Roger Perlmutter, the guy who runs R&D at the largest biotech company in the world, is an immunologist by training. So it shouldn’t be any surprise that he’s fascinated by recent advances in which scientists have shown they can harness the immune system to fight tumors. Now he’s acting on that emerging knowledge of cancer immunology in a big way, through Amgen’s potential $1 billion acquisition of Woburn, MA-based BioVex.
Thousand Oaks, CA-based Amgen (NASDAQ: AMGN), which has significant R&D centers in South San Francisco, Seattle, and Cambridge, MA, made headlines yesterday with its big bet on a novel cancer treatment in development at BioVex. Perlmutter, the executive vice president of R&D at Amgen, has his fingerprints all over this deal, since he’s been working to transform Amgen into a more aggressive developer of anti-tumor drugs over the past decade. I’ve known Perlmutter for almost the entire time he’s been at Amgen, so I was eager to hear his thoughts the day after the big BioVex deal was struck.
Scientists have been dreaming for decades about alternatives to traditional chemotherapy, radiation, or surgery—particularly those that can harness the body’s immune system to fight tumors as if they were a foreign invader like a virus. Most of these efforts went down in flames, until Seattle-based Dendreon (NASDAQ: DNDN) won FDA approval last year for the first treatment of this kind—which analysts say now has multi-billion dollar annual sales potential. One variation on this theme is through what BioVex and others have done, utilizing what are known as oncolytic viruses. These viruses are designed to specifically replicate inside tumors, causing them to burst, while also sending signals that alert the immune system to seek and destroy any residual cancer cells that might have been able to evade the virus.
Neither BioVex, nor anybody else, has proven that it can fight tumors well enough to win FDA approval, but Amgen’s bet is that BioVex will validate the oncolytic virus approach much like Dendreon proved cancer immunotherapy a year ago.
“I’ve looked at this field for a long time and found it to be rather discouraging,” Perlmutter said of oncolytic viruses. But over the last couple of years, after seeing what BioVex has done in clinical trials, Perlmutter says he was impressed by not just the company’s engineered virus, but the immune system effect it was able to trigger. “It seemed to me it was more and more likely they were seeing an effective immune response. It looked more and more promising.”
BioVex has been pursuing this challenge for a long time, having been founded in 1999 by Robert Coffin, a virologist from University College London. A dozen years later, Amgen snapped it up as BioVex was pushing its lead program, OncoVex GM-CSF, through the third and final stage of clinical trials normally required for FDA approval. The company is enrolling patients with both melanoma, a deadly form of skin cancer, and head and neck cancer.
The science is really interesting here, and Perlmutter was clearly happy to talk about what interested him (maybe he was bored with poring over spreadsheets on yesterday’s earnings call?).
Here’s the basic idea. The BioVex team has 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 to other parts of the body also shrank, even when they weren’t directly injected.
“You can’t make those tumor masses go away by chance. Something happened here. That tells you that there’s an immune response having an effect,” Perlmutter says. “The question is how many responses we’ll see, which patients it happens for, how durable the responses are, and how meaningful that is for a new therapy for cancer.”
Amgen has been busy lately with its own internally developed antibody for cancer patients, denosumab (Xgeva), which was recently approved for treating bone-related tumors. It has quite a few other biotech drug approaches moving ahead in its pipeline. But it didn’t have a program like BioVex’s, and BioVex, naturally, doesn’t have anywhere near the horsepower of Amgen (which had a jaw-dropping $17.4 billion in cash on its books heading into 2011).
Having that much cash, and an armada of people whose job is to run Phase III clinical trials that will satisfy the FDA, means this little BioVex drug will get a lot more oomph behind it than ever before.
After looking over the BioVex results, Perlmutter says he talked to Coffin and others at BioVex about working together. Resources, which are always hard to come by for venture-backed biotech companies, was the big card he had to play. “We can bring to this company the kind of resources it would really need to do effective large-scale clinical trials,” Perlmutter says. “Not to discredit what they have already achieved, which is considerable. But we have a bit more muscle.”
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