By Matthew Willett
Corixa Corp. released new data on its Melacine vaccine for Stage II melanoma, and though the statistical significance related to disease-free survival in the intent-to-treat population was lost with the inclusion of additional patients, a prospectively defined population of patients continued to exhibit statistically significant improvement in disease-free survival.
Separately, Corixa disclosed a multiyear antibody generation, screening and characterization agreement with Kirin Brewery Co. Ltd., of Tokyo, that gives Corixa access to Kirin¿s TC Mouse technology for antibody generation. The agreement, which includes an option for Corixa to get exclusive development and commercialization rights to resultant antibodies, calls for Kirin to receive license fees, milestone payments and royalties on product sales. Terms were not disclosed.
Seattle-based Corixa¿s Phase III Melacine trial, which dates to 1992, closed accrual in 1996, and initial results were reported after a predefined number of patients died or relapsed. Those data indicated Melacine had a statistically significant improvement on disease-free survival (p=0.04).
Corixa Chairman and CEO Steven Gillis said the new data will be included in the company¿s biologics license application (BLA) ¿ if Corixa files one for Melacine.
¿The first analysis was the final analysis from the protocol,¿ Gillis said. ¿In our discussions with the FDA they advised us if we were to go forward with the BLA we should include as up to date a data set as we possibly could. Therefore, they recommended that we obtain follow-up data on all patients still alive and being monitored in the study.¿
Now, including additional disease recurrence and morality data from as many patients as possible, the p value for disease-free survival has risen to above 0.05 ¿ not a statistically significant improvement.
But, Corixa said, in a patient population comprised of patients that express Class I major histocompatibility complex (MHC) human leukocyte antigen (HLA) A2 or C3 genes, Melacine does make a statistically significant improvement in disease-free survival (p=0.03).
That puts Corixa in unknown territory, eager to file for regulatory approval for a treatment that works for 60 percent to 70 percent of disease sufferers. Gillis said there¿s little precedent at the FDA for genetically tailored treatments.
¿Within the HLA A2- or C3-positive population is where it would appear the product has its greatest benefit,¿ Gillis told BioWorld Today. ¿This is a situation where we have the opportunity to tailor therapy based on the power of genomics, and that¿s what we¿re discussing with the FDA, whether they¿ll be supportive of us filing a BLA for this product restricted to those patients who express HLA A2 or C3.¿
Though genomics-inspired treatments for individuals according to their individual genetic structure are considered feasible, little in the way of regulatory proof of concept has been attempted, and the FDA¿s response to Corixa¿s Melacine could be the first time the agency has a chance to back a pharmacogenomics therapy.
¿A distant precedent could be the fact that Genentech¿s anti-HER-2/neu antibody [Herceptin] is only given to patients whose tumors express HER-2/neu,¿ Gillis said. ¿Patients are screened to see if they express that antigen, and if they do they qualify for therapy.¿
Now it¿s a waiting game for Corixa, which acquired Melacine through its 1999 merger with Ribi ImmunoChem Research Inc. Corixa acquired that company¿s 21 million outstanding shares for $56.3 million. (See BioWorld Today, June 11, 1999.)
Melacine is made of lysed (broken) cells from two human melanoma cell lines and combined with Corixa¿s proprietary Detox adjuvant. Detox adjuvant includes monophosphoryl lipid A adjuvant and mycobacterial cell wall skeleton, both of which activate the human immune system in the context of vaccination.
Corixa partners with Schering-Plough Corp., of Madison, N.J., for worldwide marketing of Melacine, and the companies currently are pursuing regulatory approval for the vaccine in Europe. Melacine was approved for sale in Canada in November 1999.
Gillis said Corixa will actively continue discussions with the FDA. He said the agency could indicate its receptiveness to a restricted-population BLA, its unwillingness to accept such a filing, or give the company no guidance. Gillis added he hopes to have a decision in the next three months.
¿The bottom line is that the data are positive because the p value is there,¿ Gillis said. ¿Whether the data are sufficiently positive to warrant filing is something that we will determine in concert with discussions with the FDA. You can¿t argue with the fact that the product has benefit on survival and relapse-free survival in these patients. That¿s what the data say.¿
Corixa¿s stock (NASDAQ:CRXA) dropped 36 cents Thursday, closing at $17.41.