June 22, 2001.)
Re-analysis of the data showed that Melacine continued to provide an improvement in overall disease-free survival, but the statistical significance of that conclusion was lost. However, analysis of clinical benefit following completion of the data analysis in patients who were positive for expression of either Class I MHC HLA (human leukocyte antigen) A2 or C3 genes continued to show a highly statistically significant clinical benefit (p=0.005). And, Corixa’s analyses demonstrated a statistically significant improvement in overall survival in class I MHC HLA A2- or C3-positive patients who received Melacine vs. observation (p=0.003).
Corixa has partnered with Schering-Plough Corp., of Madison, N.J., for worldwide rights to Melacine. The product is approved in Canada.
Beyond Melacine, Corixa has a healthy pipeline with 16 programs in clinical development and 22 in preclinical development.
Furthermore, the company is anticipating word from the FDA around March 12 on the future of Bexxar (tositumomab and iodine 131 tositumomab), an investigational radioimmunotherapy being studied for the treatment of low-grade or transformed low-grade non-Hodgkin’s lymphoma. ODAC was scheduled to hear the Bexxar application in February but delayed the meeting due to the “extensive amount of material” submitted by the company. (See BioWorld Today, Jan. 11, 2002.)