genetically modified a common herpes simplex virus strain (the kind that normally causes cold sores) to replicate inside tumors. Once inside, the treatment (OncoVex GM-CSF) is supposed to cause tumor cells to burst.
Coffin, in the grand scientific tradition of experimenting on members of one’s own team, apparently isolated the HSV-1 virus from a member of his lab, Perlmutter says. A clever modification was made so that it was “relatively selective” to replicate inside fast-dividing cells like cancer cells, Perlmutter says, and not so much in healthy tissues.
But that wasn’t really enough to make OncoVex into a cancer drug on its own, Perlmutter says. Next, Coffin and the BioVex team isolated one specific gene in the HSV-1 virus that plays a vital role in helping the virus to evade detection from immune system cells that might kill it. Once they found that gene, they deleted it in the new engineered virus—meaning that it couldn’t really hide anymore from the immune system. And, to top things off, BioVex engineered in the gene that makes a protein called GM-CSF, which more generally puts the immune system into a heightened state of alert, so it can mobilize against the modified virus it can now see as a troublemaker.
Do all three of those things, Perlmutter says, and “you get a profound anti-tumor response.”
Interesting as the science may be, no way would Amgen commit itself to a $1 billion payout without seeing some solid proof that this is actually helping patients in clinical trials. The data on this score is still preliminary, from a mid-stage clinical trial run by BioVex. As I noted in yesterday’s breaking news story, eight of the 13 initial responders with melanoma had their tumors completely disappear, and their responses were long-lasting. Although patients who entered the trial had terminal diagnoses, usually giving them six to nine months to live, more than half of the patients were alive after one year (58 percent) and two years (52 percent), according to data presented at the American Society of Clinical Oncology in June 2009. Side effects were mostly mild-to-moderate flu-like symptoms, researchers said.
Perlmutter noted yesterday that about 20 percent of the patients on the BioVex treatment went into complete remission, which was “very impressive.” Questions, of course, will remain about how long lasting the responses are, and how well this stacks up for melanoma patients. This is a notoriously tough malignancy to treat, but there has been some notable progress with other approaches in the past year—from Berkeley, CA-based Plexxikon, and New York-based Bristol-Myers Squibb.
One potential concern when injecting a live herpes simplex virus is whether it could cause a dangerous brain infection called encephalitis, Perlmutter says. He says he’s satisfied that BioVex has addressed this concern, through modifications that make it difficult for the virus to replicate in the brain. No cases of encephalitis have been seen in clinical trials, and it didn’t appear in animals even when the modified virus was injected directly into their brains.
But what really stood out for Perlmutter, again, was the immunology. Patients in the BioVex studies who had solid tumor masses saw shrinkage of those bulky masses when the new treatment was directly injected. That’s fine, but cancer doctors know that malignancies can spread fast and bounce back quickly to kill people even after an initial positive response. What struck Perlmutter as fascinating was not just that the directly injected tumors shrank, but that other tumors that had spread
