Encouraging Data Presented on Oncophage(R) Vaccine at International Conference

Antigenics (NASDAQ: AGEN) today announced that data from a multi-center Phase 1/2 clinical trial of Oncophage (vitespen) for recurrent high-grade glioma (brain cancer) was presented at the International Conference on Brain Tumor Research and Therapy. The study was conducted by the Brain Tumor Research Center at the University of California, San Francisco (UCSF).

Data from 32 evaluable patients suggest that vaccination with Oncophage may improve overall survival in patients with recurrent high-grade glioma. An overall median survival of 44 weeks after tumor resection was observed. Approximately 70% of the evaluable patients survived beyond 36 weeks, and 41% survived up to or longer than one year. This is considered a significant achievement in the treatment of recurrent high-grade glioma. In addition, Oncophage was well tolerated, with no serious adverse events attributable to the vaccine.

Ivy Foundation Gives TGen $3M to Launch Genetic Brain Cancer Initiative

[July 16, 2008]

By Turna Ray

With a $3 million grant to the Translational Genomics Research Institute, the Ben and Catherine Ivy Foundation has launched an investigation into the gene patterns that could help researchers develop targeted drugs and diagnostics for brain cancer and allow doctors to personalize treatment for the disease.

The Ivy Foundation, a Palo Alto, Calif-based foundation that funds brain tumor research, kicked off the Ivy Genomics-Based Medicine Project last week. The project brings together nine US institutions: TGen, Ohio State University, MD Anderson Cancer Center, University of Alabama at Birmingham, University of California-San Francisco, Henry Ford Hospital, Mayo Clinic-Rochester Minnesota, Case Western Reserve University School of Medicine, and Van Andel Research Institute.

Under the GPM Project, these nine institutions will try “to better understand how the genetic differences in individual brain tumors can potentially inform the prediction of what will be the most effective treatment option for each patient,” the Ivy Foundation said in a statement.

Researchers will categorize brain tumors by molecular profiling for the first time and analyze tumor response to various treatments.

With the grant, TGen’s lead brain tumor researcher, Michael Berens, will coordinate and manage the two-stage project, which is expected to take between four and five years.

“Investigators hope to discover patterns within the genomic profiles that can be used to indicate tumor vulnerability to selected treatments,” a spokesperson for the Ivy Foundation told Pharmacogenomics Reporter this week. “The genomic profiles may also be exploited for development of novel targeted therapeutics for GBM.”

The Project

In the initial phase of the GBM Project, slated to start immediately, researchers at the nine institutions will genetically profile tumor tissue collected from 40 patients and grown in mice, and treat the animals with 20 marketed cancer drugs.

"Because of the collaborative nature of the project, researchers will now be able to compare results across institutions on a diverse set of tumors and treatment regimen response patterns.”

“At the end of testing, researchers will generate a catalog of 40 GBM fingerprints and the corresponding responses to each drug tested,” the foundation spokesperson said. This first stage is expected to take between one-and-a-half to two years.

Upon the successful completion of animal studies, the researchers will then move on to human trials. The treatments for testing are still being determined, according to the foundation spokesperson.

The GBM Project will profile tumor samples, looking at DNA amplification or deletion with microarray-based comparative genomic hybridization, gene promoter methylation of various genes including MGMT, and select genes for sequencing.

Studies have identified promoter methylation of the DNA repair gene MGMT as a genetic marker for response to standard therapy.

"Because of the collaborative nature of the project, researchers will now be able to compare results across institutions on a diverse set of tumors and treatment regimen response patterns,” TGen’s Berens said in the statement. “The size, scope, and potential impact this project will have for patients with brain cancer is simply huge."

Critical Need

The GBM Project evolved from founder Catherine Ivy’s experience helping her husband, Ben, battle brain cancer. Her husband’s struggle with the disease revealed the limited therapeutic options available to her husband and to other patients.

Ben, who was president of the Palo Alto-based investment advisory firm Ivy Financial Enterprises, died of brain cancer in 2005.

In memory of her husband, Catherine formed the Ivy Foundation to develop better diagnostics and targeted treatments what will increase survival and improve the quality of life for patients with brain tumors.

Currently, all patients with malignant brain tumors receive the standard of care, which usually consists of surgery, radiation, and chemotherapy with temozolomide. The standard of care in brain cancer does not take into account the genetic profile of the patient.

The GBM Project is the first brain project funded by the foundation. “In the fall, we will announce additional research projects that will be funded by the Ivy Foundation,” the foundation spokesperson said.

This year, the organization plans to grant $12 million to patient-focused research in brain cancer.

The American Brain Tumor Association estimates that 44,865 new cases of brain tumors, including benign and malignant tumors, will be diagnosed in 2008. More than 100,000 cancer patients in the US will experience symptoms due to a brain tumor in the spinal cord from cancer metastases.

UCSF Brain Tumor Vaccine Trial Shows Promising Results

A vaccine for treating a glioma, a recurrent cancer of the central nervous system that occurs primarily in the brain, has shown promise in preliminary data from a clinical trial at the University of California, San Francisco.

Findings from a group of 12 study patients showed that vitespen vaccination (trademarked as Oncophage) was effective in stimulating the patient’s immune system to attack the tumor cells, a function that is known medically as tumor-specific immune response. All the patients had recurrent, high-grade glioma, and all showed the immune response. The vaccine is made from the patient’s own tumor.

The clinical trial was conducted by the UCSF Brain Tumor Research Center. Results were presented April 16 at the 75th annual meeting of the American Association of Neurological Surgeons in Washington, DC.

“In this trial, we have observed a correlation between immune response as a result of Oncophage vaccination and potential clinical benefit,” said Andrew T. Parsa, MD, PhD, assistant professor in the Department of Neurological Surgery at UCSF and recipient of the 2007 Young Investigator Award at AANS. “We are encouraged by the prolonged improvement in overall survival rates, although this phase 1/2 study is not designed to primarily evaluate efficacy. The patients in this trial represent the most challenging patient population to treat.”

Of the 12 patients being treated, eight can currently be evaluated for overall survival, while four are still receiving treatment. Seven out of the eight patients have exceeded the historical median benchmark of 6.5 months survival from time of recurrence. The investigators will continue to follow the patients for overall survival. Based on these results, a larger, multi-center phase 2 study is planned for late 2007.

Derived from each individual’s tumor, vitespen contains the “fingerprint” of the patient’s particular cancer and is designed to reprogram the body’s immune system to target only cancer cells bearing this fingerprint. The vaccine is intended to leave healthy tissue unaffected and limit the debilitating side effects typically associated with traditional cancer treatments such as chemotherapy and radiation therapy. Vitespen has been granted fast-track and orphan drug designations from the Food and Drug Administration for both metastatic melanoma (skin cancer) and renal cell carcinoma (kidney cancer).

Reviewing the presentation at AANS, Henry Brem, MD, director of neurosurgery at the Johns Hopkins Medical Institutions, noted, “This is an encouraging study of a therapeutic cancer vaccine that targets multiple tumor antigens, supported by rigorous immuno-monitoring. A larger phase 2 trial is certainly warranted to evaluate efficacy.” Brem is a developer of the first approved local therapy for glioma.

The UCSF clinical trial is a phase1/2 study designed to establish the feasibility, safety and preliminary efficacy of vaccination in patients with recurrent, high-grade glioma. The trial involves two groups of six patients, both of whom receive a minimum of four injections. The first group receives biweekly vaccinations and the second receives weekly vaccinations. Patients are monitored for immune response before, during and after treatment.

The UCSF investigators will continue to follow patients for progression-free survival and overall survival. According to investigators, no adverse events or toxicity identified were considered attributable to the vaccine.

Cheryl Canagelo, a 52-year-old woman from Oakley, Calif., came to UCSF for a second opinion after undergoing radiation and chemotherapy elsewhere for treatment of a glioma. At UCSF she learned that part of the tumor was still present, and she enrolled in the vitespen vaccine trial.

Once the chemotherapy was out of her system, Parsa performed surgery, just four days before Christmas. He removed all but a very small amount of tumor that was near an area that could affect her speech. The removed tissue was sent to Antigenics, the Massachusetts biotech company that produces the vaccine from the patient’s tumor tissue. Altogether, Canagelo has now received seven injections of vaccine.

“My most recent MRI showed that there is no tumor,” Canagelo said. “I haven’t had any side effects from the treatment, and I’m getting stronger every day. I would urge patients to seek out second opinions and investigate clinical trials. I can tell you I am so glad I did.”

“Our goal is to change the management of recurrent glioma from a life threatening disease into a chronic disease with extended survival and improved quality of life for patients,” Parsa said. “Although our survival data are encouraging, a larger phase 2 study will be required to determine the benefit of vitespen for patients with recurrent glioma. The consistent, tumor specific immune response seen in these patients suggests that in the right patient population, the vaccine could have a significant impact.”

The clinical trial was funded by the American Brain Tumor Association and the National Cancer Institute’s Specialized Program of Research Excellence.

UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.