Glioblastoma Vaccine to Be Tested as Orphan Drug, Easing Clinical Trials Process


The designation recognizes that the vaccine, an immunotherapy called SurVaxM, would treat a rare disease, defined as one that affects a patient population of less than 200,000 Americans. However, because it acts on a protein that appears in 80 percent of cancers generally, SurVaxM may have wider applications.

A vaccine for glioblastoma — a form of brain cancer – has received orphan drug designation from the FDA, which could make it easier for scientists to test the treatment in clinical trials.

The designation recognizes that the vaccine, an immunotherapy called SurVaxM, would treat a rare disease, defined as one that affects a patient population of less than 200,000 Americans. The vaccine’s developers hope this means that the required size of phase 3 trials of SurVaxM will be smaller than for drugs designed to treat non-rare diseases because of the small pool of possible study participants and the lack of effective treatments for glioblastoma.

“We hope that would speed up phase 3 clinical trials, simply by reducing the patient load that we would have to accumulate,” said co-inventor Michael Ciesielski, Ph.D., assistant professor of neurosurgery at Roswell Park Cancer Institute and chief scientific officer at MimiVax, the Roswell Park spinoff company producing and testing the vaccine.

Although the orphan drug designation does not guarantee FDA approval, it does indicate a vetting of the drug by the FDA which ended favorably.

SurVaxM was developed at Roswell Park, one of five institutions where phase 2 trials of the drug are being conducted. The vaccine’s other co-inventor is Robert Fenstermaker, M.D., chair of neurosurgery at Roswell Park and chief medical officer at MimiVax.

How SurVaxM Works

SurVaxM boosts the immune system’s ability to attack the protein survivin, whose activity otherwise contributes to cancer’s resistance against treatments such as chemotherapy and radiotherapy. Survivin is found in over 90 percent of glioblastoma cases. It is also present in most other kinds of cancerous tumors, so further research may find that SurVaxM’s application extends beyond patients with glioblastoma.

Survivin is normally only found in early childhood and the developing fetus, but has harmful effects when it contributes to the growth of cancerous tumors. It’s “a stress protein that tumor cells have tapped into to allow them to continue to divide longer than they should,” Ciesielski explains. “It prevents cells from turning on their programmed cell death pathway.”

Administered by injection, the medication releases a peptide molecule to which the immune system responds by producing antibodies and T cells. Ciesielski said that this causes a cross reaction against the survivin protein found in the tumors. This means that the response the immune system sends to attack the peptide molecule will also target survivin, which the immune system often fails to respond to. He said that SurVaxM’s response is a multifaceted one, somewhat rare among peptide vaccines: “Many of these vaccines either generate an antibody response only or a T-cell response only. There are not a lot that get both, which is what we’re seeing from this one.”

The vaccine would be administered as part of the typical treatment process. In a phase 1 trial of patients with recurrent glioblastoma, it was injected just after the tumor was removed. In this trial, most patients developed immune responses to survivin. Three of eight evaluable patients had stable disease 12 months after starting the treatment, and no drug-related side effects beyond those deemed mild or moderate occurred.

In the ongoing phase 2 trials, the vaccine is being administered to newly diagnosed patients, who receive it after surgery and radiation, but before chemotherapy treatment. The purpose of the phase 2 studies is to determine whether SurvVaxM has any impact on the effectiveness of the most common glioblastoma chemotherapy drug, temozolomide, in treating tumors.

Because phase 2 trials are still underway, Ciesielski was unable to offer details except that an interim analysis had concluded that the trials should continue. This suggests that SurVaxM has not detracted from the effectiveness of chemotherapy treatment in these patients.

A Potential Treatment for Additional Cancer Types

Ciesielski also noted his hope that glioblastoma would not be the only cancer to which the new drug would be applicable. Survivin, he said, “is expressed in about 80 percent of all other cancers: prostate, ovarian, breast, leukemia,” making SurVaxM “more of a cancer vaccine at this point. We are looking at it in the glioblastoma world because that’s where our training and background is, being in neuro-oncology. We have to start somewhere, but it’s something we’d like to see applied to many cancers.”

At present, for instance, clinical trials are underway to determine the effect of the vaccine on multiple myeloma.

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